Injectable Cabotegravir + Rilpivirine for HIV

Recruiting in Palo Alto (17 mi)

+94 other locations

Age: 18+

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: ViiV Healthcare

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?The First Long-Acting Injectable Regimen (FLAIR) study is being conducted to establish if human immunodeficiency virus type-1 (HIV-1) infected adult participants whose virus is virologically suppressed on an integrase inhibitor single tablet regimen (INI STR) will remain suppressed after switching to a two-drug intramuscular (IM) long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In this study, the INI STR will be limited to abacavir/dolutegravir/lamivudine (ABC/DTG/3TC). FLAIR is a Phase 3, multi-phase, randomized, open label, active-controlled, multicenter, parallel-group, non-inferiority study in HIV-1, anti-retroviral therapy (ART)-naïve adult participants. This study is designed to demonstrate the non-inferior antiviral activity of switching to a two drug CAB LA 400 mg + RPV LA 600 mg regimen every 4 weeks (Q4W: monthly) compared to remaining on ABC/DTG/3TC over 48 weeks (4 weeks oral CAB + RPV, 44 weeks LA therapy). Participants who are HLA-B\*5701 positive at Screening may enroll into the study and receive DTG plus a non-abacavir containing dual nucleoside reverse transcriptase inhibitor (NRTI) regimen. Eligible participants will enroll into the Induction Phase of the study and receive ABC/DTG/3TC for 20 weeks (Week \[-20\] to Day 1). Participants who have an HIV 1 ribose nucleic acid (RNA) \<50 copies per milliliter (c/mL) at Week (-4) will be randomized (1:1) into the Maintenance Phase at Day 1 to either continue ABC/DTG/3TC or to discontinue ABC/DTG/3TC and begin oral therapy with CAB 30 mg + RPV 25 mg once daily for approximately 4 Weeks, followed by monthly CAB LA + RPV LA injections from visit Week 4b until study completion or withdrawal. Participants who successfully complete Week 100 (without meeting study defined withdrawal criteria and who remain virologically suppressed through Week 96: HIV-1 RNA \<50 c/mL) will be given the option to switch to the LA arm in the Extension Phase (using an optional oral lead-in with CAB + RPV) or be withdrawn from the study. Participants will continue to receive injections every 4 weeks during the Extension Phase until CAB LA and RPV LA are either locally approved and commercially available, the participant no longer derives clinical benefit, the participant meets a protocol-defined reason for discontinuation, or until development of either CAB LA or RPV LA is terminated.

Eligibility Criteria

Adults with HIV-1 who haven't been treated for it before can join this trial. They must have a certain level of virus in their blood and be able to consent to the study's rules. Women can't be pregnant or breastfeeding, and everyone must meet specific contraception requirements. People with severe allergies to study drugs, serious health conditions, or those at risk of suicide are not eligible.

Inclusion Criteria

I am over 18, HIV positive, and have never taken antiretroviral therapy.

Exclusion Criteria

I do not have liver disease, cirrhosis, pancreatitis, or biliary abnormalities.

I am allergic to the study drug or similar medications.

I am not taking any medications known to cause heart rhythm problems.

I have a serious heart condition.

I have moderate to severe liver problems.

I need or will need long-term blood thinners.

My kidney function is reduced, with a creatinine clearance below 50 mL/min.

I am not pregnant, breastfeeding, nor planning to during the study.

I cannot use certain HIV medications due to my HLA-B*5701 status.

I have tested positive for Hepatitis B.

My HIV does not show resistance to most NNRTIs or INIs, except K103N.

I haven't taken any experimental drugs or vaccines recently.

Participant Groups

The FLAIR study is testing if a long-acting injectable combo (cabotegravir and rilpivirine) keeps HIV suppressed as well as a daily pill regimen does after initial treatment success. Participants will first take pills for 20 weeks; then they'll either continue pills or switch to monthly injections for up to 100 weeks.

2Treatment groups

Experimental Treatment

Active Control

Group I: CAB LA + RPV LA every 4 weeksExperimental Treatment4 Interventions

After Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will receive oral CAB 30 mg + RPV 25 mg once daily for approximately four weeks. At visit Week 4b subjects will receive an initial loading dose of CAB LA (600 mg) and RPV LA (900 mg) at Week 4b. From Week 8 onwards, subjects will receive CAB LA (400 mg) + RPV LA (600 mg) injections every 4 weeks.

Group II: ABC / DTG / 3TC (600 mg/50mg/300mg) once dailyActive Control2 Interventions

After the Induction Phase with ABC/DTG/3TC (or DTG + two NRTIs), eligible participants will continue to receive oral ABC/DTG/3TC (or DTG + two NRTIs) initiated during the Induction Phase for 100 weeks. At the end of the Maintenance Phase, eligible participants receiving ABC/DTG/3TC (or DTG + two NRTIs) have the option to continue in the study by switching to CAB LA + RPV LA in the Extension Phase. These participants will transition to LA dosing at either Week 100 (direct to inject) or Week 104b (if using optional oral lead-in with CAB 30 mg + RPV 25 mg once daily).

Cabotegravir is already approved in European Union, United States, Canada, Japan, Australia for the following indications:

🇪🇺 Approved in European Union as Vocabria for: