NCT05546242

Improving HIV-1 Control in Africa with Long Acting Antiretrovirals

A Phase 3b Randomised, Multicentre, Open-label Study Evaluating the Effectiveness of Switching to Two-monthly Long-acting Injectable Cabotegravir and Rilpivirine from First-line Oral Antiretroviral Therapy in HIV-1 Positive Virologically Suppressed Adults with a History Of, or At Risk Of, Sub-optimal HIV Control in Sub-Saharan Africa

• Status: Active Not Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 540 (actual)
• Sponsor: MRC/UVRI and LSHTM Uganda Research Unit · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

IMPALA is a randomized, open-label, multicenter, interventional study of 540 virologically suppressed HIV-1 infected adults who have a history of sub-optimal adherence to daily oral ART and/or engagement in HIV care. The study will seek to demonstrate non-inferior antiviral effectiveness of the 2-monthly long-acting injectable combination of cabotegravir/rilpivirine as compared to continuation of first line oral antiretroviral therapy.

Detailed description

IMPALA is a randomized, open-label, multicenter, interventional study of 540 virologically suppressed (\<200 c/mL) HIV-1 infected adults (18 years or older) who have a history of sub-optimal adherence to daily oral ART and/or engagement in HIV care. IMPALA seeks to demonstrate the non-inferior antiviral effectiveness of switching to long acting injectable rilpivirine (RPV LA) plus long acting injectable cabotegravir (CAB LA) given every 2 months (Q2M CAB LA + RPV LA) by IM compared to the continuation of first-line daily oral ART containing 2 nucleoside reverse transcriptase inhibitor (NRTIs) plus an integrase strand transfer inhibitor (INSTI; dolutegravir \[DTG\]). After providing written informed consent, participants will be evaluated for eligibility during the screening period. Participants who are viremic (HIV VL \>200 c/mL) at the time of screening will be virologically suppressed (for \>3 months) on a regimen of 2 NRTIs plus DTG prior to randomization. On Day 1 virologically suppressed (\<200 c/mL for at least 3 months) individuals will be randomized 1:1 to either continue daily oral ART (2 NRTI + DTG, control arm), or switch to Q2M CAB LA + RPV LA IM, the intervention arm. Those randomized to the intervention arm will be offered either optional oral lead-in (OLI) of 1 month daily oral CAB and RPV or a direct to injection (DTI) approach. This decision to dose with or without an OLI Phase will be determined by the study participant following the informed consent discussion with the investigator. The total duration of the study will be 24 months. Any participant who has received at least a single dose of CAB LA + RPV LA and discontinues the regimen for any reason before Month 24 must start suppressive daily oral ART within 2 months of the last injection. There will be an optional real-world extension phase, provided the regimen is deemed to be non-inferior at Month 12 and 24.

Conditions

• HIV-1-infection

Interventions

Type	Name	Description
DRUG	Cabotegravir/Rilpivirine	injectable long-acting cabotegravir 600mg + long-acting rilpivirine 900mg administered every 2 months
DRUG	Antiretroviral	Oral antiretroviral therapy in the form of 2NRTIs + dolutegravir 50mg administered daily

Timeline

• Start date: 2022-12-08
• Primary completion: 2025-04-01
• Completion: 2026-03-01
• First posted: 2022-09-19
• Last updated: 2024-09-27

Locations

7 sites across 3 countries: Kenya, South Africa, Uganda