PH 3b, CAB + RPV in people with suboptimal response to oral ART (CROWN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Viiv Healthcare UK Limited

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

23 Dec 2024 → ongoing

Decision date (initial)

2025-09-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515070-28-00

ClinicalTrials.gov

NCT06694805

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Pharmacokinetic, Safety, Others

To demonstrate a superior viral suppression rate after 6 months of CAB LA + RPV LA, administered every 2 months, compared with oral ART in treatment experienced PWH with viremia

Secondary objectives 5

1. To compare time to viral suppression through 6 months of CAB LA + RPV LA, administered every 2 months vs. oral ART in treatment experienced PWH with viremia
2. To compare time to Treatment Related Discontinuation (=Failure) through 6 months of CAB LA + RPV LA administered every 2 months vs oral ART in treatment experienced PWH with viremia
3. To compare the rate of confirmed virologic failure after 6 months of CAB LA + RPV LA, administered every 2 months, compared with oral ART in treatment experienced PWH with viremia
4. To compare the incidence of treatment-emergent RAMs after 6 months of CAB LA + RPV LA, administered every 2 months, compared with oral ART in treatment experienced PWH with viremia
5. To determine the incidence of treatment-emergent RAMs after 12 and 24 months of CAB LA + RPV LA, administered every 2 months, in treatment experienced PWH with viremia

Conditions and MedDRA coding

HIV Infections

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Aged at least 12 years old and weighting at least 35 kg
2. Documented HIV-1 infection with plasma HIV-1 RNA >1,000 and <100,000 c/mL
3. Evidence of insufficient virologic response to participant's current oral ART regimen (defined as participant having an active prescription) within 18 months before 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)
4. Currently being treated with/prescribed an oral ART regimen and willing to continue taking an oral ART regimen until after their Month 6 viral load result is available.
5. Participant (if aged 18+) or a participant's parent/legal guardian is able to give signed informed consent. Where applicable an adolescent participant is able to assent to participate in the study.
6. Staff study participants are eligible to participate if they are responsible for/involved in adherence support for CAB + RPV LA, are able to agree to and have the time to participate in interviews and questionnaire completion, and have the cognitive ability to complete questionnaires and take part in an interview that may take up to 60 minutes.

Exclusion criteria 21

1. HIV-1 subtype A6
2. Participants who are pregnant, breast/chest feeding or plan to become pregnant or breast/chest feed during the study
3. Unstable liver disease or a history of liver cirrhosis with or without hepatitis viral co-infection.
4. Co-infection with Hepatitis B where they would not be able to receive appropriate therapy for their HBV co-infection or with Hepatitis C if they are currently receiving anti-HCV therapy at Day 1
5. Participants with severe hepatic impairment (Class C) as determined by Child-Pugh classification.
6. Participants with a high risk of seizures, including those with an unstable or poorly controlled seizure disorder.
7. High sensitivity to any of the study medications or their components or drugs of their class, or a history of drug or other allergy that contraindicates their participation.
8. Participants who pose a significant suicidality risk. History of suicidal behavior and/or suicidal ideation should be considered when assessing suicide risk.
9. Pre-existing physical or mental condition that may interfere with the participant's ability to comply with the dosing schedule and/or protocol assessments, or which may compromise participant safety.
10. Any previous use of CAB
11. Current or recent use of medications prohibited or defined as exclusionary in the protocol.
12. 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 study medication.
13. Current or anticipated participation in another interventional study.
14. Evidence of viral drug resistance to INSTIs or NNRTIs at Screening or in any historical resistance test result.
15. Has exclusionary safety laboratory test results at Screening
16. QTc >450 msec or >480 msec for participants with bundle branch block at Screening
17. Unwilling to receive injections or unable to receive gluteal injections.
18. Participant has gluteal implants or prosthesis; or a tattoo or other dermatological condition in the gluteus region which may interfere with interpretation of injection site reactions.
19. Evidence of alcohol or substance use disorder within the previous 12 months, as assessed by the Investigator using standard methods for their site, that would interfere with the participant's safety.
20. Adolescents who are wards of the state.
21. Staff study participants will be excluded if they are not involved in adherence support for viremic patients on CAB + RPV LA or if they are unwilling to be audio recorded during the interviews.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Virologic response (HIV 1 RNA <50 c/mL) using the Snapshot Algorithm at Month 6

Secondary endpoints 5

1. Time to virologic suppression (HIV-1 RNA <50 c/mL) from baseline (Day 1) through Month 6
2. Time to TRDF (PDVF or drug-related AE, intolerability of injections, protocol defined stopping criteria or lack of efficacy) from baseline (Day 1) through Month 6
3. Protocol-defined VF through Month 6
4. Occurrence of developing RAMs through Month 6
5. Occurrence of developing INSTI or NNRTI RAMs through Months 12 and 24

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Viiv Healthcare UK Limited

Sponsor organisation

Viiv Healthcare UK Limited

Address

980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Viiv Healthcare UK Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Viiv Healthcare UK Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 12

Locations

5 EU/EEA countries · 37 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 253 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications