SEARCH CAB LA Dynamic Choice HIV Prevention Study Extension

NCT05549726 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: SEARCH CAB LA ExtensionU01AI150510
• Study Type: interventional
• Target: 984
• Locations: 2 countries
• Sites: 2

Brief Summary

The overall purpose of this SEARCH CAB-LA (Cabotegravir Injectable Suspension) randomized extension study is to determine if adding the option of CAB-LA as a prevention choice using a person-centered dynamic choice HIV (human immunodeficiency virus) prevention model, with option to switch products over time, compared to the standard of care: 1) increases prevention coverage; 2) reduces HIV incident infection; and 3) increases prevention coverage during periods of self-assessed risk of HIV infection, in three settings in rural Uganda and Kenya. In addition, this study will describe implementation of a person-centered model for dynamic choice HIV prevention including CAB-LA, using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) evaluation framework among persons randomized to the intervention arm.

Conditions

HIV

Keywords

Cabotegravir Injectable Suspension; PrEP; HIV Treatment and Prevention; Community Health

Outcome Measures

Primary Outcomes (1)

• Biomedical Prevention Covered Time

  Number of days participant taking biomedical prevention divided by number of days participant biomedical prevention use measured. Biomedical prevention includes PrEP tenofovir disoproxil fumarate/lamivudine (TDF/3TC) or cabotegravir long-acting injectable (CAB-LA) and PEP

  48 weeks

Secondary Outcomes (3)

• HIV Incident Infection

  48 weeks

• HIV Incident Infection

  96 weeks

• Biomedical Prevention During Periods of Self Assessed HIV Risk

  96 weeks

Study Arms (2)

Dynamic choice prevention (including CAB LA)

EXPERIMENTAL

The Dynamic Choice Delivery Model includes integrated PrEP and PEP services at outpatient clinics, antenatal clinics, and via VHT workers in community households. CAB-LA will be integrated into the dynamic choice delivery model as an additional biomedical prevention option in a patient-centered delivery model based on the precede framework.

Drug: Cabotegravir Injectable Suspension; Other: Dynamic Choice Delivery Model

Standard of Care

ACTIVE COMPARATOR

The standard of care for PEP or PrEP differs according to each country's guidelines.

Other: Standard of Care

Interventions

Cabotegravir Injectable Suspension DRUG

CAB-LA will be one of the options for the Dynamic Choice Delivery intervention arm. CAB-LA will be a choice for at-risk adults and adolescents weighing at least 35 kg for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 infection. Single-dose vial containing 600 mg/3 mL (200 mg/mL) of cabotegravir is a white to light pink, free-flowing, extended-release injectable suspension. CAB-LA administration will occur at health facilities.

Dynamic choice prevention (including CAB LA)

Dynamic Choice Delivery Model OTHER

The Dynamic Choice Delivery Model includes integrated PrEP (including CAB-LA) and PEP services at outpatient clinics, antenatal clinics, and via VHT workers in community households. The procedures for each trial include PrEP/PEP counseling and services, choice of service location, HIV testing options, option for longer PrEP refills, provision of a clinical officer's or nurse's mobile telephone number for immediate PEP starts any day of the week, assessment of PrEP/PEP barriers and personalized actions, psychologic supports for traumatic experiences, and offer of concurrent, additional health or prevention related services.

Dynamic choice prevention (including CAB LA)

Standard of Care OTHER

The standard of care differs according to country but does not routinely offer PEP or PrEP to clients seeking services, does not offer choice of service location, HIV testing option or access to medical provider mobile phone number.

Standard of Care

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Enrollment in a SEARCH Sapphire Dynamic prevention study (NCT04810650)
• HIV negative at start of extension
• Residing in study region
• Not pregnant or breastfeeding at time of initial CAB-LA injection
• Participant weighs at least 35kg

You may not qualify if:

• Participant has Hepatitis B or chronic Hepatitis C Diagnosis
• Participant has ALT \>=5x ULN
• Participant has clinical history of liver cirrhosis or current clinical evidence of cirrhosis
• Previous hypersensitivity reaction to cabotegravir
• Receiving the following co-administered drugs for which significant decreases in cabotegravir plasma concentrations may occur due to uridine diphosphate glucuronosyltransferase:
• i. Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin ii. Antimycobacterials: Rifampin, rifapentine
• Participants with a current or anticipated need for chronic systemic anticoagulation or a history of known or suspected bleeding disorder, including a history of prolonged bleeding, except for the use of anticoagulation for deep vein thrombosis (DVT) prophylaxis (e.g., postoperative DVT prophylaxis) or the use of low dose acetylsalicylic acid (≤325 mg).

Sponsors & Collaborators

• University of California, San Francisco: lead
• Infectious Diseases Research Collaboration, Uganda: collaborator
• Makerere University: collaborator
• Kenya Medical Research Institute: collaborator
• University of California, Berkeley: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator
• National Institute of Mental Health (NIMH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• ViiV Healthcare: collaborator
• University of Pittsburgh: collaborator

Study Sites (2)

GPRT / SEARCH Office

Kisumu, Kenya

Location

IDRC Southwest Uganda

Mbarara, Uganda

Location

Related Publications (1)

• Kamya MR, Balzer LB, Ayieko J, Kabami J, Kakande E, Chamie G, Sutter N, Sunday H, Litunya J, Schwab J, Schrom J, Bacon M, Koss CA, Rinehart AR, Petersen M, Havlir DV; SEARCH Consortium. Dynamic choice HIV prevention with cabotegravir long-acting injectable in rural Uganda and Kenya: a randomised trial extension. Lancet HIV. 2024 Nov;11(11):e736-e745. doi: 10.1016/S2352-3018(24)00235-2. Epub 2024 Oct 9.

  PMID: 39395424 DERIVED

MeSH Terms

Interventions

cabotegravir; Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Limitations and Caveats

Participants maintained their original randomization group; so balance at extension start wasn't guaranteed. Sensitivity analyses adjusted for baseline differences, but unmeasured differences may remain. Self-reported pill ingestion (PrEP/PEP) may have recall bias; CABLA injections were logged. HIV incidence differences validate intervention impact.We relied on self-reported risk without specific classifications and evaluated a combination intervention,complicating effect attribution.

Results Point of Contact

• Title: Tamara Clark
• Organization: UCSF

tamara.clark@ucsf.edu

415-517-3444

Study Officials

• Diane Havlir, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Moses Kamya, MBChB, PhD

  Makerere University

  PRINCIPAL INVESTIGATOR

• Maya Petersen, MD, PhD

  University of California, Berkeley

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants initially randomized to the Dynamic Choice Prevention delivery model will be given the option to use CAB-LA as part of the dynamic choice prevention delivery package. Participants initially randomized to standard of care will continue to receive standard of care.

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: September 22, 2022
• Study Start: January 2, 2023
• Primary Completion: December 18, 2023
• Study Completion: January 30, 2025
• Last Updated: February 20, 2025
• Results First Posted: January 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

KE (1); UG (1)