More Options for Children and Adolescents (MOCHA): Oral and Long-Acting Injectable Cabotegravir and Rilpivirine in HIV-Infected Children and Adolescents

IMPAACT 2017 was a Phase I/II, multi-center, open-label, non-comparative dose-finding study with the primary objective of evaluating the safety, acceptability, tolerability, and PK of oral cabotegravir (CAB) and long-acting cabotegravir (CAB LA) as well as long-acting rilpivirine (RPV LA) in adolescents living with HIV-1, who are 12 to \<18 years of age, ≥35kg, and virologically suppressed.

The study design included two cohorts of participants and five study steps. In Cohort 1, Step 1 participants received either oral CAB or oral rilpivirine (RPV) for at least four weeks and up to six weeks (maximum). In Cohort 1, Step 2 participants received intramuscular injectable formulations of the study products, either CAB LA or RPV LA. Cohort 1 participants were assigned either CAB (Cohort 1C) or RPV (Cohort 1R) based on their pre-study combination Antiretroviral Therapy (cART) regimen. Participants on a PI-based and/or NNRTI-based cART regimen were assigned to Cohort 1C, and participants on a non-boosted INSTI-based cART regimen were assigned to Cohort 1R. All participants continued their pre-study cART regimen during Cohort 1.

During Cohort 2, all participants discontinued their pre-study cART regimen and received both study products, CAB and RPV, at the doses established in Cohort 1. Cohort 2 participants enrolled to either Cohort 2A to receive both oral CAB + oral RPV (Step 3) followed by both CAB LA + RPV LA (Step 4) or Cohort 2B to directly receive both CAB LA + RPV LA without an oral lead-in phase (Step 5). If eligible, Cohort 1 participants were able to enroll into Cohort 2 (i.e., Cohort 1 Rollover). However, Cohort 2 participants who were not previously enrolled in Cohort 1 (i.e., Cohort 1-Naïve) were the primary group for analyses and conclusions. No participants enrolled into Cohort 2B, direct to injection (Step 5). Therefore, all references to Cohort 2 refer to Cohort 2A (Steps 3 and 4).

Two interim analyses were planned. The first interim analysis established the doses for Cohort 2 and determined whether to open Cohort 2 to Cohort 1 participants who met criteria to enter Cohort 2. The second interim analysis provided justification to open Cohort 2 to additional participants who were not previously enrolled in Cohort 1. A final analysis of Cohort 1 data was performed to confirm the final doses for Cohort 2.

Safety and PK evaluations were performed during Steps 1-5 and long-term safety follow-up (LSFU). Antiviral activity assessments were performed during Steps 1-5. Acceptability and tolerability were assessed during Steps 1-5 and LSFU, with all participants completing quantitative questionnaires and a subset of participants completing in-depth qualitative interviews. Additionally, parents/caregivers of a subset of U.S. participants from U.S. sites were also enrolled to complete a single in-depth qualitative interview. Because objectives related to parents/caregivers were exploratory, these outcomes are not described here.