Study to Evaluate the Efficacy, Safety, and Tolerability of Long-acting Intramuscular Cabotegravir and Rilpivirine for Maintenance of Virologic Suppression Following Switch From an Integrase Inhibitor in HIV-1 Infected Therapy Naive Participants

Summary

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given the option to switch to the LA arm in the Extension Phase (using an optional oral lead-in with CAB + RPV) or be withdrawn from the study.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.

Timeline

Start

2016-10-27

Primary completion

2018-08-30

Completion

2029-12-31

Publications

• Background Orkin C, Arasteh K, Gorgolas Hernandez-Mora M, Pokrovsky V, Overton ET, Girard PM, Oka S, Walmsley S, Bettacchi C, Brinson C, Philibert P, Lombaard J, St Clair M, Crauwels H, Ford SL, Patel P, Chounta V, D'Amico R, Vanveggel S, Dorey D, Cutrell A, Griffith S, Margolis DA, Williams PE, Parys W, Smith KY, Spreen WR. Long-Acting Cabotegravir and Rilpivirine after Oral Induction for HIV-1 Infection. N Engl J Med. 2020 Mar 19;382(12):1124-1135. doi: 10.1056/NEJMoa1909512. Epub 2020 Mar 4.
• D'Amico R, Han K, Min S, DeMoor R, St Clair M, Ford SL, Harrington C, Bernal-Morell E, Lombaard J, Crauwels H, Kolobova I, Patel N, Jamil N, Van Solingen-Ristea R, Acuipil C, Spreen W. Subcutaneous injections of cabotegravir plus rilpivirine long-acting in virally suppressed adults with HIV-1. AIDS. 2025 Dec 1;39(15):2182-2190. doi: 10.1097/QAD.0000000000004310. Epub 2025 Oct 21.
• Okesanya OJ, Ayeni RA, Amadin P, Ngwoke I, Amisu BO, Ukoaka BM, Ahmed MM, Oso TA, Musa SS, Lucero-Prisno DE. Advances in HIV Treatment and Vaccine Development: Emerging Therapies and Breakthrough Strategies for Long-Term Control. AIDS Res Treat. 2025 Jul 4;2025:6829446. doi: 10.1155/arat/6829446. eCollection 2025.
• Elliot ER, Polli JW, Patel P, Garside L, Grove R, Barnett V, Roberts J, Byrapuneni S, Crauwels H, Ford SL, Van Solingen-Ristea R, Birmingham E, D'Amico R, Baugh B, van Wyk J. Efficacy, Safety, and Pharmacokinetics by Body Mass Index Category in Phase 3/3b Long-Acting Cabotegravir Plus Rilpivirine Trials. J Infect Dis. 2024 Jul 25;230(1):e34-e42. doi: 10.1093/infdis/jiad580.
• Chounta V, Byrnes HF, Henry-Szatkowski M, Browning D, Donatti C, Lambert J. Psychometric Validation of the Perception of Injection (PIN) Questionnaire Using Data From Two Phase III, Open-Label, Active-Controlled, Non-Inferiority Studies in People Living With HIV. Adv Ther. 2023 Dec;40(12):5300-5314. doi: 10.1007/s12325-023-02656-1. Epub 2023 Sep 30.
• Moreno S, Rivero A, Ventayol P, Falco V, Torralba M, Schroeder M, Neches V, Vallejo-Aparicio LA, Mackenzie I, Turner M, Harrison C. Cabotegravir and Rilpivirine Long-Acting Antiretroviral Therapy Administered Every 2 Months is Cost-Effective for the Treatment of HIV-1 in Spain. Infect Dis Ther. 2023 Aug;12(8):2039-2055. doi: 10.1007/s40121-023-00840-y. Epub 2023 Jul 14.
• Masia M, Fernandez-Gonzalez M, Agullo V, Mascarell P, Padilla S, Garcia-Abellan J, Gutierrez F. Human Immunodeficiency Virus Type 1 RNA Levels in Rectal and Seminal Compartments After Switching to Long-Acting Cabotegravir Plus Rilpivirine: A Longitudinal Study. Clin Infect Dis. 2023 Feb 8;76(3):e748-e751. doi: 10.1093/cid/ciac676.
• Chounta V, Snedecor SJ, Wu S, Van de Velde N. Indirect comparison of 48-week efficacy and safety of long-acting cabotegravir and rilpivirine maintenance every 8 weeks with daily oral standard of care antiretroviral therapy in participants with virologically suppressed HIV-1-infection. BMC Infect Dis. 2022 May 4;22(1):428. doi: 10.1186/s12879-022-07243-3.
• Jeffrey JL, St Clair M, Wang P, Wang C, Li Z, Beloor J, Talarico C, Fridell R, Krystal M, White CT, Griffith S, D'Amico R, Smith K, Van Eygen V, Vingerhoets J, Vandermeulen K, Spreen W, van Lunzen J. Impact of Integrase Sequences from HIV-1 Subtypes A6/A1 on the In Vitro Potency of Cabotegravir or Rilpivirine. Antimicrob Agents Chemother. 2022 Mar 15;66(3):e0170221. doi: 10.1128/AAC.01702-21. Epub 2022 Jan 3.
• Orkin C, Bernal Morell E, Tan DHS, Katner H, Stellbrink HJ, Belonosova E, DeMoor R, Griffith S, Thiagarajah S, Van Solingen-Ristea R, Ford SL, Crauwels H, Patel P, Cutrell A, Smith KY, Vandermeulen K, Birmingham E, St Clair M, Spreen WR, D'Amico R. Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: week 124 results of the open-label phase 3 FLAIR study. Lancet HIV. 2021 Nov;8(11):e668-e678. doi: 10.1016/S2352-3018(21)00184-3. Epub 2021 Oct 14.
• Orkin C, Oka S, Philibert P, Brinson C, Bassa A, Gusev D, Degen O, Garcia JG, Morell EB, Tan DHS, D'Amico R, Dorey D, Griffith S, Thiagarajah S, St Clair M, Van Solingen-Ristea R, Crauwels H, Ford SL, Patel P, Chounta V, Vanveggel S, Cutrell A, Van Eygen V, Vandermeulen K, Margolis DA, Smith KY, Spreen WR. Long-acting cabotegravir plus rilpivirine for treatment in adults with HIV-1 infection: 96-week results of the randomised, open-label, phase 3 FLAIR study. Lancet HIV. 2021 Apr;8(4):e185-e196. doi: 10.1016/S2352-3018(20)30340-4.
• Rizzardini G, Overton ET, Orkin C, Swindells S, Arasteh K, Gorgolas Hernandez-Mora M, Pokrovsky V, Girard PM, Oka S, Andrade-Villanueva JF, Richmond GJ, Baumgarten A, Masia M, Latiff G, Griffith S, Harrington CM, Hudson KJ, St Clair M, Talarico CL, Patel P, Cutrell A, Van Eygen V, D'Amico R, Mrus JM, Wu S, Ford SL, Chow K, Roberts J, Wills A, Walters N, Vanveggel S, Van Solingen-Ristea R, Crauwels H, Smith KY, Spreen WR, Margolis DA. Long-Acting Injectable Cabotegravir + Rilpivirine for HIV Maintenance Therapy: Week 48 Pooled Analysis of Phase 3 ATLAS and FLAIR Trials. J Acquir Immune Defic Syndr. 2020 Dec 1;85(4):498-506. doi: 10.1097/QAI.0000000000002466.

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