A Study to Evaluate Efficacy and Safety of Cabotegravir (CAB) Long Acting (LA) Plus (+) Rilpivirine (RPV) LA Versus BIKTARVY® (BIK) in Participants With Human Immunodeficiency Virus (HIV)-1 Who Are Virologically Suppressed

• Status: Active, not recruiting
• Trial end date: 2023-06-26
• Target enrollment: 0
• Participant gender: All

Summary

Human immunodeficiency virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) is a worldwide epidemic that continues to grow significantly causing new infections and related deaths per year. Chronic HIV infection in adults continues to be characterized by increased development and transmission of resistant virus and issues associated with long-term toxicity of antiretroviral therapy (ART). The current paradigm in the treatment of HIV involves life-long therapy with multiple antiretrovirals (ARVs). This dependency on medical therapy requires a need for continuous improvement on the durability, tolerability and convenience of all antiretroviral classes. This is a Phase IIIb, randomized, open-label, active-controlled, multicenter, parallel-group, non-inferiority study (SOLAR: Switch Onto Long Acting Regimen). It is designed to assess the antiviral activity and safety of a two-drug regimen of CAB LA + RPV LA administered every 2 months (Q2M) compared with maintenance of BIK. Approximately 654 adult HIV-1 infected participants who are on the stable ARV regimen BIK will be randomized in a 2:1 ratio to either be switched to the CAB LA + RPV LA regimen or continue BIK through 12 months. The study will continue with an Extension Phase after Month 12 Oral Lead-In (OLI) and BIK/Month 11 Direct to Injection (D2I).

BIKTARVY is a registered trademark of Gilead Sciences.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ViiV Healthcare
• Collaborator: Janssen, LP
• Treatments: Cabotegravir; Rilpivirine

Criteria

Inclusion Criteria:

• Participants aged 18 years or older (or >=19 where required by local regulatory agencies), at the time of signing the informed consent.

• A female participant is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotropin (hCG) test at screen and a negative urine hCG test at Randomization), 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:

1. Documented tubal ligation.

2. Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion.

3. Hysterectomy.

4. 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 enrolment.

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.

• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Eligible participants or their legal guardians (and next of kin when locally required), must sign a written Informed Consent Form before any protocol-specified assessments are conducted. Enrolment of participants who are unable to provide direct informed consent is optional and will be based on local legal/regulatory requirements and site feasibility to conduct protocol procedures.

• Participants enrolled in France must be affiliated to, or a beneficiary of, a social security category.

• Must be on the uninterrupted current regimen of BIK for at least 6 months prior to Screening with an undetectable HIV-1 viral load for at least 6 months prior to Screening. Only a single prior Integrase inhibitor (INI) regimen is allowed if BIK is a second line regimen >= 6 months prior to screening. Any prior change in regimen, defined as a change of a single drug or multiple drugs simultaneously, must have occurred due to tolerability/safety, access to medications, or convenience/simplification, and must not have been done for treatment failure (HIV-1 RNA >=400 c/mL).

Only a single prior INI regimen is permitted with the following limited exceptions

• A change from Tenofovir disoproxil fumarate (TDF) to TAF will not be considered a regimen change.

• Historical perinatal use of Nucleoside reverse transcriptase inhibitor (NRTI) when given in addition to an ongoing Highly active antiretroviral therapy (HAART) will not be considered a change in ART regimen.

• The past use of ARVs in the context of Post Exposure Prophylaxis (PEP) or Pre-Exposure Prophylaxis (PrEP) while the participant was HIV negative will be allowed. Such cases will be evaluated on a case by case basis and may require documentation of HIV negative serology during time of PEP or PrEP.

• A change in dosing scheme of the same drug from twice daily to once daily will not be considered a change in ART regimen if data support similar exposures and efficacy.

• A change in formulation from multiple class regimens to single treatment regimens (of the same medications) would not be considered a change in ART regimen.

• Documented evidence of plasma HIV-1 RNA measurements <50 c/mL in the 6 months prior to Screening.

• Plasma HIV-1 RNA <50 c/mL at Screening.

Exclusion Criteria:

• Within 6 months prior to Screening, any plasma HIV-1 RNA measurement >=50 c/mL.

• Within the 6 to 12-month window prior to Screening, any plasma HIV-1 RNA measurement greater than (>)200 c/mL, or 2 or more plasma HIV-1 RNA measurements >=50 c/mL.

• History of prior treatment failure to any Department of Health and Human Services (DHHS) recommended ART regimen.

• History of drug holiday >1 month for any reason prior to Screening visit, except where all ART was stopped due to tolerability and/or safety concerns.

• Any change to a second line regimen, defined as change of a single drug or multiple drugs simultaneously, due to virologic failure to therapy (defined as a confirmed plasma HIV 1 RNA measurement >=200 c/mL after initial suppression to <50 c/mL while on first line HIV therapy regimen).

• Participants who are currently participating in or anticipate being selected for any other interventional study.

• 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 CD4+ counts <200 cells/mL 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 enrolment 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 enrolment.

• All participants will be screened for syphilis.

• Participants with untreated secondary (late latent) or tertiary syphilis infection, defined as a positive rapid plasma reagin (RPR) and a positive treponemal test without clear documentation of treatment, are excluded.

• Participants with a false positive RPR (with negative treponemal test) or serofast RPR result (persistence of a reactive nontreponemal syphilis test despite history of adequate therapy and no evidence of re-exposure) may enroll after consultation with the Medical Monitor.

• Participants with primary syphilis or early latent secondary syphilis (acquired within the preceding year) who have a positive RPR test and have not been treated may be treated during the screening period and if completion of antibiotic treatment occurs during the screening period, may be allowed entry after consultation with the Medical Monitor. If antibiotic treatment cannot be completed before the screening window ends, participants may be rescreened once following completion of antibiotic therapy for primary or early latent secondary syphilis.

• 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.

• The participant has a tattoo, gluteal implant/enhancements 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 DNA as follows:

1. Participants positive for HBsAg are excluded.

2. Participants negative for anti-HBs but positive for anti-HBc (negative HBsAg status), whether negative or positive for HBV DNA, are excluded.

• Asymptomatic individuals with chronic hepatitis C virus (HCV) infection will not be excluded, however Investigators must carefully assess if therapy specific for HCV infection is required; participants who require or qualify for immediate HCV treatment are excluded for those co-infected participants who post entry into SOLAR decide treatment for HCV infection is warranted or desired either by the participant or by the treating physician.

Participants with HCV co-infection will be allowed entry into this study if:

1. Liver enzymes meet entry criteria

2. HCV Disease has undergone appropriate work-up, and is not advanced, and will not require treatment prior to the Month 14 visit. Additional information (where available) on participants with HCV co-infection at screening should include results from any liver biopsy, Fibroscan, ultrasound, or other fibrosis evaluation, history of cirrhosis or other decompensated liver disease, prior treatment, and timing/plan for HCV treatment.

3. In the event that recent biopsy or imaging data is not available or inconclusive, the fibrosis (Fib)-4 score will be used to verify eligibility

i. Fib-4 score >3.25 is exclusionary ii. Fib-4 scores 1.45-3.25 requires Medical Monitor consultation

Fibrosis 4 Score Formula:

d. Age x aspartate aminotransferase (AST)/ Platelets x (square [Alanine aminotransferase {ALT}]).

• 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, or decompensated cirrhosis [for example {e.g.} ascites, encephalopathy, or variceal bleeding]), 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 pharmacokinetic (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 (less than or equal to [<=]325 mg) or hereditary coagulation and platelet disorders such as hemophilia or Von Willebrand Disease.

• Corrected QT interval (QTc [Bazett]) >450 milliseconds (msec) or QTc (Bazett) >480 msec for participants with bundle branch block.

• Known or suspected active Coronavirus Disease-2019 (COVID-19) infection or has had contact with an individual with known COVID-19, within 14 days of study enrolment.

• Known or suspected presence of resistance mutations as defined by the International Antiviral Society-United Sates of America (IAS-USA) resistance guidelines to the individual components of BIK (BIC, FTC, TAF), RPV, and CAB by any historical resistance test result.

• 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 <30mL/minute per 1.73 meter square (m^2) via Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) Method.

• ALT >=3 times upper limit of normal (ULN).

• Exposure to an experimental drug 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:

• radiation therapy;

• cytotoxic chemotherapeutic agents;

• tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid/INH);

• anti-coagulation agents;

• 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.

• Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 within 28 days of study Day 1. Treatment with acyclovir/valacyclovir is permitted.

• 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.