Background:
Long-acting (LA), intramuscular (IM) cabotegravir (CAB) + rilpivirine (RPV) constitutes the first LA combination antiretroviral treatment (ART) regimen for people with HIV-1. The goal of the ongoing IMPAACT 2017 study (MOCHA [More Options for Children and Adolescents]; NCT03497676) is to evaluate the safety, tolerability, and pharmacokinetics (PK) of this LA combination in virologically suppressed (HIV-1 RNA < 50 c/mL) adolescents. Here we present PK and safety data through the primary Week 24 timepoint and available safety data beyond Week 24.
Methods:
In this Phase I/II, open‐label, noncomparative trial, virologically suppressed adolescents (12 to <18 years of age; ≥35 kg) with HIV-1 switched from their pre-study ART to 4 weeks of daily oral CAB + RPV followed by 600 mg CAB LA and 900 mg RPV LA IM (3 mL each) in the contralateral gluteus medius per the every 2-month dosing regimen. The 1st and 2nd injections were 4 weeks apart, with subsequent injections every 8 weeks.
Results:
144 participants were enrolled at 18 sites in 5 countries. Median (min, max) age was 15 years (12, 17), body mass index 19.5 kg/m2 (16, 34), weight 48 kg (35, 101), 49% male and 74% Black or African American. Most participants received ≥1 injection (142/144) and completed the Week 24 visit (141/144); mean (standard deviation) study duration was 56 weeks (13). No deaths or adverse events (AEs) leading to study drug discontinuation occurred; no serious AEs attributable to study product occurred. Through Week 24, 16/144 (11%) had a ≥ Grade 3 AE, most common being increases in blood creatine phosphokinase (n=6) and systolic blood pressure (n=3); none of these non-injection site reaction (ISR) AEs were considered study drug related. For all safety data, 49/142 (35%) participants reported an ISR, most (86%) ISRs resolved within 7 days and were Grade 1 (91%). Two of 144 (1%) participants experienced a drug-related ≥ Grade 3 AE (injection site pain and abscess [n=1]; injection site abscess [n=1]). The outcome of the single unintended pregnancy in a study participant was a healthy live birth. There was no virologic failure through Week 24. The median (5%, 95%) Week 24 predose concentrations for CAB [2.34 µg/mL (1.11, 4.15)] and RPV [49.5 ng/mL (25.9, 78.1)] were similar to those in adults (Figure). One participant had low CAB concentration at Week 24 (0.03 µg/mL).
Conclusions:
IMPAACT 2017 (MOCHA) data support using CAB-LA plus RPV-LA every 2 months in virologically suppressed adolescents.
