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Clinical Trials

MainTitle

Efficacy, Safety and Tolerability Study of Long-acting Cabotegravir Plus Long-acting Rilpivirine (CAB LA + RPV LA) in Human-immunodeficiency Virus-1 (HIV-1) Infected Adults

This study is not yet open for participant recruitment. (see Contacts and Locations)

Verified October 2017 by ViiV Healthcare

Sponsor
ViiV Healthcare

Collaborator
Janssen Research and Development

Information provided by (Responsible Party)
ViiV Healthcare
ClinicalTrials.gov Identifier
NCT03299049

First received: September 26, 2017
Last updated: October 3, 2017
Last Verified: October 2017
History of Changes
Purpose

Purpose

This Antiretroviral Therapy as Long Acting Suppression every 2 Months (ATLAS-2M) study is designed to demonstrate the non-inferior antiviral activity and safety of CAB LA + RPV LA administered every 8 weeks (Q8W) compared to CAB LA + RPV LA administered every 4 weeks (Q4W) over a 48-week treatment period in approximately 1020 adult HIV-1 infected subjects. Subjects will be divided in 2 groups; Group 1 will include subjects receiving current anti-retroviral (ART) standard of care (SOC) therapy whereas group 2 will include subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in both groups will be randomized to receive CAB LA + RPV LA Q4W or Q8W. The study will be carried out in 3 phases including screening phase, maintenance phase and extension phase. Subjects choosing not to enter the Extension phase can complete their study participation at the Week 100 visit and enter into the 52-week Long-Term Follow-Up (LTFU) Phase as required.

Condition Intervention Phase
Infection, Human Immunodeficiency Virus

Drug : Cabotegravir Tablets
Drug : Rilpivirine Tablets
Drug : Cabotegravir Injectable Suspension
Drug : Rilpivirine Injectable Suspension
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Two groups of subjects will be randomized to receive CAB LA + RPV LA Q4W, or CAB LA + RPV LA Q8W regimen
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIIb, Randomized, Multicenter, Parallel-group, Non-inferiority, Open-label Study Evaluating the Efficacy, Safety, and Tolerability of Long-acting Cabotegravir Plus Long-acting Rilpivirine Administered Every 8 Weeks or Every 4 Weeks in HIV-1-infected Adults Who Are Virologically Suppressed

Further study details as provided by ViiV Healthcare:

Primary Outcome Measures

  • Percentage of subjects with plasma HIV ribonucleic acid (RNA) >=50 copies per milliliter (copies/mL) at Week 48 [ Time Frame: Week 48 ]
    Virologic outcome for each subject will be calculated according to the food and drug administration's (FDA) Snapshot algorithm. As defined by the Snapshot algorithm, HIV-RNA >=50 copies/mL is determined by the last available HIV-1 RNA measurement while the subject is on treatment within the analysis visit window of interest.
Secondary Outcome Measures:
  • Percentage of subjects with plasma HIV-1 RNA <50 copies/mL at Week 48 and Week 96 [ Time Frame: Week 48 and Week 96 ]
    The antiviral and immunologic activity of CAB LA + RPV LA Q8W will be compared to CAB LA + RPV LA Q4W at Week 48 and Week 96 using the FDA Snapshot algorithm. Subjects with last available HIV-1 RNA measurement <50 copies/mL while the subject is on treatment within the analysis visit window of interest are classified as responders; subjects without evaluable HIV-RNA data for the visit of interest or who change treatment not permitted per protocol before the analysis window are considered non-responders.
  • Percentage of subjects with protocol-defined confirmed virologic failure (CVF) [ Time Frame: Up to Week 96 ]
    CVF is defined as rebound as indicated by two consecutive plasma HIV-1 RNA levels >=200 copies/mL after prior suppression to <200 copies/mL. CVF will be analyzed through Week 48 and Week 96 as a measure of antiviral and immunologic activity of CAB LA and RPV LA.
  • Percentage of subjects with HIV-RNA >=50 copies/mL at Week 96 [ Time Frame: Week 96 ]
    Virologic outcome for each subject will be calculated according to the FDA Snapshot algorithm. As defined by the Snapshot algorithm, HIV-RNA >=50 copies/mL is determined by the last available HIV-1 RNA measurement while the subject is on treatment within the analysis visit window of interest.
  • Change from Baseline in viral load [ Time Frame: Baseline, Week 48 and Up to Week 96 ]
    Change from Baseline in viral load will be assessed over time including Week 48 and Week 96.
  • Change from Baseline in cluster of differentiation (CD)4+ cell counts [ Time Frame: Baseline, Week 48 and Up to Week 96 ]
    Lymphocyte subsets will be collected for assessment by flow cytometry at specific time points including Week 48 and Week 96.
  • Number of subjects with Adverse events (AEs) and serious AEs [ Time Frame: Up to 52 weeks after last dose of study treatment ]
    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 clinical chemistry values [ Time Frame: Up to 52 weeks after last dose of study treatment ]
    Clinical chemistry parameters including blood urea nitrogen (BUN), creatinine, glucose, sodium, potassium, chloride, total carbon-di-oxide (CO2), lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, phosphate, total bilirubin, albumin, creatine phosphokinase and lipid panel will be analyzed as a measure of safety.
  • Number of subjects with abnormal clinical hematology values [ Time Frame: Up to 52 weeks after last dose of study treatment ]
    Clinical hematology parameters including platelet count, red blood cell (RBC) count, white blood cell (WBC) count, hemoglobin, hematocrit, mean corpuscle volume (MCV), neutrophils, lymphocytes, monocytes, eosinophils and basophils will be analyzed as a measure of safety.
  • Percentage of subjects who discontinue treatment due to AEs [ Time Frame: Up to 52 weeks after last dose of study treatment ]
    Subjects who discontinue treatment due to AEs will be analyzed as a measure of safety.
  • Change from Baseline in albumin [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in albumin will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in Alkaline phosphatase, ALT, AST, creatine phosphokinase, lipase [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in Alkaline phosphatase, ALT, AST, creatine phosphokinase, lipase will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in total bilirubin and creatinine [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in total bilirubin and creatinine will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in glucose, sodium, potassium, total CO2, BUN, chloride, phosphate [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in glucose, sodium, potassium, total CO2, BUN, chloride, phosphate will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in total cholesterol, High density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol and triglycerides [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in creatinine clearance [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in creatinine clearance will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in basophils, eosinophils, monocytes, lymphocytes, neutrophils and platelet count [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in basophils, eosinophils, monocytes, lymphocytes, neutrophils and platelet count will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in hematocrit levels [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in hematocrit levels will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in hemoglobin levels [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in hemoglobin levels will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in RBC count [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in RBC count will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in WBC count [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in WBC count will be assessed up to long-term follow-up visits as a measure of safety.
  • Change from Baseline in MCV levels [ Time Frame: Baseline and Up to 52 weeks after last dose of study treatment ]
    Change from Baseline in MCV levels will be assessed up to long-term follow-up visits as a measure of safety.
  • Number of incidences of treatment emergent genotypic resistance [ Time Frame: Up to Week 96 ]
    Whole venous blood samples will be obtained from each subject for analysis of potential genotypic resistance to CAB, RPV.
  • Number of incidences of treatment emergent phenotypic resistance [ Time Frame: Up to Week 96 ]
    Whole venous blood samples will be obtained from each subject for analysis of potential phenotypic resistance to CAB, RPV.
  • Trough plasma concentration (Ctrough) of CAB LA: Q4W dosing [ Time Frame: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
  • Ctrough of RPV LA: Q4W dosing [ Time Frame: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
  • Ctrough of CAB LA: Q8W dosing [ Time Frame: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
  • Ctrough of RPV LA: Q8W dosing [ Time Frame: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
  • Maximum plasma concentration (Cmax) of CAB LA: Q4W dosing [ Time Frame: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
  • Cmax of RPV LA: Q4W dosing [ Time Frame: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
  • Cmax of CAB LA: Q8W dosing [ Time Frame: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
  • Cmax of RPV LA: Q8W dosing [ Time Frame: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
  • Area under the curve (AUC) of CAB LA: Q4W dosing [ Time Frame: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
  • AUC of RPV LA: Q4W dosing [ Time Frame: Pre-dose at Week 4B, 8, 16, 24, 32, 40, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
  • AUC of CAB LA: Q8W dosing [ Time Frame: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of CAB LA.
  • AUC of RPV LA: Q8W dosing [ Time Frame: Pre-dose at Week 8, 9, 16, 24, 32, 40, 41, 48 and 96 ]
    Blood samples will be collected at specific time points for pharmacokinetic analysis of RPV LA.
  • Number of subjects with different demographic parameters: For inter-participant 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 participant variability for pharmacokinetic parameters.
  • Number of subjects with different demographic parameters: For intra participant 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 participant variability for pharmacokinetic parameters.
  • Change from Baseline in health related quality of life (HRQoL) of subjects using the HIV/Acquired immunodeficiency syndrome (AIDS) Targeted Quality of Life (HAT-QoL) questionnaire [ Time Frame: Baseline, Week 24 and Week 48 ]
    The HAT-QoL is a 42-item questionnaire grouped into nine dimensions, assessing overall function and well-being. A shorter version of this original HAT-QoL will be used in the present study which will contain 14-items grouped into the three following dimensions: "life satisfaction", "disclosure worries" and "HIV medication". All items use a ''past 4 weeks'' timeframe and a Likert response scale from 1=''all of the time'' to 5=''none of the time''.
  • Change from Baseline in total "treatment satisfaction" score of the HIV Treatment Satisfaction Status Questionnaire (HIVTSQs) [ Time Frame: Baseline, Week 24 and Week 48 ]
    HIVTSQ is a 10-item questionnaire which is used specifically to measure satisfaction with medication for people infected with HIV.
  • Change from Baseline in individual item score of HIVTSQs [ Time Frame: Baseline and Up to Week 48 ]
    HIVTSQ is a 10-item questionnaire which is used specifically to measure satisfaction with medication for people infected with HIV.
  • Change in treatment satisfaction using the HIV Treatment Satisfaction Change Questionnaire (HIVTSQc) [ Time Frame: Week 48 ]
    HIVTSQc is the change version of original HIVTSQs. HIVTSQc enhances the sensitivity by allowing those who were satisfied at Baseline to express even greater satisfaction at follow-up.
  • Change from Week 8 in Dimension scores using the Perception of iNjection questionnaire (PIN) [ Time Frame: Week 8, 24 and 48 ]
    Change from Week 8 in dimension score which assess Bother of Injection Site Reactions (ISRs), Leg movement, Sleep, and Injection Acceptance will be evaluated using PIN questionnaire. This measure contains 21 items and scores range from 1 to 5 where 1= the most favorable perception of vaccination while 5= the most unfavorable.
  • Change from Week 8 in individual item score using PIN [ Time Frame: Week 8 and Up to Week 48 ]
    Change from Week 8 in individual item scores which 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 will be evaluated using the PIN questionnaire. This measure contains 21 items and scores range from 1 to 5 where 1= the most favorable perception of vaccination while 5= the most unfavorable.
  • Change from Baseline in treatment acceptance using the "General acceptance" dimension of the Chronic Treatment Acceptance (ACCEPT) questionnaire [ Time Frame: Baseline, Week 24 and Week 48 ]
    The ACCEPT questionnaire, a 25 item questionnaire, is a generic medication acceptance measure assessing how patients weigh advantages and disadvantages of long-term medications. The study will use three questions that focus on general acceptance of study medication.
  • CD4+ cell counts [ Time Frame: Baseline, Week 48 and Up to Week 96 ]
    Lymphocyte subsets will be collected for assessment by flow cytometry at specific time points including Week 48 and Week 96.

Estimated Enrollment: 1020
Anticipated Study Start Date: October 26, 2017
Estimated Study Completion Date: March 7, 2022
Estimated Primary Completion Date: May 31, 2019 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Subjects in group 1 receiving study treatment once in 4 weeks
Group 1 will consist of subjects randomized from current ART SOC therapy. Subjects in group 1 will be randomized to receive CAB LA plus RPV LA Q4W via intramuscular (IM) route. All subjects will receive oral therapy with CAB 30 mg + RPV 25 mg once daily prior to randomization.
Drug: Cabotegravir Tablets

CAB tablets are white to almost white oval shaped film coated 30 mg tablets for oral administration. CAB tablets are to be stored up to 30 degree Celsius and protected from moisture.

Drug: Rilpivirine Tablets

RPV tablets are 25 mg tablets that are off-white, round, biconvex, film-coated and debossed on one side with "TMC" and the other side with "25". RPV tablets should be stored at 25 degree Celsius (excursions permitted to 15 degree-30 degree Celsius) and protected from light.

Drug: Cabotegravir Injectable Suspension

CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 mg/mL of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be freezed.

Drug: Rilpivirine Injectable Suspension

RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be freezed. RPV LA should also be protected from light.

Experimental: Subjects in group 1 receiving study treatment once in 8 weeks
Group 1 will consist of subjects randomized from current ART SOC therapy. Subjects in group 1 will be randomized to receive CAB LA plus RPV LA Q8W via IM route. All subjects will receive oral therapy with CAB 30 mg + RPV 25 mg once daily prior to randomization.
Drug: Cabotegravir Tablets

CAB tablets are white to almost white oval shaped film coated 30 mg tablets for oral administration. CAB tablets are to be stored up to 30 degree Celsius and protected from moisture.

Drug: Rilpivirine Tablets

RPV tablets are 25 mg tablets that are off-white, round, biconvex, film-coated and debossed on one side with "TMC" and the other side with "25". RPV tablets should be stored at 25 degree Celsius (excursions permitted to 15 degree-30 degree Celsius) and protected from light.

Drug: Cabotegravir Injectable Suspension

CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 mg/mL of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be freezed.

Drug: Rilpivirine Injectable Suspension

RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be freezed. RPV LA should also be protected from light.

Experimental: Subjects in group 2 receiving study treatment once in 4 weeks
Group 2 will consist of subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in Group 2 will be randomized to continue CAB LA plus RPV LA Q4W administration via IM route.
Drug: Cabotegravir Injectable Suspension

CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 mg/mL of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be freezed.

Drug: Rilpivirine Injectable Suspension

RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be freezed. RPV LA should also be protected from light.

Experimental: Subjects in group 2 receiving study treatment once in 8 weeks
Group 2 will consist of subjects currently receiving CAB LA + RPV LA Q4W in ATLAS study. Subjects in Group 2 will be randomized to receive CAB LA plus RPV LA Q8W via IM route.
Drug: Cabotegravir Injectable Suspension

CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 mg/mL of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be freezed.

Drug: Rilpivirine Injectable Suspension

RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be freezed. RPV LA should also be protected from light.

Eligibility

Eligibility

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

Criteria

Inclusion Criteria:

  • Subjects who will be able to understand and comply with protocol requirements, instructions, and restrictions.
  • Understand the long term commitment to the study and be likely to complete the study as planned
  • Be considered as an appropriate candidate for participation in an investigative clinical trial with oral and intramuscularly injectable medications (e.g., no active substance use disorder, acute major organ disease, or planned long-term work assignments out of the country, etc.).
  • Aged 18 years or older (or >=19 where required by local regulatory agencies), at the time of signing the informed consent.
  • A female is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin (hCG) test at screen and a negative urine hCG test at Randomization), not lactating, and at least one of the following conditions applies:

  • 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 (refer to laboratory reference ranges for confirmatory levels)]. 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 enrollment.
    Reproductive potential and agrees to follow one of 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, throughout the study, 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 participants understand how to properly use these methods of contraception.
  • Capable of giving signed informed consent. 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. Enrollment 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.
  • Subjects receiving oral SOC treatment for HIV-1 (not participating in ATLAS Trial) must be on uninterrupted current regimen [either the initial or second anti-retroviral (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 copies/mL).
  • For subjects receiving oral SOC treatment for HIV-1 (not participating in ATLAS Trial) Documented evidence of at least two plasma HIV-1 RNA measurements <50 copies/mL in the 12 months prior to Screening: one within the 6 to 12-month window, and one within 6 months prior to Screening.
  • For subjects receiving oral SOC treatment for HIV-1 (not participating in ATLAS Trial): Plasma HIV-1 RNA <50 copies/mL at Screening
  • Subjects transitioning from 201585 (ATLAS) must have been on CAB LA 400 milligram (mg) + RPV LA 600 mg Q4W or "Current ART" regimen through at minimum Week 52 of the ATLAS study as per ATLAS protocol dosing requirements and until Day 1 of the ATLAS-2M study. Any disruptions in dosing during ATLAS must be discussed with the Medical Monitor for a final determination of eligibility.
  • For Participants transitioning from 201585 (ATLAS): plasma HIV-1 RNA <50 copies/mL at Screening


Exclusion Criteria:

    For subjects not transitioning from 201585 (ATLAS):
  • Within 6 months prior to Screening, any plasma HIV-1 RNA measurement >=50 copies/mL
  • Within the 6 to 12-month window prior to Screening, any plasma HIV-1 RNA measurement >200 copies/mL, or 2 or more plasma HIV-1 RNA measurements >=50 copies/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 >=200 copies/mL after initial suppression to <50 copies/mL while on first line HIV therapy regimen)
  • A history of use of any regimen consisting of only mono or dual HIV-1 therapy (even if only for peri-partum treatment). Subjects who are currently participating in or anticipate to be selected for any other interventional study with the exception of the 201585 (ATLAS) study.

  • For Subjects transitioning from 201585 (ATLAS):
  • During participation in ATLAS, consecutive (2 or more sequential) plasma HIV-1 RNA measurements >=50 copies/mL
  • During participation in ATLAS, any HIV-1 RNA measurement >=200 copies/mL
  • More than two total measurements of plasma HIV-1 RNA >=50 c/mL during participation in the ATLAS trial will require direct approval by the ATLAS-2M Medical Monitor and Study virologist for study participation.

  • For all subjects:
  • Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.
  • Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3 disease except cutaneous Kaposi's sarcoma not requiring systemic therapy.
  • 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 subject's 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 participants with an unstable or poorly controlled seizure disorder. A subject with a prior history of seizure may be considered for enrollment 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 enrollment.
  • All subjects will be screened for syphilis (rapid plasma reagin [RPR]). Subjects with untreated secondary (late latent) or tertiary syphilis infection, defined as a positive RPR and a positive treponemal test without clear documentation of treatment, are excluded. Subjects with a false positive RPR (with negative treponemal test) or serofast RPR result (persistence of a reactive nontreponemal syphilis test despite history of adequate therapy and no evidence of re-exposure) may enroll after consultation with the Medical Monitor. Participants with primary syphilis or early latent secondary syphilis (acquired within the preceding year) who have a positive RPR test and have not been treated may be treated during the screening period and if completion of antibiotic treatment occurs during the screening period, may be allowed entry after consultation with the Medical Monitor. If antibiotic treatment cannot be completed before the screening window ends, subjects may be rescreened once following completion of antibiotic therapy for primary or early latent secondary 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 deoxyribonucleic acid (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. Note: Participants positive for anti-HBc (negative HBsAg status) and positive for anti-HBs (past and/or current evidence) are immune to HBV and are not 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; participants who are anticipated to require HCV treatment within 12 months must be excluded. (HCV treatment on study may be permitted post Week 52, following consultation with the medical monitor).
  • Subjects with HCV co-infection will be allowed entry into this study 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 52 visit. Additional information (where available) on participants 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 ( square [ 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 participant 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 participant 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 pharmacokinetic sampling, participants 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 (<=325 mg)
  • Any evidence of primary resistance based on the presence of any major known Integrase inhibitor (INI) or Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutation, except for K103N 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.
  • Subjects has estimated creatine clearance <50mL/minute per 1.73 meter square (m^2) via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method
  • Alanine aminotransferase (ALT) >=3 × Upper limit of normal (ULN)
  • Exposure to an experimental drug (with the exception of those in the ATLAS study including CAB, CAB LA, and RPV LA) 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 enrollment.
  • 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. Treatment with acyclovir/valacyclovir is permitted.
  • Use of medications which are associated with Torsade de Pointes.
  • Current or prior history of etravirine (ETR) use.
  • 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: NCT03299049

Contacts

Contact:   US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Sponsors and Collaborators

ViiV Healthcare
Janssen Research and Development

Investigators

Study Director: GSK Clinical Trials ViiV Healthcare
More Information

More Information


Responsible Party: ViiV Healthcare  
ClinicalTrials.gov Identifier: NCT03299049   History of Changes  
Other Study ID Numbers: 207966  
Study First Received: September 26, 2017  
Last Updated: October 3, 2017  

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

Keywords provided by ViiV Healthcare:

Long acting Cabotegravir
Safety
HIV-1
Efficacy
Tolerability
ATLAS-2M
Long acting Rilpivirine

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

ClinicalTrials.gov processed this data on October 20, 2017
This information is provided by ClinicalTrials.gov.