Long-term Follow-up of Long-acting Cabotegravir (CAB LA) for PrEP (Pre-exposure Prophylaxis) in Participants at Risk of Acquiring HIV (Human Immunodeficiency Virus)

Study Overview
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Brief Summary
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The purpose of this study is long-term evaluation of long-acting injectable cabotegravir (CAB LA) for HIV pre-exposure prophylaxis (PrEP) in eligible participants who have completed DAIDS (Division of AIDS) sponsored studies HPTN 083 and HPTN 084 and associated sub-studies. Participants will continue receiving CAB LA and be followed for new HIV diagnosis, SAEs (serious adverse events), Grade 3 and Grade 4 ISRs (injection site reactions), and AEs (adverse events) leading to withdrawal.

Official Title
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A Phase IIIB, Long-Term Follow-Up of CAB LA for Participants in HPTN 083 and HPTN 084 CAB PrEP Studies at Risk of HIV Acquisition

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: CAB LA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be currently enrolled and ongoing in one of the following studies: HPTN 083 HPTN 084 HPTN 083 and HPTN 084 adolescent and pregnancy sub-studies Participants who have permanently withdrawn from prior CAB PrEP studies cannot enroll into this study. Evidence of continued benefit (HIV negative and at risk) from CAB LA during participation in the parent study/sub-study. Participants must have a nonreactive HIV test at Screening (rapid test, antigen/antibody test and HIV-1 RNA from the parent study/sub-study) and Day 1 (a rapid test and HIV Immunoassay [Antigen/Antibody test]). Males and Females: All participants who are engaging in sexual activity should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of acquiring HIV and other STIs. Females: Cisgender female participants who are of childbearing potential and who are engaging in sexual activity that could lead to pregnancy, must talk to the investigator about recommended contraception options. Contraception will be optional in this study. Condoms are recommended in addition, because their appropriate use is the only contraception method effective for preventing HIV-1 transmission. Pregnant participants from the HPTN 084 study are eligible to enroll into this study if they meet all eligibility criteria. Exclusion Criteria: Concurrent conditions/medical history (includes liver function): Participants who are currently enrolled in the eligible studies on the TDF/FTC arm are not eligible to enroll into this study. Participants receiving short-term oral TDF/FTC bridging may be enrolled following consultation with the Medical Monitor. Previous permanent discontinuation from IP in the parent study/sub-study. Known ALT >5 x ULN or ALT>3 x ULN and bilirubin >1.5 x ULN (with >35% direct bilirubin). Participants with known hepatitis B infection at any time prior to entry (as evidence by a positive Hepatitis B virus surface antigen positive and/or quantifiable Hepatitis B DNA PCR). 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), known biliary abnormalities (with the exception of hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator). Known history of cirrhosis with or without viral hepatitis co-infection. Participant is currently participating in or has participated in a study (other than the studies listed in Inclusion Criteria 1) with a compound or device that is not commercially available within 30 days of signing informed consent, unless permission from the Medical Monitor is granted. Presence of any history of allergy/sensitivity to any of the study drug. Inflammatory skin conditions that compromise the safety of IM injections, per the discretion of the investigator. Mild skin conditions may not be exclusionary at the discretion of the investigator or designee. Participant has a gluteal implant, tattoo or other dermatological condition overlying the buttock region which in the opinion of the investigator or designee may interfere with the injection or interpretation of ISRs. Coagulopathy (primary or iatrogenic) which would contraindicate IM injection. Concomitant medications: Use of any disallowed medications at time of screening. Anticipated need for HCV therapy with interferon or any drugs that have potential for adverse drug: drug interactions with study treatment throughout the entire study period. Relevant habits: Participant is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study. Any condition (including but not limited to alcohol and drug use) that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAB LA 600 mg (Q8W)<br>All enrolled participants have previously received CAB LA as part of the HPTN 083 and HPTN 084 parent studies or their sub-studies. Participants will continue receiving CAB LA 600 mg via gluteal intramuscular (IM) injection. | Drug: CAB LA<br>* Participants will receive CAB LA 600 mg via gluteal IM injection, once every 8 weeks (Q8W).<br>* Other names: CAB LA for PrEP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with new HIV infection |  | From Day 1 up to end of study (up to approximately [approx.] 3 years) | 
| Number of participants with new HIV infection by characteristic | Relevant characteristics of new HIV infections will be assessed, including presence of viral resistance to CAB. | From Day 1 up to end of study (up to approx. 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with serious adverse events (SAE) by severity | The severity scale is assessed as following: Grade 1 = mild symptoms causing no or minimal interference with usual social and functional activities with intervention not indicated. Grade 2 = moderate symptoms causing greater than minimal interference with usual social and functional activities with intervention indicated. Grade 3 = severe symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated. Grade 4 = potentially life-threatening symptoms causing inability to perform self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death. | From Day 1 up to end of study (up to approx. 3 years) | 
| Number of participants with Grade 3 and Grade 4 injection site reactions (ISRs) | ISRs may occur following intramuscular administration of CAB LA. Grade 3 refers to severe symptoms causing inability to perform usual social & functional activities with intervention or hospitalization indicated. Grade 4 refers to potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability or death. | From Day 1 up to end of study (up to approx. 3 years) | 
| Number of participants with any clinical or laboratory AE leading to discontinuation of CAB LA, by severity | Any clinical or laboratory AE that leads the participant to permanently discontinue CAB LA will be assessed. The severity scale is assessed as following: Grade 1 = mild symptoms causing no or minimal interference with usual social and functional activities with intervention not indicated. Grade 2 = moderate symptoms causing greater than minimal interference with usual social and functional activities with intervention indicated. Grade 3 = severe symptoms causing inability to perform usual social and functional activities with intervention or hospitalization indicated. Grade 4 = potentially life-threatening symptoms causing inability to perform self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death. | From Day 1 up to end of study (up to approx. 3 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Human Immunodeficiency Virus, CAB LA, Cabotegravir, Apretude, PrEP, HPTN 083, HPTN 084, DAIDS