Improving HIV-1 Control in Africa with Long Acting Antiretrovirals

NCT05546242 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: TMC278LAHTX3005
• Study Type: interventional
• Target: 540
• Locations: 3 countries
• Sites: 7

Brief 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.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• HIV-1 viral load at 12 months

  Proportion with plasma HIV-1 viral load (VL) \<50 c/mL at 12 months (by Food and Drug Administration \[FDA\] snapshot algorithm)

  12 months

Secondary Outcomes (16)

• Confirmed virologic failure on 2 consecutive occasions

  12 months

• Confirmed virologic failure on 2 consecutive occasions

  24 months

• Lost to follow up

  12 months

• Lost to follow up

  24 months

• HIV-1 viral load <200c/mL

  12 months

Other Outcomes (10)

• Change in health-related quality of life

  12 months and 24 months

• Change in health-related quality of life

  12 months and 24 months

• Change in health-related quality of life

  6 months, 12 months and 18 months

Study Arms (2)

CAB LA + RPV LA Arm

EXPERIMENTAL

The first 4 weeks of the treatment differ depending on whether participant opts for direct to injection (DTI) or Oral lead-in (OLI). DTI: participants will remain on daily oral ART for 4weeks after randomization and will receive the 1st injection of IM CAB LA 600mg+RPV LA 900mg at the Month 1 visit. 2nd injections administered at Month 2, followed by maintenance injections every 2 months (Q2M) OLI: participants will receive the study intervention in 2 phases: 1. Participants will receive CAB 30mg+RPV 25mg OD for 4weeks to be taken daily with food. The purpose of the optional OLI Phase is to allow an opportunity for participants to assess tolerability of the combination prior to administration of the injectables. There is no proven benefit to this approach 2. After 4weeks participants return for the Month 1 visit to receive the 1st IM CAB LA 600mg+RPV LA 900mg injections. The 2nd injections administered at Month 2 and then continuation injections will be administered Q2M

Drug: Cabotegravir/Rilpivirine

ART Group

ACTIVE COMPARATOR

Participants will take a daily oral combination of 2 NRTIs plus DTG 50mg. Ideally, the single tablet fixed-dose combination regimen of (tenofovir disoproxil fumarate \[TDF\] 300 mg + lamivudine \[3TC\] 300 mg (or emtricitabine \[FTC\] 200 mg) + DTG 50 mg) will be used as per local country guidelines up to Month 24. If there are preexisting reasons why TDF or 3TC cannot be used as the NRTI backbone then alternative NRTIs are acceptable. Participants will be permitted to switch daily oral ART drugs in case of toxicity, after discussion with the coordinating center.

Drug: Antiretroviral

Interventions

Cabotegravir/Rilpivirine DRUG

injectable long-acting cabotegravir 600mg + long-acting rilpivirine 900mg administered every 2 months

Also known as: Vocabria/Rekambys

CAB LA + RPV LA Arm

Antiretroviral DRUG

Oral antiretroviral therapy in the form of 2NRTIs + dolutegravir 50mg administered daily

Also known as: 2NRTIs + dolutegravir 50mg once daily

ART Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age and above
• HIV-1 infection confirmed in clinic records or by study team.
• Two consecutive HIV-1 VL \<200 copies/mL ≥3 months apart prior to randomization.
• On an oral regimen of 2NRTI + DTG as part of first line ART
• Is identified as a participant with a history of, sub-optimal ART adherence or engagement in care based on one or more of the following criteria:
• Documented detectable HIV-1 VL (\>1000 c/mL) on all-oral ART (EFV/NVP or DTG-based) in the prior 2 years despite being ART-experienced for
• ≥3 months.
• History of being lost to follow-up from care (\>4 weeks elapsed since a missed scheduled clinic appointment or refill in the prior 2 years).
• Failed to link to HIV care despite ≥3 months elapsed since HIV diagnosis.
• Females: human chorionic gonadotrophin (HCG) negative and willing to use one highly effective form of contraception if woman of reproductive potential
• Must sign informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
• Willing and able to attend all clinic appointments.

You may not qualify if:

• Not virologically suppressed (VL\<200 c/mL) for ≥3 months at the end of the screening process.
• Previous use, or intention to use, protease inhibitor-based ART at any time.
• Evidence of prior HIV-1 resistance test with NNRTI drug resistance mutations (other than K103N) and/or INSTI drug resistance mutations.
• Unwillingness to receive 2 injections on a 2 monthly basis.
• Unwilling to use a form of contraception.
• Pregnant, breastfeeding or planning to become pregnant during the study period.
• Requires tuberculosis therapy or other drug with clinically relevant drug interaction
• High risk of seizures, including participants with an unstable or poorly controlled seizure disorder.
• Has active TB or other mycobacterial disease and requires treatment.
• Advanced liver disease, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or history of cirrhosis.
• Chronic Hepatitis C with planned or anticipated use of Hep C therapy
• Evidence of hepatitis B virus (HBV) infection based on the results of testing at Screening for Hepatitis B surface antigen (HBsAg), Hepatitis B core antibody (HBcAb), Hepatitis B surface antibody (HBsAb) as follows:
• Participants positive for HBsAg are excluded
• Participants negative for HBsAg but positive for HBcAb, with no evidence of HBsAb are excluded NOTE: Participants positive for HBcAb due to prior infection (negative HBsAg status) and with evidence of HBsAb have some immunity to HBV and have low risk of reactivation so are not excluded.
• Current or anticipated need for chronic anticoagulation therapy.

Sponsors & Collaborators

• MRC/UVRI and LSHTM Uganda Research Unit: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (7)

Jaramogi Oginga Odinga Teaching & Referral Hospital

Kisumu, Kenya

Location

Kenyatta National Hospital

Nairobi, Kenya

Location

Desmond Tutu Health Foundation

Cape Town, South Africa

Location

CAPRISA

Durban, South Africa

Location

Entebbe Grade A Hospital

Entebbe, Uganda

Location

JCRC Fort Portal

Fort Portal, Uganda

Location

Infectious Diseases Institute

Kampala, Uganda

Location

Related Publications (1)

• Tumusiime VB, Ruzagira E, Norcross C, Eshun-Wilsonova I, Kitonsa J, Bahemuka UM, Grint D, Kimbugwe G, Kakande A, Lawrence DS, Mwendia F, Van Solingen R, Van Eygen V, Addo Boateng F, Cresswell F; IMPALA study team. Efficacy and Safety of Long-acting Injectable Cabotegravir and Rilpivirine in Improving HIV-1 Control in sub-Saharan Africa: Protocol for a Phase 3b Open-Label Randomized Controlled Trial (IMPALA). Wellcome Open Res. 2025 Mar 28;10:166. doi: 10.12688/wellcomeopenres.23363.1. eCollection 2025.

  PMID: 41040645 DERIVED

MeSH Terms

Interventions

cabotegravir; Rilpivirine; Anti-Retroviral Agents; dolutegravir

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antiviral Agents; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Fiona Cresswell, MBChB, PhD

  MRC/UVRI & LSHTM

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: parallel open-label phase 3b study. Participants will be randomised to continuing current therapy or switching to injectable therapy.

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: September 19, 2022
• Study Start: December 8, 2022
• Primary Completion: April 1, 2025
• Study Completion: March 1, 2026
• Last Updated: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (2); KE (2); UG (3)