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Clinical Trial
. 2025 Mar;12(3):e191-e200.
doi: 10.1016/S2352-3018(24)00344-8.

Safety of combined long-acting injectable cabotegravir and long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study

Carolyn Bolton Moore  1 , Kristin Baltrusaitis  2 , Brookie M Best  3 , John H Moye  4 , Ellen Townley  5 , Avy Violari  6 , Barbara Heckman  7 , Sarah Buisson  8 , Rodica M Van Solingen-Ristea  9 , Edmund V Capparelli  3 , Mark A Marzinke  10 , Elizabeth D Lowenthal  11 , Shawn Ward  12 , Chelsea Krotje  7 , Ryan Milligan  12 , Allison L Agwu  10 , Jenny Huang  13 , S Y Amy Cheung  14 , Cynthia McCoig  15 , Dwight E Yin  5 , Gilly Roberts  16 , Herta Crauwels  9 , Veerle Van Eygen  9 , Sara Zabih  17 , Gaerolwe Masheto  18 , Pradthana Ounchanum  19 , Linda Aurpibul  20 , Violet Korutaro  21 , Aditya H Gaur  22 ; IMPAACT 2017 Collaborators for the IMPAACT 2017 Team
Collaborators, Affiliations
Clinical Trial

Safety of combined long-acting injectable cabotegravir and long-acting injectable rilpivirine in virologically suppressed adolescents with HIV (IMPAACT 2017/MOCHA): a phase 1/2, multicentre, open-label, non-comparative, dose-finding study

Carolyn Bolton Moore et al. Lancet HIV. 2025 Mar.

Abstract

Background: Long-acting cabotegravir and long-acting rilpivirine constitute a completely intramuscular antiretroviral therapy (ART) regimen for adults with HIV. We aimed to assess the safety, antiviral activity, and pharmacokinetics of oral cabotegravir and rilpivirine followed by a combination of long-acting cabotegravir and long-acting rilpivirine in virologically suppressed adolescents with HIV.

Methods: The IMPAACT 2017/MOCHA study is a phase 1/2, multicentre, open-label, non-comparative, dose-finding trial being conducted at 18 sites across Botswana, South Africa, Thailand, Uganda, and the USA. In cohort 2 of this study, adolescents (aged 12-18 years; weight ≥35 kg) with HIV and no serious comorbidities who were receiving stable combination ART with confirmed virological suppression and had either previously enrolled in the first cohort or had not previously participated in the study were eligible for inclusion. Participants stopped their background combination ART and received oral cabotegravir 30 mg once daily and oral rilpivirine 25 mg once daily orally for 4-6 weeks, followed by long-acting injectable cabotegravir 600 mg (3 mL) and long-acting injectable rilpivirine 900 mg (3 mL) intramuscularly at weeks 4 and 8, and every 8 weeks thereafter. The primary outcome was safety, including all adverse events, at week 24. Primary safety outcome measures were summarised as frequencies, percentages, and exact Clopper-Pearson 95% CIs in the evaluable analysis population, which included participants who were treated exclusively with the regimen and either completed all scheduled treatments or experienced severe adverse events, permanently discontinued the treatment, or died, whichever occurred first; and in the all-treated analysis population, which included all participants who received at least one dose of any study product. This study is registered with ClinicalTrials.gov (NCT3497676) and is ongoing.

Findings: Between July 26, 2021, and Aug 27, 2022, 44 (80·0%) of 55 adolescents who participated in cohort 1 and 100 (87·0%) of 115 screened study-naive adolescents were enrolled in cohort 2. 74 (51·4%) participants were female and 70 (48·6%) were male. Overall, 15 (10·8% [95% CI 6·2-17·2]) of all 139 participants in the evaluable analysis population had at least one adverse event of grade 3 or above by week 24. Among 142 participants who received at least one injection, 43 (30%) experienced at least one injection site reaction (ISR). All 106 ISRs were either grade 1 (98 [92·5%]) or grade 2 (eight [7·5%]), and 97 (91·5%) resolved within 7 days. No participant experienced a drug-related serious adverse event or prematurely discontinued treatment due to a drug-related adverse event.

Interpretation: Long-acting injectable cabotegravir and long-acting injectable rilpivirine, administered to adolescents at recommended adult dosages every 8 weeks, showed no unanticipated safety concerns in the 24 weeks following administration.

Funding: National Institutes of Health, ViiV Healthcare, and Johnson & Johnson.

Trial registration: ClinicalTrials.gov NCT03497676 NCT03497676.

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Conflict of interest statement

Declaration of interests KB, BMB, SB, BMB, AHG, CK, and MAM received IMPAACT Network grant funding from the National Institutes of Health (NIH) to support work on this protocol. KB, RM, and SW's institution receives funding from ViiV Healthcare. AHG's institution has a clinical trial agreement with the IMPAACT Network, ViiV Healthcare, and Janssen to provide support for this and other protocols. AHG received payment from ViiV Healthcare to serve on ViiV-sponsored advisory board meetings and as a panelist on an adolescent treatment and prevention webinar. CBM's institution received salary support from the IMPAACT Network for this protocol. DEY is an employee of the NIH. CM and GR are employees of ViiV Healthcare. SYAC, GR, and JH are employees of GSK. ALA and MAM's institutions received funding from Gilead, ViiV, and Merck. SW and RM's institution received funding from ViiV. KB's institution received funding from Gilead. MAM is a consultant for Bio-Rad and receives royalties from Elsevier. ALA is an expert witness and the chair of the HIV Medicine Association, a board member for The Well Project, and the board chair for Advocates for Youth. VVE is an employee of Janssen Pharmaceutical, which holds a US patent application or patent cooperation treaty for rilpivirine (international application number 62/870,413). CM and GR are shareholders of GSK. SYAC is an employee and shareholder of Certara and a consultant for GSK. HC, VVE, and RMVS-R are shareholders of Johnson & Johnson. HC, RMVS-R, and VVE are employees of Janssen. GR is a shareholder in AstraZeneca. DEY was formerly an unpaid advisor to the non-profit organisations Cover the Globe and Maipelo Trust. All other authors declare no competing interests.

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