Study to Assess the Effects of Cabotegravir (CAB) and Rilpivirine (RPV) Long-Acting (LA) Injections Following Sub-cutaneous (SC) Administration Compared With Intramuscular (IM) Administration in Adult Participants Living With Human Immunodeficiency Virus (HIV-1) Infection in the FLAIR Study

NCT05896748 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 201584-001
• Study Type: interventional
• Target: 94
• Locations: 6 countries
• Sites: 30

Brief Summary

This study will assess the pharmacokinetics, safety, tolerability, maintenance of virological suppression and patient reported outcomes for participants receiving CAB and RPV LA injections following SC administration in the anterior abdominal wall SC tissue compared with IM administration in the gluteus medius muscle in adult participants living with HIV-1 infection in the FLAIR study (NCT02938520).

Conditions

Human Immunodeficiency Virus Type 1 (HIV-1)

Keywords

Antiretroviral agent; Rilpivirine; Cabotegravir; FLAIR; Human immunodeficiency virus

Outcome Measures

Primary Outcomes (6)

• Concentrations at the End of the Dosing Interval (Ctau) of CAB LA 400 mg Following Administration CAB LA + RPV LA

  Blood samples were collected at indicated time points for PK analysis.

  At screening Week-4; Day 1, Week 4, Week 8 for SC injections; and Week 12 for Return to IM gluteal injection

• Ctau of RPV LA 600 mg Following Administration of CAB LA + RPV LA

  Blood samples were collected at indicated time points for PK analysis.

  At screening Week-4; Day 1, Week 4, Week 8 for SC abdominal injections; and Week 12 for Return to IM gluteal injection

• Maximum Plasma Concentration (Cmax) One Week Post Dose of CAB LA 400 mg Following Administration of CAB LA + RPV LA

  Blood samples were collected at indicated time points for PK analysis.

  At screening week -3; Week 1, Week 5, Week 9 for SC abdominal injections; and Week 13 for Return to IM gluteal injection

• Cmax One Week Post Dose of RPV LA 600 mg Following Administration of CAB LA + RPV LA

  Blood samples were collected at indicated time points for PK analysis.

  At screening Week -3; Week 1, Week 5, Week 9 for SC abdominal injections; and Week 13 for Return to IM gluteal injection

• Area Under the Plasma Concentration-time Curve From 0 Through the End of Dosing Interval (AUC[0-tau]) of CAB LA 400 mg Following Administration of CAB LA + RPV LA

  Blood samples were collected at indicated time points for PK analysis.

  At screening Week-4; Day 1, Week 4, Week 8 for SC abdominal injections; and Week 12, for Return to IM gluteal injection

• AUC[0-tau] of RPV LA 600 mg Following Administration of CAB LA + RPV LA

  Blood samples were collected at indicated time points for PK analysis.

  At screening Week-4; Day 1, Week 4, Week 8 for SC abdominal injections; and Week 12 for Return to IM gluteal injection

Secondary Outcomes (40)

• Number of Participants With Injection Site Reactions (ISRs) and by Maximum Severity - SC Injection Phase

  From Day 1 Up to Week 12

• Number of Participants With Adverse Events of Special Interest (AESI) Based on Maximum Severity Grade - SC Injection Phase

  From Day 1 Up to Week 12

• Number of Participants Who Discontinue Treatment Due to ISRs and AESIs - SC Injection Phase

  From Day 1 Up to Week 12

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) From the Last IM Gluteal Injection in Screening Phase to the End of the SC Injection Phase

  From Week -4 Up to Week 12

• Change From Baseline in Chemistry Parameters Following Administration of SC Injection: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Creatine Phosphokinase

  Baseline (screening Week -4), Change from baseline (CFB) at Week 4, CFB at Week 8, and CFB at Week 12

Study Arms (1)

Cabotegravir Long Acting (CAB LA) 400 Milligrams (mg) + Rilpivirine Long Acting (RPV) LA 600 mg

EXPERIMENTAL

Participants received an intramuscular (IM) injection of CAB LA 400 mg and RPV LA 600 mg on week -4 during the Screening phase. Participants then received a sub-cutaneous (SC) injection of CAB LA 400 mg + RPV LA 600 mg on Day 1 of Week 1, Week 4 and Week 8 (once in every 4 weeks (Q4W)) for a total of 12 weeks during the SC abdominal Injection Phase. 4 weeks later, participants returned to the clinic for an IM gluteal injection (at Week 12) of CAB LA 400 mg + RPV LA 600 mg during the Return to Gluteal Injection Phase and subsequent gluteal injection occurred after Q4W at Week 16.

Drug: Cabotegravir - Injectable Suspension (CAB LA); Drug: Rilpivirine - Injectable Suspension (RPV LA)

Interventions

Cabotegravir - Injectable Suspension (CAB LA) DRUG

It is a sterile white to slightly pink suspension containing 200 mg/mL of CAB as free acid for administration by intramuscular (IM) injection. Each vial is for single-dose use containing a withdrawable volume of 2.0 mL, and does not require dilution prior to administration. CAB LA is composed of cabotegravir free acid, polysorbate 20, polyethylene glycol 3350, mannitol, and water for injection.

Cabotegravir Long Acting (CAB LA) 400 Milligrams (mg) + Rilpivirine Long Acting (RPV) LA 600 mg

Rilpivirine - Injectable Suspension (RPV LA) DRUG

It is a sterile white suspension containing 300 mg/mL of RPV as the free base. The route of administration is by intramuscular (IM) injection. Each vial contains a nominal fill of 2.0 mL, and does not require dilution prior to administration. RPV LA requires refrigeration and must be protected from light. RPV LA is composed of RPV free base, poloxamer 338, sodium dihydrogen phosphate monohydrate, citric acid monohydrate, glucose monohydrate, sodium hydroxide, water for injection.

Cabotegravir Long Acting (CAB LA) 400 Milligrams (mg) + Rilpivirine Long Acting (RPV) LA 600 mg

Eligibility Criteria

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

You may qualify if:

• Capable of giving signed informed consent (FLAIR and Sub-study specific informed consent)
• Eligible participants must have been on CAB LA + RPV LA regimen for a minimum of 12 months while on the FLAIR study. Any disruptions in dosing during FLAIR must be discussed with the Medical Monitor for a final determination of eligibility into the sub-study.
• Plasma HIV-1 RNA \<50 c/mL at Sub-Study Screening.
• History of Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) vaccination (or booster dosing) is allowed prior to sub study screening and will be allowed during the conduct of the sub-study as long as the vaccine (or boosters) are not administered within 14 days of virologic load (VL) assessments.
• HIV-1 infected antiretroviral therapy (ART)-naive men or women aged 18 years or greater at the time of signing the informed consent.
• HIV-1 infection as documented by Screening plasma HIV-1 RNA \>=1000 cubic (c)/mL
• Female Participants: A female participant is eligible to participate if she is not pregnant at Screening and first day of Induction Phase (as confirmed by a negative serum human chorionic gonadotrophin \[hCG\] test), not lactating, and at least one of the following conditions applies
• Non-reproductive potential defined as:
• Pre-menopausal females with one of the following:
• Documented tubal ligation;
• Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion;
• Hysterectomy; Documented Bilateral Oophorectomy;
• Postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment.
• Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) from 30 days prior to the first dose of study medication, throughout the study, and for at least 30 days after discontinuation of all oral study medications and for at least 52 weeks after discontinuation of CAB LA and RPV LA.
• The investigator is responsible for ensuring that participants understand how to properly use these methods of contraception.

You may not qualify if:

• More than 1 plasma HIV-1 RNA measurement 50 c/mL to \<200 c/mL (virologic blip) within 24 weeks prior to sub-study Screening visit that was investigated and found NOT to be associated with alternative causes including recent vaccinations received within 4 weeks of the viral blip or NOT associated with intercurrent illness that developed within 2-4 weeks of the viral blip.
• All viral blips that occurred within 24 weeks prior to screening should be discussed with the Medical Monitor to assess whether such a participant can enroll into the sub-study.
• Any Suspected Virologic Failure (HIV-RNA 200 c/mL) as defined during FLAIR study.
• Participants planning to require oral bridging during participation in the FLAIR sub study.
• The participant has a tattoo or any dermatological condition overlying the abdominal or gluteal regions which may interfere with interpretation of injection site reactions.
• Any condition which, in the opinion of the Investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to receive study medication.
• Any woman of childbearing potential who is pregnant at screening will be excluded from entering the sub-study.
• Any women of childbearing potential who gets pregnant while on the sub-study will have to be withdrawn from the sub-study but will be allowed to transition back to the parent FLAIR study if a pregnancy specific Informed Consent Form (ICF) is signed, and commercial access is not available at the time of pregnancy
• Women who are pregnant, breastfeeding, or plan to become pregnant or breastfeed during the study.
• Participants with known moderate to severe hepatic impairment.
• Any pre-existing physical or mental condition (including substance abuse disorder) which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
• Participants determined by the Investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder. A participant with a prior history of seizure may be considered for enrollment if the Investigator believes the risk of seizure recurrence is low. All cases of prior seizure history should be discussed with the Medical Monitor prior to enrollment.
• Participant who, in the investigator's judgment, poses a significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
• The participant has a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reactions.
• 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 (anti HBc), Hepatitis B surface antibody (anti-HBs) and HBV Deoxyribonucleic acid (DNA) as follows:

Sponsors & Collaborators

• ViiV Healthcare: lead
• Janssen Pharmaceuticals: collaborator
• GlaxoSmithKline: collaborator

Study Sites (30)

GSK Investigational Site

Macon, Georgia, 31201, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Bellaire, Texas, 77401, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Fort Worth, Texas, 76104, United States

Location

GSK Investigational Site

Toronto, Ontario, M5G 1K2, Canada

Location

GSK Investigational Site

Osaka, 540-0006, Japan

Location

GSK Investigational Site

Tokyo, 162-8655, Japan

Location

GSK Investigational Site

Bloemfontein, Free State, 9301, South Africa

Location

GSK Investigational Site

Wentworth, KwaZulu-Natal, 4052, South Africa

Location

GSK Investigational Site

Durban, 4001, South Africa

Location

GSK Investigational Site

Barcelona, 08025, Spain

Location

GSK Investigational Site

Barcelona, 08907, Spain

Location

GSK Investigational Site

Bilbao, 48013, Spain

Location

GSK Investigational Site

Elche, 03203, Spain

Location

GSK Investigational Site

Ferrol, 15405, Spain

Location

GSK Investigational Site

Granada, 18016, Spain

Location

GSK Investigational Site

La Laguna-Tenerife, 38320, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Murcia, 30003, Spain

Location

GSK Investigational Site

Murcia, 30120, Spain

Location

GSK Investigational Site

Palma de Mallorca, 07198, Spain

Location

GSK Investigational Site

San Sebastián de los Reyes, 28702, Spain

Location

GSK Investigational Site

Santa Cruz de Tenerife, 38010, Spain

Location

GSK Investigational Site

Santander, 39008, Spain

Location

GSK Investigational Site

Birmingham, B9 5SS, United Kingdom

Location

GSK Investigational Site

Leeds, LS1 3EX, United Kingdom

Location

GSK Investigational Site

London, E1 1BB, United Kingdom

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 9, 2023
• Study Start: November 8, 2022
• Primary Completion: September 14, 2023
• Study Completion: September 14, 2023
• Last Updated: November 26, 2024
• Results First Posted: November 26, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.

Locations

CA (1); US (5); JP (2); ZA (3); ES (16); GB (3)