RECRUITING

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

Conditions

HIV Infections HIV Infection Cabotegravir Rilpivirine Long-acting Efficacy Safety Durability

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2024-12-02

Study Completion:2027-12-08

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06694805

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * 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.	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. 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. 19. Participant is currently participating in, or anticipates being selected for, any other interventional study. 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). 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.

Inclusion Criteria

Exclusion 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.
* 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.

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

Contacts and Locations

Study Contact

US GSK Clinical Trials Call Center

CONTACT

877-379-3718

GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466

GSKClinicalSupportHD@gsk.com

Study Locations (Sites)

GSK Investigational Site

Newark, Delaware, 19711

United States

GSK Investigational Site

West Palm Beach, Florida, 33401

United States

GSK Investigational Site

Decatur, Georgia, 30033

United States

GSK Investigational Site

Macon, Georgia, 31201

United States

GSK Investigational Site

Chicago, Illinois, 60611

United States

GSK Investigational Site

Chicago, Illinois, 60613

United States

GSK Investigational Site

Kansas City, Missouri, 64111

United States

GSK Investigational Site

Saint Louis, Missouri, 63110

United States

GSK Investigational Site

Newark, New Jersey, 07102

United States

GSK Investigational Site

Dallas, Texas, 75246

United States

Collaborators and Investigators

Sponsor: ViiV Healthcare

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-02

Study Completion Date2027-12-08

Study Record Updates

Study Start Date2024-12-02

Study Completion Date2027-12-08

Terms related to this study

Keywords Provided by Researchers

HIV Infection
Cabotegravir
Rilpivirine
Long-acting
Efficacy
Safety
Durability

Additional Relevant MeSH Terms

HIV Infections