A Study to Evaluate the Effectiveness of Long-acting (LA) Cabotegravir (CAB) + Rilpivirine (RPV) LA When Given to Participants With Detectable HIV-1 (CROWN)

ViiV Healthcare

Status and phase: Not yet enrolling; Phase 3

Conditions: HIV Infections

Treatments: Drug: Oral ART; Drug: CAB LA + RPV LA

Study type: Interventional

Funder types: Industry

Identifiers

NCT06694805

2024-515070-28-00 (Other Identifier)

221611

Details and patient eligibility

About

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.

Enrollment: 324 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age

  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 5. Person of childbearing potential (POCBP) must have a negative serum or urine pregnancy test at screening and on Day 1.

• Informed Consent/Assent 6.Informed consent/Assent must be provided as follows:

  1. 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.
  2. 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

1. HIV-1 Subtype A6, if known from historical result.

2. Participants who are pregnant, breast/chest feeding or plan to become pregnant or breast/chest feed during the study.

3. 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).

4. 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.

5. History of liver cirrhosis with or without hepatitis viral co-infection.

6. Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.

7. Participants with HCV co-infection will be excluded entry into this study if they are currently receiving anti-HCV therapy at baseline (Day 1).

8. Participants determined by the investigator to have a high risk of seizures, including participants with an unstable or poorly controlled seizure disorder.

9. 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.

10. Participants who in the investigator's judgment, pose a significant suicidality risk. Participant's history of suicidal behaviour and/or suicidal ideation should be considered when evaluating for suicide risk.

11. Any pre-existing physical or mental condition 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.

    • Prior/Concomitant Therapy

12. Any previous use of CAB.

13. Current or anticipated need for chronic anti-coagulants.

14. Use of concomitant medications which are associated with Torsades de Pointes (TdP).

15. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.

16. Treatment with any of the following agents within 28 days of Screening:

    1. radiation therapy;
    2. cytotoxic chemotherapeutic agents;
    3. tuberculosis therapy with the exception of isoniazid;
    4. anti-coagulation agents, with the exception of the use of low dose acetylsalicylic acid (<=325mg);
    5. immunomodulators that alter immune responses such as chronic systemic corticosteroids, interleukins, or interferons.

17. Exposure to an experimental drug or experimental vaccine within either 28 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 the first dose of investigational medicinal product (IP).

18. Participants receiving any protocol-prohibited medication and who are unwilling or unable to switch to an alternate medication.

    • Prior/Concurrent Clinical Study Experience

19. Participant is currently participating in, or anticipates being selected for, any other interventional study.

    • Diagnostic assessments

20. Any evidence of viral drug resistance based on the presence of any major RAM to INSTIs or NNRTIs in the Screening result; or, if known, in any historical resistance test result.

21. 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.

22. Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities. A single repeat test is allowed during the Screening period to verify a result.

23. ALT >=5 times ULN or ALT >=3×ULN and bilirubin >=1.5×ULN (with >35% direct bilirubin).

24. eGFR of <30 mL/min/1.73 m2 via refitted, race-neutral CKD-EPIcr_R method (adult participants) or <50 mL/min/1.73 m2 using the Bedside Schwartz equation (adolescent participants).

25. Hemoglobin <9.0 g/dL.

26. Corrected QT interval (QTc >450 msec or QTc >480 msec for participants with bundle branch block, calculated using ECGs performed in triplicate).

    • Other exclusions

27. Unwilling to receive injections, or unable to receive gluteal injections.

28. The participant has gluteal implants or prosthesis; or a tattoo or other dermatological condition overlying the gluteus region which may interfere with interpretation of injection site reaction (ISRs).

29. The presence of at least 6 symptoms of alcohol or substance use disorder within the previous 12 months, using a diagnostic and statistical manual of mental disorders fifth edition (DSM-V) aligned screening checklist.

30. Adolescents who are wards of the state or government. To assess any potential impact on participant eligibility with regard to safety, the investigator must refer to the Investigator's brochure (IB) and supplements, approved product labels, and/or local prescribing information for detailed information regarding warnings, precautions, contraindications, AEs, drug interactions, and other significant data pertaining to the study drugs.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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324 participants in 2 patient groups

CAB LA + RPV LA Group

Experimental group

Description:

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

Treatment:

Drug: CAB LA + RPV LA

Oral ART Control Group

Active Comparator group

Description:

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

Treatment:

Drug: Oral ART