Clinical Trials

MainTitle

Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current Antiretroviral Regimen in Virologically Suppressed HIV-1-infected Adults

This study is ongoing, but not recruiting participants.
Sponsor
ViiV Healthcare

Collaborator
Janssen Pharmaceuticals
GlaxoSmithKline

Information provided by (Responsible Party)
ViiV Healthcare
ClinicalTrials.gov Identifier
NCT02951052

First received: September 15, 2016
Last updated: September 10, 2018
Last Verified: September 2018
History of Changes
Purpose

Purpose

The Antiretroviral Therapy as Long Acting Suppression (ATLAS) study is being conducted to establish if human immunodeficiency virus type-1 (HIV-1) infected adult subjects with current viral suppression on a regimen with 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus a third agent, remain suppressed upon switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). This is a Phase 3, multi-phase, randomized, open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1, antiretroviral therapy (ART)-adult subjects who are stably suppressed on a current antiretroviral (ARV) regimen. This study is designed to demonstrate the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks (Q4W: monthly) compared with maintenance of current ARV regimen containing 2 NRTIs plus an INI, NNRTI, or a PI. Eligible subjects will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue current ART or switch to initiate oral therapy with CAB 30 mg + RPV 25 mg once daily for 4 Weeks followed by Q4 weekly (monthly) CAB LA + RPV LA injections. Following the Maintenance phase at Week 52, subjects who were randomized to continue their current ART regimen will be given an option to switch to CAB LA + RPV LA injections. Those subjects would transition to LA dosing, beginning with 4 weeks oral CAB + RPV therapy at Week 52, and receive the first IM CAB LA + RPV LA injections at Week 56.

Condition Intervention Phase
Infection, Human Immunodeficiency Virus

Drug : Cabotegravir (CAB) tablet
Drug : Rilpivirine (RPV) tablet
Drug : Cabotegravir - Injectable Suspension (CAB LA)
Drug : Rilpivirine - Injectable Suspension (RPV LA)
Drug : 2 NRTIs plus an INI, NNRTI, or PI
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Randomized, Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-acting Cabotegravir Plus Long-acting Rilpivirine From Current INI- NNRTI-, or PI-based Antiretroviral Regimen in HIV-1-infected Adults Who Are Virologically Suppressed

Further study details as provided by ViiV Healthcare:

Primary Outcome Measures

  • PROPORTION OF SUBJECTS WITH PLASMA HIV 1 RIBONUCLEIC ACID (RNA) >=50 COPIES/MILLILITRE (C/ML) AT WEEK 48 [ Time Frame: Week 48 ]
    Proportion of subjects with a virologic failure analyzed by Food and Drug Administration (FDA) Snapshot algorithm for the Intent-to-Treat Exposed population (subjects randomized and receiving at least one dose of investigational product during the Maintenance Phase)
Secondary Outcome Measures:
  • PROPORTION OF SUBJECTS WITH PLASMA HIV-1 RNA <50 COPIES/ML (C/ML) [ Time Frame: Week 48 ]
    Assessed using the FDA Snapshot algorithm at week 48. It is a key secondary endpoint
  • PROPORTION OF SUBJECTS WITH PLASMA HIV-1 RNA <200 C/ML [ Time Frame: Week 48 ]
    Assessed using the Snapshot algorithm at week 48
  • PROPORTION OF SUBJECTS WITH CONFIRMED VIROLOGIC FAILURE [ Time Frame: Week 48 ]
    Two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to <200 c/mL. Assessed at week 48
  • CHANGE FROM BASELINE IN PLASMA HIV-1 RNA [ Time Frame: Baseline and Week 48 ]
    Analyzed at week 48
  • CHANGES FROM BASELINE IN CD4+ CELL COUNTS [ Time Frame: Baseline and Week 48 ]
    Analyzed at week 48
  • INCIDENCE OF DISEASE PROGRESSION [ Time Frame: Up to Week 48 ]
    Assessed by HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death over 48 weeks
  • NUMBER OF SUBJECTS WITH ADVERSE EVENTS (AES) AND SERIOUS ADVERSE EVENTS (SAE) [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
  • SEVERITY OF AES [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
  • NUMBER OF SUBJECTS WITH ABNORMAL LABORATORY PARAMETERS [ Time Frame: Up to Week 48 ]
    Incidence and severity will be analyzed at Week 48
  • SEVERITY OF LABORATORY ABNORMALITIES [ Time Frame: Up to Week 48 ]
    Laboratory abnormalities will be automatically graded by the central lab according to the Division of AIDS toxicity scales
  • PROPORTION OF SUBJECTS WHO DISCONTINUE TREATMENT DUE TO AES [ Time Frame: Up to Week 48 ]
    Subjects who discontinue treatment due to AEs will be analyzed
  • NUMBER OF SUBJECTS HAVING CHANGES IN LABORATORY PARAMETERS [ Time Frame: Up to Week 48 ]
    Laboratory parameters includes; 1. Hematology parameters-platelet count, red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscular volume, WBC differential (includes; neutrophils, lymphocytes, monocytes, eosinophils and basophils), 2. Clinical chemistry- blood urea nitrogen, creatinine, fasting glucose, sodium, potassium, chloride, total carbon dioxide, lipase, aspartate aminotransferase , alanine aminotransferase, alkaline phosphatase, phosphate, total bilirubin, albumin, creatine phosphokinase, creatinine clearance will be analyzed over Week 48
  • CHANGE FROM BASELINE IN FASTING LIPIDS [ Time Frame: Baseline and up to Week 48 ]
    Total cholesterol, high density lipoprotein, low density lipoprotein, and triglycerides will be analyzed
  • CHANGE FROM BASELINE IN FASTING LIPIDS [ Time Frame: Baseline and up to Week 96 ]
    Total cholesterol, high density lipoprotein, low density lipoprotein, and triglycerides will be analyzed
  • NUMBER OF SUBJECTS WITH TREATMENT EMERGENT RESISTANCE [ Time Frame: Week 48 ]
    Genotypic and phenotypic resistance to CAB, RPV, and other on-study antiretroviral treatment (ART) at Week 48
  • PROPORTION OF SUBJECTS WITH VIROLOGIC FAILURE AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Week 48 ]
    Assessed using the FDA Snapshot algorithm at week 48.
  • PROPORTION OF SUBJECTS WITH PLASMA HIV-1 RNA <50 C/ML AS A MEASURE OF EFFICACY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Week 48 ]
    Assessed using the FDA Snapshot algorithm at week 48
  • NUMBER OF SUBJECTS WITH AES AND SAES AS A MEASURE OF SAFETY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. Incidence and severity will be analyzed at Week 48
  • SEVERITY OF AES AS A MEASURE OF SAFETY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as serious adverse event (SAE). Incidence and severity will be analyzed at Week 48
  • NUMBER OF SUBJECTS WITH ABNORMAL LABORATORY PARAMETERES AS A MEASURE OF SAFETY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    Incidence and severity will be analyzed at Week 48
  • SEVERITY OF LABORATORY ABNORMALITIES AS A MEASURE OF SAFETY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    Laboratory abnormalities will be automatically graded by the central lab according to the Division of AIDS toxicity scales
  • PROPORTION OF SUBJECTS WHO DISCONTINUE TREATMENT DUE TO AES AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    Subjects who discontinue treatment due to AEs will be analyzed
  • NUMBER OF SUBJECTS HAVING CHANGES IN LABORATORY PARAMETERS AS A MEASURE OF SAFETY AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    Laboratory parameters includes; 1. Hematology parameters-platelet count, red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscular volume, WBC differential (includes; neutrophils, lymphocytes, monocytes, eosinophils and basophils), 2. Clinical chemistry- blood urea nitrogen, creatinine, fasting glucose, sodium, potassium, chloride, total carbon dioxide, lipase, aspartate aminotransferase , alanine aminotransferase, alkaline phosphatase, phosphate, total bilirubin, albumin, creatine phosphokinase, creatinine clearance will be analyzed over Week 48
  • NUMBER OF SUBJECTS WITH TREATMENT EMERGENT RESISTANCE AS PER BASELINE THIRD AGENT TREATMENT CLASS [ Time Frame: Up to Week 48 ]
    Genotypic and phenotypic resistance to CAB, RPV, and other on-study antiretroviral treatment (ART) at Week 48
  • PLASMA TROUGH CONCENTRATION (CTROUGH) FOR CAB LA [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
  • PLASMA TROUGH CONCENTRATION (CTROUGH) FOR RPV LA [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41. ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
  • MAXIMUM CONCENTRATION (CMAX) IN PLASMA FOR CAB LA ARM [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
  • MAXIMUM CONCENTRATION (CMAX) IN PLASMA FOR RPV LA ARM [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
  • PLASMA AREA UNDER THE CONCENTRATION-TIME CURVE (AUC) FOR CAB LA [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
  • PLASMA AREA UNDER THE CONCENTRATION-TIME CURVE (AUC) FOR RPV LA [ Time Frame: Pre-dose at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, and 96; 2 hours post-dose at Weeks 4, 48 and 96; 1 week post-dose at Weeks 5 and 41 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
  • NUMBER OF SUBJECTS WITH DIFFERENT DEMOGRAPHIC PARAMETERS FOR INTER-SUBJECT VARIABILITY [ Time Frame: Up to Week 96 ]
    Demographic parameters including, but not limited to, age, sex, race, body weight, body mass index, and relevant laboratory parameters will be evaluated as potential predictors of inter subject variability for pharmacokinetic parameters.
  • PROPORTION OF SUBJECTS WITH PLASMA HIV-1 RNA <50 COPIES/ML (C/ML) DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Assessed using the FDA Snapshot algorithm up to week 96.
  • PROPORTION OF SUBJECTS WITH CONFIRMED VIROLOGIC FAILURE DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Two consecutive plasma HIV-1 RNA levels ≥200 c/mL after prior suppression to <200 c/mL. Assessed up to week 96.
  • CHANGE FROM BASELINE IN PLASMA HIV-1 RNA DURING EXTENSION PHASE [ Time Frame: Baseline and up to Week 96 ]
    Analyzed up to Week 96
  • CHANGES FROM BASELINE IN CD4+ CELL COUNTS DURING EXTENSION PHASE [ Time Frame: Baseline and up to Week 96 ]
    Analyzed up to Week 96
  • INCIDENCE OF DISEASE PROGRESSION DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Assessed by HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death up to Week 96
  • NUMBER OF SUBJECTS WITH AES AND SAES DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. Incidence and severity will be analyzed at Week 48
  • SEVERITY OF AES DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as serious adverse event (SAE).
  • NUMBER OF SUBJECTS WITH ABNORMNAL LABORATORY PARAMETERS AS A MEASURE OF SAFETY DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Incidence and severity will be analyzed at Week 96
  • SEVERITY OF LABORATORY ABNORMALITIES AS A MEASURE OF SAFETY DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Laboratory abnormalities will be automatically graded by the central lab according to the Division of AIDS toxicity scales
  • PROPORTION OF SUBJECTS WHO DISCONTINUE TREATMENT DUE TO AES DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Subjects who discontinue treatment due to AEs will be analyzed
  • NUMBER OF SUBJECTS HAVING CHANGES IN LABORATORY PARAMETERS DURING EXTENSION PHASE [ Time Frame: Up to Week 96 ]
    Laboratory parameters includes; 1. Hematology parameters-platelet count, red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscular volume, WBC differential (includes; neutrophils, lymphocytes, monocytes, eosinophils and basophils), 2. Clinical chemistry- blood urea nitrogen, creatinine, fasting glucose, sodium, potassium, chloride, total carbon dioxide, lipase, aspartate aminotransferase , alanine aminotransferase, alkaline phosphatase, phosphate, total bilirubin, albumin, creatine phosphokinase, creatinine clearance will be analyzed over Week 48
  • NUMBER OF SUBJECTS WITH ACCEPTANCE OF INJECTION-RELATED PAIN AND INJECTION SITE REACTIONS (ISRS) (FOR CAB LA + RPV LA) [ Time Frame: Up to Week 96 ]
    The Perception of iNjection questionnaire (PIN) will be used to assess the following dimension scores: Bother of ISRs, Leg movement, Sleep, and Injection Acceptance. Additionally, individual PIN item scores will assess pain during injection, anxiety before and after injection, willingness to be injected in the future and overall satisfaction with mode of administration over time. PIN will be assessed at weeks 5, 41, 48, 96 and/or Withdrawal .Key secondary endpoints include the proportion of subjects considering pain and local reactions following injection to be extremely or very acceptable based on the acceptability score after first injection and over time, and changes in the PIN acceptance score within the CAB LA + RPV LA arm over time
  • CHANGE FROM WEEK 5 IN DIMENSION SCORES USING THE PERCEPTION OF INJECTION QUESTIONNAIRE (PIN) [ Time Frame: Week 5 to Week 96 ]
    The Perception of iNjection questionnaire (PIN) will be used to assess the following dimension scores: Bother of ISRs, Leg movement, Sleep, and Injection Acceptance. Additionally, individual PIN item scores will assess pain during injection, anxiety before and after injection, willingness to be injected in the future and overall satisfaction with mode of administration over time. PIN will be assessed at weeks 5, 41, 48, 96 and/or Withdrawal .Key secondary endpoints include the proportion of subjects considering pain and local reactions following injection to be extremely or very acceptable based on the acceptability score after first injection and over time, and changes in the PIN acceptance score within the CAB LA + RPV LA arm over time
  • CHANGE FROM BASELINE IN HEALTH RELATED QUALITY OF LIFE (HRQOL) [ Time Frame: Baseline and up to Week 96 ]
    HIV/AIDS-targeted quality of life questionnaire (HAT QoL) will be assessed
  • CHANGE FROM BASELINE IN TOTAL TREATMENT SATISFACTION [ Time Frame: Baseline and up to Week 96 ]
    The HIV Treatment Satisfaction Questionnaire-status-12 (HIVTSQs-12) will be used to assess the "Total Treatment Satisfaction" score as well as the following sub-scale scores: "pain/discomfort" and "ease of administration. HIVTSQs-12 will be assessed at Baseline (Day 1) and weeks 4b, 24, 44, 96 and/or WD.
  • CHANGE IN TREATMENT SATISFACTION OVER TIME [ Time Frame: Baseline and up to Week 48 ]
    The HIV Treatment Satisfaction Questionnaire-change-12 (HIVTSQc-12) will be used to assess the "Total Treatment Satisfaction" score as well as the following sub-scale scores: "pain/discomfort" and "ease of administration. It will assessed at week 96 and/or WD
  • CHANGE FROM BASELINE IN HEALTH STATUS [ Time Frame: Baseline and up to Week 96 ]
    Overall health status will be assessed with the 12-item Short Form Health Survey (SF-12) as well as the Physical and Mental Health component scores. SF-12 will be assessed at Baseline (Day 1) and weeks 24, 48, 96 and/or WD
  • CHANGE FROM BASELINE IN TREATMENT ACCEPTANCE [ Time Frame: Baseline and up to Week 96 ]
    Overall treatment acceptance to chronic therapy will be assessed with 3 items from the ACCEPT questionnaire. It will be assessed at Baseline (Day 1) and weeks 8, 24, 48, 96 and/or WD
  • CHANGE FROM WEEK 4B IN TOLERABILITY OF INJECTION [ Time Frame: Week 4b to Week 96 ]
    Subject reported injection tolerability will be assessed in subjects receiving CAB LA + RPV LA using a single item 11-point Likert-based numeric rating scale (NRS) administered 30-60 minutes following the injections. NRS will be assessed at weeks 4b, 5, 40, 41, and 96

Enrollment: 618
Study Start Date: October 28, 2016
Estimated Study Completion Date: February 8, 2022
Estimated Primary Completion Date: May 29, 2018 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: CAB LA + RPV LA every 4 weeks
Eligible subjects receive Oral CAB 30 mg + RPV 25 mg once daily for four weeks, IM CAB LA 600 mg and RPV LA 900 mg for the first injection, and Week 4 onwards subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks until withdrawal.
Drug: Cabotegravir (CAB) tablet

It is a white oval shaped film coated 30 mg tablets for oral administration. CAB Tablet is composed of cabotegravir sodium, lactose monohydrate, microcrystalline cellulose, hypromellose, sodium starch glycolate, magnesium stearate, and white film-coat

Drug: Rilpivirine (RPV) tablet

It is a 25 mg tablet with off-white, round, biconvex, film-coated and debossed on one side with "TMC" and the other side with "25". Each tablet contains RPV hydrochloride, and the inactive ingredients croscarmellose sodium, lactose monohydrate, magnesium stearate, polysorbate 20, povidone K30 and silicified microcrystalline cellulose

Drug: Cabotegravir - Injectable Suspension (CAB LA)

It is a sterile white to slightly pink suspension containing 200 mg/mL of CAB as free acid for administration by intramuscular (IM) injection. Each vial is for single-dose use containing a withdrawable volume of 2.0 mL, and does not require dilution prior to administration. CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 3350, mannitol, and water for injection

Drug: Rilpivirine - Injectable Suspension (RPV LA)

It is a sterile white suspension containing 300 mg/mL of RPV as the free base. The route of administration is by intramuscular (IM) injection. Each vial contains a nominal fill of 2.0 mL, and does not require dilution prior to administration. RPV LA requires refrigeration and must be protected from light. RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for injection.

Active Comparator: Current antiretroviral regimen
Eligible subjects will continue their current anti-retroviral regimen (2 NRTIs plus an INI, NNRTI, or a PI) for 52 weeks. After 52 weeks subjects have the option to continue study participation by switching to CAB LA + RPV LA in the Extension Phase where they will follow the procedure of CAB LA + RPV LA arm.
Drug: 2 NRTIs plus an INI, NNRTI, or PI
    Acceptable stable (initial or second) ARV regimens include 2 NRTIs plus:
    • INI with the exception of ABC/DTG/3TC (either the initial or second cART regimen)
    • NNRTI (either the initial or second cART regimen)
    • Boosted PI (or atazanavir [ATV] unboosted) (either the initial or second PI-based cART regimen)

    Eligibility

    Eligibility

    Ages Eligible for Study: 18 Years and older  
    Sexes Eligible for Study: All  
    Accepts Healthy Volunteers: No  

    Criteria

    Inclusion Criteria:

    • Aged 18 years or older (or ≥19 where required by local regulatory agencies), at the time of signing the informed consent.
    • Must be on uninterrupted current regimen (either the initial or second ARV regimen) for at least 6 months prior to Screening. Any prior switch, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must NOT have been done for treatment failure (HIV-1 RNA ≥400 c/mL).
    • Acceptable stable (initial or second) ARV regimens prior to Screening include 2 NRTIs plus: INI with the exception of ABC/DTG/3TC (either the initial or second cART regimen);NNRTI (either the initial or second cART regimen);Boosted PI (or atazanavir [ATV] unboosted) (must be either the initial cART regimen or one historical within class switch is permitted due to safety/tolerability) The addition, removal, or switch of a drug(s) that has been used to treat HIV based on antiretroviral properties of the drug constitutes a change in ART with the following limited exceptions: Historical changes in formulations of ART drugs or booster drugs will not constitute a change in ART regimen if the data support similar exposures and efficacy, and the change must have been at least 3 months prior to Screening; Historical perinatal use of an NRTI when given in addition to an ongoing HAART will not be considered a change in ART regimen; A change in dosing scheme of the same drug from twice daily to once daily will not be considered a change in ART regimen if data support similar exposures and efficacy.
    • Documented evidence of at least two plasma HIV-1 RNA measurements <50 c/mL in the 12 months prior to Screening: one within the 6 to 12 month window, and one within 6 months prior to Screening;
    • Plasma HIV-1 RNA <50 c/mL at Screening;
    • A female subjects is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at screen and a negative urine hCG test at Randomization), not lactating, and at least one of the following conditions applies:
      1. Non-reproductive potential defined as: Pre-menopausal females with one of the following: Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up; confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
      2. Reproductive potential and agrees to the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication, and until from 30 days prior to the first dose of study medication throughout the study, and for at least 30 days after discontinuation of all oral study medications and for at least 52 weeks after discontinuation of CAB LA and RPV LA. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.
    • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form. Eligible subjects or their legal guardians (and next of kin when locally required), must sign a written Informed Consent Form before any protocol-specified assessments are conducted. Enrolment of subjects who are unable to provide direct informed consent is optional and will be based on local legal/regulatory requirements and site feasibility to conduct protocol procedures.
    • Subjects enrolled in France must be affiliated to, or a beneficiary of, a social security category.
    • All subjects participating in the study should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of HIV transmission to an uninfected partner.


    Exclusion Criteria:
    • Within 6 months prior to Screening and after confirmed suppression to <50 c/mL on current ART regimen, any plasma HIV-1 RNA measurement ≥50 c/mL
    • Within the 6 to 12 month window prior to Screening and after confirmed suppression to <50 c/mL, any plasma HIV-1 RNA measurement >200 c/mL, or 2 or more plasma HIV-1 RNA measurements ≥50 c/mL
    • Any drug holiday during the window between initiating first HIV ART and 6 months prior to Screening, except for brief periods (less than 1 month) where all ART was stopped due to tolerability and/or safety concerns
    • Any switch to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV-1 RNA measurement ≥400 c/mL after initial suppression to <50 c/mL while on first line HIV therapy regimen)
    • Abacavir/dolutegravir/lamivudine, (ABC/DTG/3TC) as current ART regimen
    • A history of use of any regimen consisting of only single NNRTI therapy (even if only for peri-partum treatment), or only single or dual NRTI therapy prior to starting cART
    • Subjects who are currently participating in or anticipate to be selected for any other interventional study
    • Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study
    • Any evidence of an active Center for Disease Control and Prevention (CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapy and historical or current CD4 cell counts less than 200 cells/mm^3
    • Subjects with moderate to severe hepatic impairment
    • Any pre-existing physical or mental condition (including substance use disorder) which, in the opinion of the Investigator, may interfere with the subjects ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject.
    • Subjects determined by the Investigator to have a high risk of seizures, including subjects with an unstable or poorly controlled seizure disorder. A subject with a prior history of seizure may be considered for enrolment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrolment
    • All subjects will be screened for syphilis (rapid plasma reagin [RPR]). Subjects with untreated syphilis infection, defined as a positive RPR without clear documentation of treatment, are excluded. Subjects with a serofast RPR result (persistence of a reactive nontreponemal syphilis test) despite history of adequate therapy and no evidence of re-exposure may enrol after consultation with the Medical Monitor. Subjects with a positive RPR test who have not been treated may be rescreened at least 30 days after completion of antibiotic treatment for syphilis
    • Subjects who, in the investigator's judgment, pose a significant suicide risk. Subject's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk
    • The subject has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions
    • Evidence of Hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (anti-HBc), Hepatitis B surface antibody (anti-HBs) and HBV DNA as follows:•Subjects positive for HBsAg are excluded;
    • Subjects negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded
    • Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded, however Investigators must carefully assess if therapy specific for HCV infection is required; subjects who are anticipated to require HCV treatment within 12 months must be excluded. (HCV treatment on study may be permitted post Week 48, following consultation with the medical monitor) Subjects with HCV co-infection will be allowed entry into phase 3 studies if: Liver enzymes meet entry criteria; HCV Disease has undergone appropriate work-up, and is not advanced, and will not require treatment prior to the Week 48 visit. Additional information (where available) on subjects with HCV co-infection at screening should include results from any liver biopsy, Fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment. In the event that recent biopsy or imaging data is not available or inconclusive, the Fib-4 score will be used to verify eligibility: Fib-4 score > 3.25 is exclusionary; Fib-4 scores 1.45 - 3.25 requires Medical Monitor consultation Fibrosis 4 Score Formula:( Age x AST ) / ( Platelets x ( sqr [ ALT ])
    • Unstable liver disease (as defined by any of the following: presence of ascites,encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices,or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment)
    • History of liver cirrhosis with or without hepatitis viral co-infection.
    • Ongoing or clinically relevant pancreatitis
    • Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease
    • Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the subject prior to randomization
    • Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the subject unable to receive study medication
    • History or presence of allergy or intolerance to the study drugs or their components or drugs of their class. In addition, if heparin is used during PK sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia must not be enrolled
    • Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid (≤325mg).
    • Any evidence of primary resistance based on the presence of any major known INI or NNRTI resistance-associated mutation, except for K103N, (International AIDS Society [IAS]-USA, 2015) by any historical resistance test result.
    • Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening phase to verify a result
    • Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the subject's participation in the study of an investigational compound
    • Subject has estimated creatine clearance <50mL/min per 1.73m^2 via CKDEPI Method
    • Alanine aminotransferase (ALT) ≥3 × ULN Exposure to an experimental drug or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to Day 1 of this study;
    • Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid,INH); anti-coagulation agents; Immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons. Note: Subjects using short term (e.g. ≤21 days) systemic corticosteroid treatment; topical, inhaled and intranasal corticosteroids are eligible for enrolment.
    • Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
    • Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 within 28 days of study Day 1
    • Use of medications which are associated with Torsade de Pointes.
    • Current or prior history of etravirine (ETR)
    • Current use of tipranavir/ritonavir or fosamprenavir/ritonavir
    • Subjects receiving any prohibited medication and who are unwilling or unable to switch
    to an alternate medication.

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT02951052

    Locations

    United States, Alabama
    GSK Investigational Site
    Birmingham, Alabama, United States, 35294
    United States, Arizona
    GSK Investigational Site
    Phoenix, Arizona, United States, 85015
    United States, California
    GSK Investigational Site
    Bakersfield, California, United States, 93301
    GSK Investigational Site
    Beverly Hills, California, United States, 90211
    GSK Investigational Site
    Long Beach, California, United States, 90813
    GSK Investigational Site
    Los Angeles, California, United States, 90036
    GSK Investigational Site
    Los Angeles, California, United States, 90069
    GSK Investigational Site
    Palm Springs, California, United States, 92264
    GSK Investigational Site
    San Francisco, California, United States, 94109
    GSK Investigational Site
    San Francisco, California, United States, 94110
    United States, Colorado
    GSK Investigational Site
    Denver, Colorado, United States, 80209
    United States, District of Columbia
    GSK Investigational Site
    Washington, District of Columbia, United States, 20007
    GSK Investigational Site
    Washington, District of Columbia, United States, 20009
    GSK Investigational Site
    Washington, District of Columbia, United States, 20037
    United States, Florida
    GSK Investigational Site
    Fort Lauderdale, Florida, United States, 33316
    GSK Investigational Site
    Fort Pierce, Florida, United States, 34982
    GSK Investigational Site
    Sarasota, Florida, United States, 34237
    GSK Investigational Site
    Vero Beach, Florida, United States, 32960-6571
    United States, Georgia
    GSK Investigational Site
    Macon, Georgia, United States, 31201
    United States, Illinois
    GSK Investigational Site
    Chicago, Illinois, United States, 60611
    United States, Massachusetts
    GSK Investigational Site
    Boston, Massachusetts, United States, 02129
    United States, Michigan
    GSK Investigational Site
    Detroit, Michigan, United States, 48202
    United States, Missouri
    GSK Investigational Site
    Saint Louis, Missouri, United States, 63110
    United States, Nebraska
    GSK Investigational Site
    Omaha, Nebraska, United States, 68198
    United States, New York
    GSK Investigational Site
    Buffalo, New York, United States, 14201
    GSK Investigational Site
    New York, New York, United States, 10016
    GSK Investigational Site
    New York, New York, United States, 10029
    United States, North Carolina
    GSK Investigational Site
    Chapel Hill, North Carolina, United States, 27599-7064
    GSK Investigational Site
    Charlotte, North Carolina, United States, 28209
    United States, Ohio
    GSK Investigational Site
    Cincinnati, Ohio, United States, 45267-0405
    United States, Pennsylvania
    GSK Investigational Site
    Allentown, Pennsylvania, United States, 18102
    GSK Investigational Site
    Pittsburgh, Pennsylvania, United States, 15212
    United States, Texas
    GSK Investigational Site
    Austin, Texas, United States, 78705
    GSK Investigational Site
    Dallas, Texas, United States, 75246
    GSK Investigational Site
    Houston, Texas, United States, 77098
    United States, Virginia
    GSK Investigational Site
    Annandale, Virginia, United States, 22003
    GSK Investigational Site
    Lynchburg, Virginia, United States, 24501
    Argentina
    GSK Investigational Site
    Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, C1405CKC
    GSK Investigational Site
    Ciudad de Buenos Aires, Buenos Aires, Argentina, C1202ABB
    GSK Investigational Site
    Rosario, Santa Fe, Argentina, 2000
    GSK Investigational Site
    Buenos Aires, Argentina, 1141
    Australia
    GSK Investigational Site
    Darlinghurst, Sydney, New South Wales, Australia, 2010
    GSK Investigational Site
    Darlinghurst, New South Wales, Australia, 2010
    GSK Investigational Site
    Sydney, New South Wales, Australia, 2010
    GSK Investigational Site
    Prahran, Victoria, Australia, 3181
    Canada
    GSK Investigational Site
    Vancouver, British Columbia, Canada, V6Z 2T1
    GSK Investigational Site
    Ottawa, Ontario, Canada, K1H 8L6
    GSK Investigational Site
    Toronto, Ontario, Canada, M4T 3A7
    GSK Investigational Site
    Toronto, Ontario, Canada, M5G 1K2
    GSK Investigational Site
    Montreal, Quebec, Canada, H2L 4E9
    GSK Investigational Site
    Montreal, Quebec, Canada, H4A 3J1
    GSK Investigational Site
    Regina, Saskatchewan, Canada, S4P 0W5
    GSK Investigational Site
    Québec, Canada, G1V 4G2
    France
    GSK Investigational Site
    Montpellier Cedex 5, France, 34295
    GSK Investigational Site
    Paris Cedex 10, France, 75475
    GSK Investigational Site
    Paris Cedex 12, France, 75571
    GSK Investigational Site
    Paris Cedex 13, France, 75651
    GSK Investigational Site
    Paris, France, 75018
    GSK Investigational Site
    Saint Denis Cedex 01, France, 93205
    GSK Investigational Site
    Toulouse cedex 9, France, 31059
    GSK Investigational Site
    Tourcoing cedex, France, 59208
    Germany
    GSK Investigational Site
    Muenchen, Bayern, Germany, 80335
    GSK Investigational Site
    Frankfurt am Main, Hessen, Germany, 60590
    GSK Investigational Site
    Frankfurt, Hessen, Germany, 60596
    GSK Investigational Site
    Hannover, Niedersachsen, Germany, 30625
    GSK Investigational Site
    Bonn, Nordrhein-Westfalen, Germany, 53127
    GSK Investigational Site
    Essen, Nordrhein-Westfalen, Germany, 45122
    GSK Investigational Site
    Berlin, Germany, 10439
    GSK Investigational Site
    Berlin, Germany, 12157
    GSK Investigational Site
    Hamburg, Germany, 20146
    GSK Investigational Site
    Hamburg, Germany, 20246
    Italy
    GSK Investigational Site
    Brescia, Lombardia, Italy, 25123
    GSK Investigational Site
    Milano, Lombardia, Italy, 20157
    Korea, Republic of
    GSK Investigational Site
    Busan, Korea, Republic of, 49241
    GSK Investigational Site
    Daegu, Korea, Republic of, 41944
    GSK Investigational Site
    Daejeon, Korea, Republic of, 35015
    GSK Investigational Site
    Seoul, Korea, Republic of, 03722
    GSK Investigational Site
    Seoul, Korea, Republic of, 06591
    Mexico
    GSK Investigational Site
    Guadalajara, Jalisco, Mexico, 44280
    Russian Federation
    GSK Investigational Site
    Ekaterinburg, Russian Federation, 620149
    GSK Investigational Site
    Kazan, Russian Federation, 420061
    GSK Investigational Site
    Kemerovo, Russian Federation, 650056
    GSK Investigational Site
    Krasnodar, Russian Federation, 350015
    GSK Investigational Site
    Lipetsk, Russian Federation, 398043
    GSK Investigational Site
    Moscow, Russian Federation, 105275
    GSK Investigational Site
    Orel, Russian Federation, 302040
    GSK Investigational Site
    Saratov, Russian Federation, 410009
    GSK Investigational Site
    Smolensk, Russian Federation, 214006
    GSK Investigational Site
    St. Petersburg, Russian Federation, 190103
    GSK Investigational Site
    St. Petersburg, Russian Federation, 193167
    GSK Investigational Site
    St. Petersburg, Russian Federation, 196645
    GSK Investigational Site
    Toliyatti, Russian Federation, 445846
    South Africa
    GSK Investigational Site
    Bloemfontein, Free State, South Africa, 9301
    GSK Investigational Site
    Brandfort, Free State, South Africa, 9400
    GSK Investigational Site
    Johannesburg, Gauteng, South Africa, 2092
    GSK Investigational Site
    Johannesburg, Gauteng, South Africa, 2113
    GSK Investigational Site
    Pretoria, Gauteng, South Africa, 0087
    GSK Investigational Site
    Durban, KwaZulu- Natal, South Africa, 4001
    GSK Investigational Site
    Wentworth, KwaZulu- Natal, South Africa, 4052
    GSK Investigational Site
    Middelburg, Mpumalanga, South Africa, 1055
    GSK Investigational Site
    Durban, South Africa, 4001
    GSK Investigational Site
    Observatory, Cape Town, South Africa, 7925
    Spain
    GSK Investigational Site
    Badalona, Spain, 08916
    GSK Investigational Site
    Barcelona, Spain, 08003
    GSK Investigational Site
    Barcelona, Spain, 08035
    GSK Investigational Site
    Barcelona, Spain, 08036
    GSK Investigational Site
    Córdoba, Spain, 14004
    GSK Investigational Site
    Elche (Alicante), Spain, 03203
    GSK Investigational Site
    Madrid, Spain, 28034
    GSK Investigational Site
    Madrid, Spain, 28041
    GSK Investigational Site
    Madrid, Spain, 28046
    GSK Investigational Site
    Malaga, Spain, 29010
    GSK Investigational Site
    Santiago de Compostela, Spain, 15706
    GSK Investigational Site
    Sevilla, Spain, 41013
    GSK Investigational Site
    Valencia, Spain, 46014
    GSK Investigational Site
    Vigo, Spain, 36312
    Sweden
    GSK Investigational Site
    Göteborg, Sweden, SE-416 85
    GSK Investigational Site
    Stockholm, Sweden, SE-118 83
    GSK Investigational Site
    Stockholm, Sweden, SE-14186

    Sponsors and Collaborators

    ViiV Healthcare
    Janssen Pharmaceuticals
    GlaxoSmithKline

    Investigators

    Study Director: GSK Clinical Trials ViiV Healthcare
    More Information

    More Information


    Responsible Party: ViiV Healthcare  
    ClinicalTrials.gov Identifier: NCT02951052   History of Changes  
    Other Study ID Numbers: 201585  
    Study First Received: September 15, 2016  
    Last Updated: September 10, 2018  
    Individual Participant Data    
    Plan to Share IPD: Yes  

    Studies a U.S. FDA-regulated Device Product: No  

    Keywords provided by ViiV Healthcare:

    Long-acting cabotegravir
    Virologic failure
    long-acting rilpivirine
    Antiretroviral

    Additional relevant MeSH terms:
    Immunologic Deficiency Syndromes
    Acquired Immunodeficiency Syndrome
    HIV Infections
    Rilpivirine

    ClinicalTrials.gov processed this data on September 20, 2018
    This information is provided by ClinicalTrials.gov.