Clinical Trials

MainTitle

The LATITUDE Study: Long-Acting Therapy to Improve Treatment SUccess in Daily LifE

This study is ongoing, but not recruiting participants.
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator
ViiV

Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT03635788

First received: August 15, 2018
Last updated: April 6, 2020
Last Verified: April 2020
History of Changes
Purpose

Purpose

The purpose of this study is to compare the efficacy, safety, and durability of two different strategies to treat participants with a history of sub-optimal adherence and control of their HIV infection: long-acting (LA) antiretroviral therapy (ART) and all-oral standard of care (SOC).

Condition Intervention Phase
HIV Infections

Drug : Standard of Care (SOC) Oral ART
Drug : Oral RPV
Drug : Oral CAB
Drug : RPV-LA Loading Dose
Drug : CAB-LA Loading Dose
Drug : RPV-LA Maintenance Dose
Drug : CAB-LA Maintenance Dose
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 Study to Evaluate Long-Acting Antiretroviral Therapy in Non-Adherent HIV-Infected Individuals

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures

  • Time to regimen failure in Step 2 [ Time Frame: Measured through Step 2, Week 52 ]
    Time will be measured from Step 2 randomization to the first of the following two events: virologic failure or permanent discontinuation of randomized study treatment
Secondary Outcome Measures:
  • Time to virologic failure in Step 2 [ Time Frame: Measured through Step 2, Week 52 ]
    Virologic failure is defined as confirmed HIV-1 RNA greater than 200 copies/mL after Step 2 randomization
  • Time to the treatment-related failure in Step 2 [ Time Frame: Measured through Step 2, Week 52 ]
    Time will be measured from the Step 2 randomization to the first of the following events: virologic failure or treatment discontinuation due to adverse event (AE)
  • Number of participants with virologic success [ Time Frame: Measured through Step 2, Week 48 ]
    Virologic success will be defined by the US Food and Drug Administration (FDA) Snapshot algorithm
  • Number of participants with plasma HIV-1 RNA level less than 50 copies/mL [ Time Frame: Measured through Step 2, Week 52 ]
  • Frequency of AEs [ Time Frame: Measured through Step 2, Week 52 ]
    AEs will be graded based on the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017
  • Time to discontinuation of randomized treatment in Step 2 [ Time Frame: Measured through Step 2, Week 52 ]
    Time will be measured from Step 2 randomization to the permanent discontinuation of randomized study treatment.
  • Summary score of HIV Treatment Satisfaction Questionnaire (HIVTSQ) [ Time Frame: Measured through Step 2, Week 52 ]
  • Pill count in Step 1 [ Time Frame: Measured through Step 1, Week 24 ]
  • Pill count for participants who randomized to SOC arm in Step 2 [ Time Frame: Measured through Step 2, Week 52 ]
  • Frequency of missed or delayed injections for participants who received LA ART in Step 2 [ Time Frame: Measured through Step 2, Week 52 ]
  • Summary scores of HIV Treatment Adherence Self-Efficacy Scale [ Time Frame: Measured through Step 2, Week 52 ]
  • Frequency of new drug-resistance mutations in participants with virologic failure in Step 2 [ Time Frame: Measured through Step 2, Week 52 ]
    Summarized and tabulated by randomized treatments
  • Frequency of Injection Site Reactions (ISR) during Step 2 [ Time Frame: Measured through Step 2, Week 52 ]

Estimated Enrollment: 350
Study Start Date: March 28, 2019
Estimated Study Completion Date: September 26, 2024
Estimated Primary Completion Date: September 1, 2022 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: Arm A: LA ART
In Step 1, participants will receive SOC oral ART regimen for 24 weeks. In Step 2, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks, followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by a RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 44 weeks. In Step 3, participants will receive a RPV-LA maintenance dose and a CAB-LA maintenance dose every 4 weeks for 52 weeks. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART.
Drug: Standard of Care (SOC) Oral ART

SOC oral ART regimen must include at least 3 drugs with 2 or more drugs predicted to be fully active, including a boosted protease inhibitor (PI) and/or an integrase strand transfer inhibitor (INSTI)

Drug: Oral RPV

RPV 25 mg tablets

Other Name: Rilpivirine
Drug: Oral CAB

CAB 30 mg tablets

Other Name:
  • Cabotegravir
  • GSK1265744

Drug: RPV-LA Loading Dose

900 mg administered as one 3 mL (900 mg) intramuscular injection in the gluteal muscle

Other Name: Rilpivirine Long-Acting Injectable
Drug: CAB-LA Loading Dose

600 mg administered as one 3 mL (600 mg) intramuscular injection in the gluteal muscle

Other Name: Cabotegravir Long-Acting Injectable
Drug: RPV-LA Maintenance Dose

600 mg administered as one 2 mL (600 mg) intramuscular injection in the gluteal muscle

Other Name: Rilpivirine Long-Acting Injectable
Drug: CAB-LA Maintenance Dose

400 mg administered as one 2 mL (400 mg) intramuscular injection in the gluteal muscle

Other Name: Cabotegravir Long-Acting Injectable
Active Comparator: Arm B: SOC Oral ART
In Step 1, participants will receive SOC oral ART regimen for 24 weeks. In Step 2, participants will continue SOC oral ART regimen for 52 weeks. In Step 3, participants will receive oral RPV once daily and oral CAB once daily for 4 weeks, followed by a RPV-LA loading dose and a CAB-LA loading dose, followed in 4 weeks by a RPV-LA maintenance dose and CAB-LA maintenance dose every 4 weeks for 44 weeks. In Step 4, eligible participants will be followed until they complete 52 weeks on locally sourced oral ART.
Drug: Standard of Care (SOC) Oral ART

SOC oral ART regimen must include at least 3 drugs with 2 or more drugs predicted to be fully active, including a boosted protease inhibitor (PI) and/or an integrase strand transfer inhibitor (INSTI)

Drug: Oral RPV

RPV 25 mg tablets

Other Name: Rilpivirine
Drug: Oral CAB

CAB 30 mg tablets

Other Name:
  • Cabotegravir
  • GSK1265744

Drug: RPV-LA Loading Dose

900 mg administered as one 3 mL (900 mg) intramuscular injection in the gluteal muscle

Other Name: Rilpivirine Long-Acting Injectable
Drug: CAB-LA Loading Dose

600 mg administered as one 3 mL (600 mg) intramuscular injection in the gluteal muscle

Other Name: Cabotegravir Long-Acting Injectable
Drug: RPV-LA Maintenance Dose

600 mg administered as one 2 mL (600 mg) intramuscular injection in the gluteal muscle

Other Name: Rilpivirine Long-Acting Injectable
Drug: CAB-LA Maintenance Dose

400 mg administered as one 2 mL (400 mg) intramuscular injection in the gluteal muscle

Other Name: Cabotegravir Long-Acting Injectable

Detailed Description:

This study will compare the efficacy, safety, and durability of two different strategies to treat participants with a history of sub-optimal adherence and control of their HIV infection: long-acting (LA) antiretroviral therapy (ART) with rilpivirine (RPV) LA and cabotegravir (CAB) LA versus all-oral standard of care (SOC).
The study includes four steps. In Step 1, participants will receive a SOC oral induction regimen consisting of an ART regimen that involves at least 3 drugs for 24 weeks. Participants who achieve milestones will receive conditional economic incentives at Weeks 2, 4, 8, 12, 16, and 20.
In Step 2, eligible participants will be randomized to receive either oral RPV + oral CAB for 4 weeks followed by RPV-LA + CAB-LA every 4 weeks for 48 weeks or to continue on SOC for 52 weeks.
At the completion of Step 2, eligible participants randomized to SOC will have the option to register to Step 3 and receive LA ART, which includes oral RPV + oral CAB for 4 weeks followed by RPV-LA + CAB-LA every 4 weeks for 48 weeks. Participants already receiving RPV-LA + CAB-LA in Step 2 will continue on this regimen in Step 3 for 52 weeks.
Eligible participants will enter Step 4 and be followed for 52 weeks on locally sourced oral ART.
Participants will be followed for up to a total of 180 weeks. Study visits, which will occur throughout the study, may include physical examinations; blood, urine, and hair collection; liver function tests; questionnaires; and an electrocardiogram (ECG).

Eligibility

Eligibility

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

Criteria

Step 1 Inclusion Criteria

  • HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
    • NOTE: The term "licensed" refers to a FDA-approved kit, which is required for all IND studies.
    • WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
  • HIV-1 Plasma viral load (VL) greater than 200 copies/mL within 60 days prior to study entry by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.
  • Evidence of non-adherence to ART according to at least one of the following criteria:
    • Poor virologic response within 18 months prior to study entry (defined as less than 1 log10 decrease in HIV-1 RNA or HIV-1 RNA greater than 200 copies/mL at two time points at least 4 weeks apart) in individuals who have been prescribed ART for at least 6 consecutive months.
    • Lost to clinical follow-up within 18 months prior to study entry with ART non-adherence for greater than or equal to 6 consecutive months.
    • NOTE: Lost to clinical follow-up is defined as either no contact with provider or missed greater than or equal to 2 appointments in a 6-month period. ART non-adherence is defined as a lapse in ART greater than or equal to 7 days (consecutive or non-consecutive), in the 6-month period where they were lost to clinical follow-up per participant report.
  • No evidence of any clinically relevant RPV or INSTI resistance-associated mutations (see Manual of Procedures [MOPS] for list of exclusionary mutations) through commercially available genotypic (or phenotypic, if available) analyses from any laboratory that has a CLIA certification or its equivalent within 60 days of study entry (see protocol for more information), nor history of such mutations on review of prior resistance tests by the site investigator. Genotypic analysis using proviral (i.e., archived) DNA is not allowed.
  • Ability of site clinician, in conjunction with participant, to construct an oral induction antiretroviral (ARV) regimen that must include at least three ARVs of which at least two must be predicted to be fully active. The regimen must, include PI/cobi and/or an INSTI based on screening and/or historic resistance testing.
  • Laboratory values obtained within 60 days prior to study entry by any laboratory that has a CLIA certification or its equivalent:
    • Hemoglobin greater than or equal to 9.0 g/dL
    • Absolute neutrophil count (ANC) greater than or equal to 600/mm^3
    • Alanine aminotransferase (ALT) less than or equal to 3 x upper limit of normal (ULN)
    • Creatinine Clearance (CrCl) greater than or equal to 50 mL/min estimated by Cockcroft-Gault
    • NOTE: A calculator for estimating the CrCl can be found at www.fstrf.org/ACTG/ccc.html.
  • For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of less than or equal to 25 mIU/mL at screening. This will be repeated again at study entry.
    • NOTE: Female participants are considered to be NOT of reproductive potential if: 1) they have had amenorrhea for at least 12 consecutive months prior to study entry ((i.e., who have had no menses within 12 months prior to study entry), and have a documented follicle-stimulating hormone (FSH) greater than 40 IU/mL; OR 2) an FSH level is not available, but they have had 24 consecutive months of amenorrhea (in the absence of medications known to induce amenorrhea); OR 3) they report having undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation/hysteroscopic tubal occlusion).
  • Contraception requirements
    • Female Participants of Reproductive Potential: Female participants of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one of the listed highly effective methods for contraception from 30 days prior to the first dose of study medication, while receiving the study drugs, and for 30 days after stopping oral medications, or the duration specified in the product label if receiving study drugs not supplied by the study, or 52 weeks after stopping RPV-LA or CAB-LA. Acceptable methods of contraception include:
      • Contraceptive subdermal implant
      • Intrauterine device or intrauterine system
      • Combined estrogen and progestogen oral contraceptive
      • Injectable progestogen
      • Contraceptive vaginal ring
      • Percutaneous contraceptive patches
    • Female Participants Who Are Not of Reproductive Potential: Women who are not of reproductive potential are eligible to start study drugs without requiring the use of contraceptives. Any statement of self-reported sterility or that of her partner's must be entered in the source documents.
    • NOTE A: Acceptable documentation of lack of reproductive potential is the woman's self-reported history of surgical sterilization, menopause, or male partner's azoospermia.
    • NOTE B: ALL participants in the study should be counseled 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.
  • Age greater than or equal to 18 years.
  • Ability and willingness of participant or legal guardian/representative to provide written informed consent.

  • Step 1 Exclusion Criteria
  • Currently pregnant, planning to become pregnant during the study period, or currently breastfeeding.
  • Participants determined by the Site Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder.
    • NOTE: A participant 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 A5359 protocol leadership team (actg.leada5359@fstrf.org) prior to enrollment.
  • Advanced liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) OR history of liver cirrhosis.
  • Chronic Hepatitis C (HCV) with planned or anticipated use of anti-HCV therapy prior to the completion of Step 2.
  • History of or current active hepatitis B (HBV) infection defined as positive HBV surface antigen test or any detectable HBV DNA in participants with isolated HBcAb and HBV DNA as follows:
    • Participants positive for HBsAg are excluded
    • Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and any detectable 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.
  • Current or anticipated need for chronic anti-coagulation therapy.
  • Unwilling to receive injections, or unable to receive gluteal injections.
  • Tattoo or other condition over gluteus region, which may interfere with interpretation of injection site reaction.
  • Previous use of CAB.
  • Acute or serious illness requiring systemic treatment and/or hospitalization within 7 days prior to entry.
  • QTc greater than 450 ms using either Bazett or Fridericia method within 60 days prior to study entry: Whichever method is used at screening must be used throughout study period.
  • Any serious medical or psychiatric condition, which may render the participant unable to receive study medication in the opinion of the site investigator.
  • Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.
  • Requirement for any medication that is prohibited with a study medication (refer to protocol specific web page [PSWP]).

  • Step 2 Inclusion Criteria
  • HIV-1 RNA less than 50 copies/mL at Step 1, week 20, or HIV-1 RNA of 50-399 copies/mL at Step 1, week 20, followed by HIV-1 RNA less than 50 copies/mL by Step 1, week 24.

  • Step 2 Exclusion Criteria
  • Permanent discontinuation of study treatment for any reason during Step 1.
  • Participants who never started study treatment in Step 1 (see protocol for more information)

  • Step 3 Inclusion Criteria
  • Willingness to continue for those in Arm A or begin to receive LA ART for those in Arm B.
  • Arm B participants: HIV-1 RNA less than 50 copies/mL at Step 2, week 48, or HIV-1 RNA of 50-399 copies/mL at Step 2, week 48, followed by HIV-1 RNA less than 50 copies/mL by Step 2, week 52.

  • Step 3 Exclusion Criteria
  • Permanent discontinuation of study treatment for any reason during Step 2.

  • Step 4 Inclusion Criteria
  • Any participant who has received at least one dose of CAB-LA or RPV-LA AND does not have access to commercially available LA ART,
  • OR does not wish to continue LA ART.

  • Step 4 Exclusion Criteria
  • There are no exclusion criteria for Step 4.

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: NCT03635788

Locations

United States, Alabama
Alabama CRS
Birmingham, Alabama, United States, 35294
United States, California
University of Southern California CRS
Los Angeles, California, United States, 90033-1079
UCLA CARE Center CRS
Los Angeles, California, United States, 90035
UCSD Antiviral Research Center CRS
San Diego, California, United States, 92103
Ucsf Hiv/Aids Crs
San Francisco, California, United States, 94110
Harbor-UCLA CRS
Torrance, California, United States, 90502
United States, Colorado
University of Colorado Hospital CRS
Aurora, Colorado, United States, 80045
United States, Florida
Univ. of Florida Jacksonville NICHD CRS
Jacksonville, Florida, United States, 32209
United States, Georgia
The Ponce de Leon Center CRS
Atlanta, Georgia, United States, 30308-2012
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
Rush University CRS
Chicago, Illinois, United States, 60612
United States, Maryland
Johns Hopkins University CRS
Baltimore, Maryland, United States, 21205
United States, Massachusetts
Massachusetts General Hospital CRS (MGH CRS)
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital Therapeutics Clinical Research Site (BWH TCRS) CRS
Boston, Massachusetts, United States, 02115
United States, Missouri
Washington University Therapeutics (WT) CRS
Saint Louis, Missouri, United States, 63110-1010
United States, New Jersey
New Jersey Medical School Clinical Research Center CRS
Newark, New Jersey, United States, 07103
United States, New York
Jacobi Med. Ctr. Bronx NICHD CRS
Bronx, New York, United States, 10461
Weill Cornell Chelsea CRS
New York, New York, United States, 10010
Columbia P&S CRS
New York, New York, United States, 10032-3732
Weill Cornell Uptown CRS
New York, New York, United States, 10065
SUNY Stony Brook NICHD CRS
Stony Brook, New York, United States, 11794
United States, North Carolina
Chapel Hill CRS
Chapel Hill, North Carolina, United States, 27599
Greensboro CRS
Greensboro, North Carolina, United States, 27401
United States, Ohio
Cincinnati Clinical Research Site
Cincinnati, Ohio, United States, 45219
Case Clinical Research Site
Cleveland, Ohio, United States, 44106
Ohio State University CRS
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Penn Therapeutics, CRS
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh CRS
Pittsburgh, Pennsylvania, United States, 15213
United States, Rhode Island
The Miriam Hospital Clinical Research Site (TMH CRS) CRS
Providence, Rhode Island, United States, 02906
United States, Tennessee
Vanderbilt Therapeutics (VT) CRS
Nashville, Tennessee, United States, 37204
United States, Texas
Trinity Health and Wellness Center CRS
Dallas, Texas, United States, 75208
Houston AIDS Research Team CRS
Houston, Texas, United States, 77030
United States, Washington
University of Washington AIDS CRS
Seattle, Washington, United States, 98104-9929
Puerto Rico
Puerto Rico AIDS Clinical Trials Unit CRS
San Juan, Puerto Rico, 00935
San Juan City Hosp. PR NICHD CRS
San Juan, Puerto Rico, 00936

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
ViiV

Investigators

Study Chair: Jose Castillo-Mancilla, M.D. University of Colorado Hospital CRS
Study Chair: Aadia Rana, M.D. Alabama CTU
More Information

More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT03635788   History of Changes  
Other Study ID Numbers: ACTG A5359  
  30104  
Study First Received: August 15, 2018  
Last Updated: April 6, 2020  
Individual Participant Data    
Plan to Share IPD: Yes  

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

Additional relevant MeSH terms:
HIV Infections
Rilpivirine

ClinicalTrials.gov processed this data on April 08, 2020
This information is provided by ClinicalTrials.gov.