A Phase 3b, Open Label, Randomized, standard-of Care Control Arm, Multicenter, Superiority Study Evaluating the Efficacy, Safety, and Tolerability of Injectable CAB LA + RPV LA in Viremic Participants Living With HIV-1 (CROWN)

ViiV Healthcare90 sites in 5 countries332 target enrollmentDecember 2, 2024

InterventionsCAB LA + RPV LA Oral ART

DrugsCAB LA + RPV LA Oral ART

Overview

Phase: Phase 3
Intervention: CAB LA + RPV LA
Conditions: Not specified
Sponsor: ViiV Healthcare
Enrollment: 332
Locations: 90
Primary Endpoint: Number of participants with virologic suppression after the CAB LA + RPV LA treatment compared to oral ART
Status: Recruiting
Last Updated: 12 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study will assess how effective, safe, and long-lasting a long-acting antiretroviral therapy (ART) using CAB LA + RPV LA is for people with HIV who still have detectable virus levels despite being on oral ART. The study will also consider feedback from patients on their experience with this treatment.

Registry

clinicaltrials.gov

Start Date

December 2, 2024

End Date

July 19, 2028

Last Updated

12 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

ViiV Healthcare

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•1\. Aged \>=12 years and \>=35 kg (at the time of obtaining informed consent).
•Type of Participant and Disease Characteristics 2.HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA VL.
•3.Plasma HIV-1 RNA \>1 000 c/mL and greater than (\<) 100 000 c/mL at Screening. 4.Evidence of insufficient virologic response to participant's current oral ART regimen within 18 months prior to study entry according to at least 1 of the following criteria: i.\<1 log10 decrease in HIV-1 RNA or HIV-1 RNA \>200 c/mL at 2 time points at least 4 weeks apart in individuals who have been prescribed oral ART for at least 3 consecutive months.
•ii. Documented lapse in current oral ART regimen usage expected to result in HIV-1 viremia (defined as at least a 30-day consecutive period of non-use of oral ART) iii. Documented need for change from oral ART regimen that investigator attributes as primary reason for insufficient virologic response (e.g., safety findings and/or limited tolerability, clinically relevant DDIs).
•Currently being treated with an oral ART regimen specific regimen to be recorded at Screening, and willing to continue taking that regimen until approximately 1 week after the Month 6 visit.
•Pregnancy, Sex and Contraceptive/Barrier Requirements
•Person of childbearing potential (POCBP) must have a negative serum or urine pregnancy test at screening and on Day
•Informed Consent/Assent 6.Informed consent/Assent must be provided as follows:
•Adult participants (\>=18 years old) must be capable of giving signed informed consent as described in the full study protocol, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and stated in the full study protocol.
•For adolescent participants (12 to \<18 years of age at screening), the parent(s) or legal guardian must be capable of giving signed informed consent.

Exclusion Criteria

•Medical Conditions
•HIV-1 Subtype A6, if known from historical result.
•Participants who are pregnant, breast/chest feeding or plan to become pregnant or breast/chest feed during the study.
•Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones).
•Individuals with both HIV and Hepatitis B virus (HBV) will be excluded from participating in studies where they would not be able to receive appropriate therapy for their HBV co-infection and therefore may be at risk of hepatitis B flare. Exclusion will be determined by evidence of HBV infection based on the results of testing at Screening for HBsAg, HBcAb, HBsAb and HBV.
•History of liver cirrhosis with or without hepatitis viral co-infection.
•Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
•Participants with HCV co-infection will be excluded entry into this study if they are currently receiving anti-HCV therapy at baseline (Day 1).
•Participants determined by the investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder.
•History of sensitivity to any of the study medications or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

Arms & Interventions

CAB LA + RPV LA Group

Participants receive initial injections at Day 1 and Month 1, followed by maintenance injections every 2 months for up to 24 months.

Intervention: CAB LA + RPV LA

Oral ART Control Group

Participants continue to take their current oral ART for 6 months, including a final dose at their first injection visit.

Intervention: Oral ART

Outcomes

Primary Outcomes

Number of participants with virologic suppression after the CAB LA + RPV LA treatment compared to oral ART

Time Frame: At Month 6

A virologic suppression is defined by HIV-1 RNA less than (\<) 50 copies (c)/mL.

Secondary Outcomes

Time to virologic suppression(From Baseline (Day 1) up to Month 6)
Time to treatment related discontinuation (=Failure) (TRDF)(From Baseline (Day 1) up to Month 6)
Number of participants with confirmed protocol-defined virologic failure (VF)(From Baseline (Day 1) up to Month 6)
Number of participants with treatment-emergent resistance-associated mutations (RAMs)(From Baseline (Day 1) up to Month 6)
Number of participants with treatment-emergent RAMs(Up to Month 12 and Month 24)
Number of participants with serious adverse events (SAEs)(Up to Month 6, Month 12, and Month 24)
Number of deaths(Up to Month 6, Month 12, and Month 24)
Number of participants with Grade 2 to 5 drug-related adverse events (AEs)(Up to Month 6, Month 12, and Month 24)
Number of AEs leading to discontinuation(Up to Month 6, Month 12, and Month 24)