A Sub-study of Cabotegravir (CAB) and Rilpivirine (RPV) in Human Immunodeficiency Viruses (HIV)-Infected Participants

NCT05896761 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 207966-001
• Study Type: interventional
• Target: 118
• Locations: 7 countries
• Sites: 32

Brief Summary

This sub-study will assess the pharmacokinetics (PK), safety, tolerability, virologic efficacy and health outcomes of CAB (GSK1265744) and RPV long acting (LA) in HIV-infected adult participants currently enrolled in the Antiretroviral Therapy as Long Acting Suppression every 2 Months (ATLAS2M \[A2M\]) study (NCT03299049).

Conditions

Human Immunodeficiency Virus Type 1 (HIV-1)

Keywords

Cabotegravir; Efficacy; Human immunodeficiency virus; Pharmacokinetic; Rilpivirine; Safety; Tolerability

Outcome Measures

Primary Outcomes (12)

• Concentration at End of Dosing Interval (Ctau) of CAB LA Following Administration of CAB LA + RPV LA Q8W

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

  Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)

• Concentration at End of Dosing Interval (Ctau) of RPV LA Following Administration of CAB LA + RPV LA Q8W

  Blood samples were collected for PK analysis.

  Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)

• Maximum Plasma Concentration (Cmax) of CAB LA Following Administration of CAB LA + RPV LA Q8W

  Blood samples were collected for PK analysis.

  Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)

• Maximum Plasma Concentration (Cmax) of RPV LA Following Administration of CAB LA + RPV LA Q8W

  Blood samples were collected for PK analysis.

  Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)

• Area Under the Concentration Curve From 0 Hours to the Time of Next Dosing (AUC [0-tau]) of CAB LA Following Administration of CAB LA + RPV LA Q8W

  Blood samples were collected for PK analysis.

  Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)

• Area Under the Concentration Curve From 0 Hours to the Time of Next Dosing (AUC [0-tau]) of RPV LA Following Administration of CAB LA + RPV LA Q8W

  Blood samples were collected for PK analysis.

  Weeks -8,-7,-4 and Pre-dose on Day 1(Pre-Thigh Gluteal Injection);2 Hours post-dose on Day 1,Pre-dose on Week 8,Weeks 1 and 4 post-dose(First Thigh Injection);2 Hours post-dose on Week 8 and Weeks 9, 12 post-dose,Pre-dose on Week 16(Last Thigh Injection)

• Concentration at End of Dosing Interval (Ctau) of CAB LA Following Administration of CAB LA + RPV LA Q4W

  Blood samples were collected for PK analysis.

  Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)

• Concentration at End of Dosing Interval (Ctau) of RPV LA Following Administration of CAB LA + RPV LA Q4W

  Blood samples were collected for PK analysis.

  Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)

• Maximum Plasma Concentration (Cmax) of CAB LA Following Administration of CAB LA + RPV LA Q4W

  Blood samples were collected for PK analysis.

  Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)

• Maximum Plasma Concentration (Cmax) of RPV LA Following Administration of CAB LA + RPV LA Q4W

  Blood samples were collected for PK analysis.

  Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)

• Area Under the Concentration Curve From 0 Hours to the Time of Next Dosing (AUC [0-tau]) of CAB LA Following Administration of CAB LA + RPV LA Q4W

  Blood samples were collected for PK analysis.

  Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)

• Area Under the Concentration Curve From 0 Hours to the Time of Next Dosing (AUC [0-tau]) of RPV LA Following Administration of CAB LA + RPV LA Q4W

  Blood samples were collected for PK analysis.

  Weeks -4 and -3, Pre-dose on Day 1 (Pre-Thigh Gluteal Injection); 2 Hours post-dose on Day 1, Week 1 post-dose, Pre-dose on Week 4 (First Thigh Injection); 2 Hours post-dose on Week 12, Week 13 post-dose and Pre-dose on Week 16 (Last Thigh Injection)

Secondary Outcomes (22)

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

  Up to Week 16

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

  Up to Week 16

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

  Up to Week 16

• Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (Copies/mL) Using the Food and Drug (FDA) Snapshot Algorithm-Thigh Injection Phase

  Baseline (Day 1) and at Weeks 4, 8, 12, 16

• Percentage of Participants With Plasma HIV RNA Greater Than or Equal to (>=)50 Copies/mL Over Time as Per the FDA Snapshot Algorithm- Thigh Injection Phase

  Baseline (Day 1) and at Weeks 4, 8, 12, 16

Study Arms (2)

Participants receiving CAB LA 400 milligrams (mg) and RPV LA 600 mg

EXPERIMENTAL

Participants will receive an Intramuscular (IM) injection of CAB LA 400 mg on one lateral thigh and RPV LA 600 mg into the opposite lateral thigh on Day 1 in every 4 weeks (Q4W) for a total of 16 weeks during Thigh injection phase. Participants will then return to the clinic 4 weeks later to receive their first IM gluteal injection (at Week 16) of CAB LA 400 mg and RPV LA 600 mg during the Return to Gluteal Injection Phase. The subsequent gluteal injection will occur at Week 20.

Drug: Cabotegravir Injectable Suspension; Drug: Rilpivirine Injectable Suspension

Participants receiving CAB LA 600 mg and RPV LA 900 mg

EXPERIMENTAL

Participants will receive an IM injection of CAB LA 600 mg on one lateral thigh and RPV LA 900 mg into the opposite lateral thigh on Day 1 in every 8 weeks (Q8W) for a total of 16 weeks during Thigh injection phase. Participants will then return to the clinic 8 weeks later receive their first IM gluteal injection (at Week 16) of CAB LA 600mg and RPV LA 900 mg during the Return to Gluteal Injection phase. The subsequent gluteal injection will occur at Week 24.

Drug: Cabotegravir Injectable Suspension; Drug: Rilpivirine Injectable Suspension

Interventions

Cabotegravir Injectable Suspension DRUG

CAB LA injectable suspension is a sterile white to slightly pink suspension containing 200 milligrams per milliliter (mg/mL) of GSK1265744 as free acid for administration by IM injection. CAB LA injectable suspension is to be stored at up to 30 degree Celsius and should not be frozen.

Participants receiving CAB LA 400 milligrams (mg) and RPV LA 600 mg; Participants receiving CAB LA 600 mg and RPV LA 900 mg

Rilpivirine Injectable Suspension DRUG

RPV LA injectable suspension is a sterile white suspension containing 300 mg/mL of RPV as the free base for administration by IM injection. RPV LA injectable suspension should be kept in the outer package and stored at 2-8 degree Celsius and should not be frozen. RPV LA should also be protected from light.

Participants receiving CAB LA 400 milligrams (mg) and RPV LA 600 mg; Participants receiving CAB LA 600 mg and RPV LA 900 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 sub-study specific informed consent.
• Eligible participants must have been on CAB LA + RPV LA regimen for a minimum of 152 weeks while on the ATLAS2-M study. Any disruptions in dosing during ATLAS2-M must be discussed with the Medical Monitor for a final determination of eligibility into the sub-study.
• Plasma HIV-1 RNA \<50 copies/mL at Sub-Study Screening.
• A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin \[hCG\] 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:
• i. Documented tubal ligation ii. Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion iii. Hysterectomy iv. 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, 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:

• Participants with more than 1 plasma HIV-1 RNA measurement \>=50 copies/mL to \<200 copies/mL (virologic blip) within 24 weeks prior to sub-study Screening visit.
• Any Suspected Virologic Failure (HIV-RNA greater than \[\>\]200 copies/mL as defined in during ATLAS-2M study.
• Participants planning to require oral bridging during participation in the ATLAS-2M sub-study.
• The participant has a tattoo or any dermatological condition overlying the thigh region 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.
• Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.
• Participants with moderate to severe hepatic impairment.
• Any pre-existing physical or mental condition (including substance use 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.
• Participants who, in the investigator's judgment, pose a significant suicide risk. Participant's recent history of suicidal behavior and/or suicidal ideation should be considered when evaluating for suicide risk.
• Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment).
• History of liver cirrhosis with or without hepatitis viral co-infection.
• Ongoing or clinically relevant pancreatitis.
• Clinically significant cardiovascular disease, as defined by history/evidence of congestive heart failure, symptomatic arrhythmia, angina/ischemia, coronary artery bypass grafting (CABG) surgery or percutaneous transluminal coronary angioplasty (PTCA) or any clinically significant cardiac disease.
• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (32)

GSK Investigational Site

Bakersfield, California, 93301, United States

Location

GSK Investigational Site

Fort Lauderdale, Florida, 33316, United States

Location

GSK Investigational Site

Ft. Pierce, Florida, 34982, United States

Location

GSK Investigational Site

Sarasota, Florida, 34237, United States

Location

GSK Investigational Site

Vero Beach, Florida, 32690, United States

Location

GSK Investigational Site

Macon, Georgia, 31201, United States

Location

GSK Investigational Site

Omaha, Nebraska, 68198, United States

Location

GSK Investigational Site

New York, New York, 10029, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15212, United States

Location

GSK Investigational Site

Lynchburg, Virginia, 24501, United States

Location

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, C1202ABB, Argentina

Location

GSK Investigational Site

Rosario, Santa Fe Province, S2000PBJ, Argentina

Location

GSK Investigational Site

Ottawa, Ontario, K1H 8L6, Canada

Location

GSK Investigational Site

Regina, Saskatchewan, S4P 0W5, Canada

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Berlin, 10787, Germany

Location

GSK Investigational Site

Hamburg, 20246, Germany

Location

GSK Investigational Site

Milan, Lombardy, 20157, Italy

Location

GSK Investigational Site

Badalona, 08916, Spain

Location

GSK Investigational Site

Barcelona, 08035, Spain

Location

GSK Investigational Site

Elche (Alicante), 03203, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28041, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Málaga, 29010, Spain

Location

GSK Investigational Site

Santiago de Compostela, 15706, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

Valencia, 46014, Spain

Location

GSK Investigational Site

Vigo, 36312, Spain

Location

GSK Investigational Site

Gothenburg, SE-416 85, Sweden

Location

GSK Investigational Site

Stockholm, SE-14186, Sweden

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

cabotegravir

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: ViiV Healthcare

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 9, 2023
• Study Start: October 28, 2021
• Primary Completion: August 23, 2022
• Study Completion: August 23, 2022
• Last Updated: September 18, 2023
• Results First Posted: September 18, 2023

Record last verified: 2023-08

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

SE (2); ES (11); DE (4); CA (2); AR (2); US (10); IT (1)