Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Males - A Sub-study of HPTN 083
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|ClinicalTrials.gov Identifier: NCT04692077|
Recruitment Status : Recruiting
First Posted : December 31, 2020
Last Update Posted : December 31, 2020
|Condition or disease||Intervention/treatment||Phase|
|HIV Infections||Drug: Cabotegravir (CAB) tablet Drug: CAB LA Drug: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) tablet||Phase 2|
The purpose of this study is to establish the minimum safety, tolerability and acceptability data needed to support the use of cabotegravir long-acting injection (CAB LA) in an adolescent population, potentially transforming the field of HIV prevention for young people.
This study will enroll healthy, HIV-uninfected adolescents assigned male at birth, including men who have sex with men (MSM), transgender women (TGW), and gender non-conforming people. The total participant commitment for the entire study is approximately 1.5 years.
This study will take place in three steps. In Step 1, participants will receive daily oral CAB tablets for 5 weeks. In Step 2, participants will receive a series of five intramuscular (IM) injections of CAB LA, administered at 8-week intervals after a 4-week loading dose (injections at Weeks 5, 9, 17, 25 & 33). A safety visit will follow each injection to ascertain safety data, including injection site reactions. In Step 3, all participants who have received at least one injection will be followed quarterly (every 3 months) for 48 weeks after their last injection. Participants will receive oral TDF/FTC for daily use for 48 weeks or may be provided the opportunity to enroll in a local open label study of CAB, if available.
Participants will attend about 18 study visits throughout the study. Visits may include physical examinations, blood collection, urine collection, rectal and oral pharyngeal swab collection, risk reduction and adherence counseling, and behavioral or acceptability assessments.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Males - A Sub-study of HPTN 083|
|Actual Study Start Date :||February 19, 2020|
|Estimated Primary Completion Date :||August 12, 2022|
|Estimated Study Completion Date :||August 12, 2022|
Experimental: CAB LA
In Step 1, participants will receive one CAB tablet orally every day for 5 weeks. In Step 2, participants will receive an intramuscular (IM) injection of CAB LA at Weeks 5, 9, 17, 25, and 33. In Step 3, participants will receive a TDF/FTC tablet orally every day for 48 weeks or may be offered the opportunity to join an open label CAB study instead, if such a study is being implemented in their area at the time.
Drug: Cabotegravir (CAB) tablet
30 mg tablets
Drug: CAB LA
Administered as one 3 mL (600 mg) IM injection in the gluteal muscle at two time points 4 weeks apart and every 8 weeks thereafter.
Drug: Tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) tablet
300 mg/200 mg fixed-dose combination tablets
- Safety endpoint: Proportion of participants experiencing any Grade 2 or higher clinical adverse events (AEs) and laboratory abnormalities among participants who receive at least one injection of CAB LA. [ Time Frame: Measured through participant's last study visit, up to 1.5 years after study entry. ]
- Tolerability endpoint: Proportion of participants who receive at least 1 injection and who discontinue receiving injections prior to the full course of injections due to intolerability of injection, frequency of injections or burden of study procedures. [ Time Frame: Measured through participant's last study visit, up to 1.5 years after study entry. ]
- Acceptability endpoint: Proportion of participants who complete all scheduled injections and proportion of participants who receive at least one injection whom would consider using CAB LA for HIV prevention in the future. [ Time Frame: Measured through participant's last study visit, up to 1.5 years after study entry. ]
- Plasma CAB Drug Measurements [ Time Frame: Measured through participant's last study visit, up to 1.5 years after study entry. ]CAB drug concentrations will be measured in plasma to generate CAB-LA concentration-time profiles among study participants. Measurements will occur at study visits during the injection phase of the study as well as during the pharmacologic "tail" phase.
- Proportion of participant-study visits above the protein-adjusted inhibitor concentration (90%; PA-IC₉₀) [ Time Frame: Measured through participant's last study visit, up to 1.5 years after study entry. ]CAB drug concentrations will be measured throughout the study, to determine the proportion of visits in which a participant remains above the 1x (0.166 mcg/mL), 4x (0.664 mcg/mL) and 8x (1.33 mcg/mL) PA-IC₉₀. Concentrations above the 3 PA-IC₉₀ are associated with rectal protection in a non-human primate study, and concentrations above the 8x PA-IC₉₀ are expected to be associated with protection in humans.
- Measurement of pharmacokinetic parameters, mean and median drug concentrations at each injection visit. [ Time Frame: Measured from the initial injection through Week 33. ]CAB drug concentrations will be measured throughout the study, and the study team will characterize variability in concentrations at each visit by determining mean and median concentrations, as well as associated deviations and %CVs.
- Terminal half-life estimates for CAB-LA. [ Time Frame: Measured through participant's last study visit, up to 1.5 years after study entry. ]CAB drug concentrations will be measured during the tail phase of the study, up to one year after a participant's last visit. This will allow the study team to estimate the terminal half-life of CAB-LA.
- Characterize CAB drug concentrations in individuals who acquire HIV. [ Time Frame: Measured through participant's last study visit, up to 1.5 years after study entry. ]CAB drug measurements will be conducted in all participants, including those who acquire HIV; these data will be used to determine the CAB drug concentration at the first HIV positive visit, and serve as a possible explanatory variable in potential HIV acquisition. Drug concentrations will be evaluated within the context of CAB's PA-IC₉₀.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04692077
|United States, Illinois|
|John H. Stroger Jr. Hosp. of Cook County ATN CRS||Recruiting|
|Chicago, Illinois, United States, 60612|
|Contact: Kelly Bojan, R.N., C.F.N.P., A.P.N., D.N.P. 312-572-4571 firstname.lastname@example.org|
|United States, Massachusetts|
|The Fenway Institute ATN CRS||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Marcy Gelman, R.N., M.S.N., M.P.H., A.R.N.P. 617-927-6021 email@example.com|
|United States, Tennessee|
|St. Jude Children's Research Hosp. ATN CRS||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Mary E. Dillard, B.S.N. 901-495-4083 firstname.lastname@example.org|
|Study Chair:||Sybil Hosek, PhD||Stroger Hospital of Cook County|
|Study Chair:||Lynda Stranix-Chibanda, MBChB, MMED||University of Zimbabwe College of Health Sciences|