Safety, Tolerability and Acceptability of Long-Acting Cabotegravir (CAB LA) for the Prevention of HIV Among Adolescent Males

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.

Inclusion criteria

• Assigned male at birth (includes MSM, TGW, and gender non-conforming people)
• At enrollment, aged below 18 years
• At enrollment, body weight ≥ 35 kg (77 lbs.)
• Willing to provide informed consent for the study
• Self-reported sexual activity with a male in the past 12 months
• In general, good health, as evidenced by the following laboratory values

• Non-reactive/negative HIV test results
• Absolute neutrophil count > 799 cells/mm3
• Platelet count ≥ 100,000 cells/mm3
• Hemoglobin ≥ 11g/dL
• Calculated creatinine clearance ≥ 60 mL/minute using modified Schwartz equation (≤ grade 2)
• Alanine aminotransferase (ALT) < 2.0 times the upper limit of normal (ULN) and total bilirubin (Tbili) ≤ 2.5 x ULN
• Hepatitis B virus (HBV) surface antigen (HBsAg) negative and accepts vaccination
• Hepatitis C virus (HCV) Antibody negative
• Willing to undergo all required study procedures
• If currently on pre-exposure prophylaxis (PrEP) from a non-study source, willing to stop said PrEP prior to enrollment and agree to switch to oral CAB for the lead-in period and CAB LA injections.

Exclusion criteria

• Co-enrollment in any other HIV interventional research study or other concurrent studies which may interfere with this study (as provided by self-report or other available documentation)
• Past or current participation in HIV vaccine trial with exception for participants who can provide documentation of receipt of placebo
• Exclusively had sex with biological females in lifetime
• In the last 6 months (at the time of screening): active or planned use of any substance which would, in the opinion of the site investigator, would hinder study participation (including herbal remedies), as described in the Investigator's Brochure (IB) or listed in the Study Specific Procedures (SSP), and/ or Protocol Section 4.4
• Known history of clinically significant cardiovascular disease, as defined by history/evidence of symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease
• Inflammatory skin conditions that compromise the safety of intramuscular (IM) injections
• Tattoo or other dermatological condition overlying the buttock region that may interfere with interpretation of injection site reactions
• Current or chronic history of liver disease (e.g., non-alcoholic or alcoholic steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones, or cholecystectomy)
• Known history of clinically significant bleeding
• Surgically-placed or injected buttock implants or fillers, per self-report. Contact the CMC for guidance regarding questions about individual cases
• A history of seizure disorder, per self-report
• Medical, social, or other condition that, in the opinion of the site investigator, would interfere with the conduct of the study or the safety of the participant (e.g., provided by self-report, or found upon medical history and examination or in available medical records)
• Plans to move out of the geographic area within the next 18 months or otherwise unable to participate in study visits, according to the site investigator.