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

NCT ID: NCT05896761

Last Updated: 2023-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 118 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-28
• Study Completion Date: 2022-08-23

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)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Cabotegravir Injectable Suspension

Intervention Type: 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.

Rilpivirine Injectable Suspension

Intervention Type: 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 600 mg and RPV LA 900 mg

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.

Group Type: EXPERIMENTAL

Cabotegravir Injectable Suspension

Intervention Type: 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.

Rilpivirine Injectable Suspension

Intervention Type: 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.

Interventions

Cabotegravir Injectable Suspension

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.

Intervention Type: DRUG

Rilpivirine Injectable Suspension

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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:

1. 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.

2. 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.

Exclusion Criteria

• 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.
• Any evidence of a current Center for Disease Control and Prevention (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy, and Cluster of Differentiation 4 positive (CD4+) counts <200 cells per microliter are not exclusionary.
• 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.
• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the participant prior to randomization.
• 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.
• History or presence of allergy or intolerance to the study drugs or their components or drugs of their class. In addition, if heparin is used during PK sampling, participants with a history of sensitivity to heparin or heparin-induced thrombocytopenia must not be enrolled.
• Current or anticipated need for chronic anti-coagulation with the exception of the use of low dose acetylsalicylic acid lesser than or equal to (<=)325 mg or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.
• Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening phase to verify a result.
• Any acute laboratory abnormality at Screening, which, in the opinion of the investigator, would preclude the participant's participation in the study of an investigational compound.
• Participant has estimated creatine clearance <50mL per minute per 1.73 square meter via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method.
• Alanine aminotransferase (ALT) >=3 × upper limit of normal (ULN) at Screening.
• Exposure to an experimental drug (with the exception of those in the ATLAS-2M study including CAB, CAB LA, and RPV, RPV LA) or experimental vaccine within either 30 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to Day 1 of this study.
• Treatment with any of the following agents within 28 days of Screening:

i. radiation therapy; ii. cytotoxic chemotherapeutic agents; iii. tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid [INH]); iv. anti-coagulation agents; v. Immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons

• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.
• Use of medications which are associated with Torsade de Pointes.
• Participants receiving any prohibited medication and who are unwilling or unable to switch to an alternate medication.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Bakersfield, California, United States

GSK Investigational Site

Fort Lauderdale, Florida, United States

GSK Investigational Site

Ft. Pierce, Florida, United States

GSK Investigational Site

Sarasota, Florida, United States

GSK Investigational Site

Vero Beach, Florida, United States

GSK Investigational Site

Macon, Georgia, United States

GSK Investigational Site

Omaha, Nebraska, United States

GSK Investigational Site

New York, New York, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Lynchburg, Virginia, United States

GSK Investigational Site

Ciudad de Buenos Aires, Buenos Aires, Argentina

GSK Investigational Site

Rosario, Santa Fe Province, Argentina

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Regina, Saskatchewan, Canada

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Hanover, Lower Saxony, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Milan, Lombardy, Italy

GSK Investigational Site

Badalona, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Elche (Alicante), , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Málaga, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

GSK Investigational Site

Seville, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Vigo, , Spain

GSK Investigational Site

Gothenburg, , Sweden

GSK Investigational Site

Stockholm, , Sweden

Countries

United States; Argentina; Canada; Germany; Italy; Spain; Sweden

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

207966-001

Identifier Type: -

Identifier Source: org_study_id