Extension of SEARCH SAPPHIRE Dynamic Choice Prevention Study

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05549726
• Collaborator: Infectious Diseases Research Collaboration, Uganda (Other), Makerere University (Other), Kenya Medical Research Institute (Other), University of California, Berkeley (Other), National Institute of Allergy and Infectious Diseases (NIAID) (NIH), National Institute on Alcohol Abuse and Alcoholism (NIAAA) (NIH), National Institute of Mental Health (NIMH) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH), ViiV Healthcare (Industry), University of Pittsburgh (Other)
• Enrollment: 600
• Locations: 2
• Arms: 2
• Anticipated Duration (Months): 23.6
• Patients Per Site: 300
• Patients Per Site Per Month: 12.7

Study Details

Study Description

Brief Summary

The overall purpose of this SEARCH SAPPHIRE CAB-LA extension study is to 1) Determine if adding the option of Cabotegravir Injectable Suspension (CAB-LA) as a prevention choice using a patient-centered HIV prevention delivery model increases prevention coverage compared to the standard-of-care in three ongoing randomized trials of Dynamic Choice Prevention in rural Uganda and Kenya; and, 2) Conduct a hybrid implementation study (Primary Objective Clinical and Secondary Objective Implementation) focusing on initial implementation of a patient-centered model for CAB-LA using the RE-AIM evaluation framework among persons randomized to the intervention arms.

Condition or Disease	Intervention/Treatment	Phase
HIV	Drug: Cabotegravir Injectable Suspension; Other: Dynamic Choice Delivery Model; Other: Standard of Care	Phase 4

Detailed Description

The SEARCH SAPPHIRE CAB-LA extension study a 48 week extension of three ongoing randomized trials studying a patient-centered "Dynamic Choice Prevention" (DCP) implementation strategy for delivering existing evidence-based biomedical prevention interventions vs. standard of care (SOC). The Dynamic prevention model offers participants choices on prevention modality on an ongoing basis: oral PrEP, or oral PEP, and the option to switch between products. The trials are being conducted in 3 settings: antenatal (ANC) clinics, the outpatient department (primary care clinics), and in rural community settings in Western Kenya and Uganda. All clinic and village health team staff (i.e., Clinical Officers, nurses, coordinators, health workers) are trained and equipped for HIV prevention care in the clinical setting, appropriate to their role. In the CAB-LA extension, participants in the intervention and control arms are reconsented and remain in their initial randomized arm. Persons in the intervention arms who remain HIV negative will be offered CAB-LA as an additional biomedical prevention option, if eligible. CAB-LA will be delivered at health clinics. The primary 48 week endpoint for this extension is proportion of time covered by a biomedical prevention product.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 600 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 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.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.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Multisectoral Strategy to Address Persistent Drivers of the HIV Epidemic in East Africa: Extension of SEARCH SAPPHIRE Dynamic Choice Prevention Study
• Anticipated Study Start Date: Oct 15, 2022
• Anticipated Primary Completion Date: Oct 1, 2024
• Anticipated Study Completion Date: Oct 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dynamic choice prevention (including CAB LA) 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; 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.; Other: Dynamic Choice Delivery Model; 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.
Active Comparator: Standard of Care The standard of care for PEP or PrEP differs according to each country's guidelines.	Other: Standard of Care; 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.

Outcome Measures

Primary Outcome Measures

1. Biomedical prevention covered time [48 weeks]

   Number of weeks participant taking biomedical prevention divided by number of weeks participant biomedical prevention use measured. Biomedical prevention includes PrEP (TDF/3TC or CAB-LA) and PEP

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Inclusion criteria for the Extension include:

1. Enrollment in a SEARCH Sapphire Dynamic prevention study (NCT04810650)

2. HIV negative at start of extension

3. Residing in study region

Additional inclusion criteria to access CAB-LA as a prevention option

1. Not pregnant or breastfeeding at time of initial CAB-LA injection

2. Participant weighs at least 35kg

Exclusion Criteria:

Exclusion criteria to access CAB-LA as a prevention option:

1. Participant has Hepatitis B or chronic Hepatitis C Diagnosis

2. Participant has ALT >=5x ULN

3. Participant has clinical history of liver cirrhosis or current clinical evidence of cirrhosis

4. Previous hypersensitivity reaction to cabotegravir

5. Receiving the following co-administered drugs for which significant decreases in cabotegravir plasma concentrations may occur due to uridine diphosphate glucuronosyltransferase:

1. Anticonvulsants: Carbamazepine, oxcarbazepine, phenobarbital, phenytoin ii. Antimycobacterials: Rifampin, rifapentine

1. 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GPRT / SEARCH Office	Kisumu		Kenya
2	IDRC Southwest Uganda	Mbarara		Uganda

Sponsors and Collaborators

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

Investigators

• Principal Investigator: 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT05549726
• Other Study ID Numbers: SEARCH SAPPHIRE DCP Extension; U01AI150510
• First Posted: Sep 22, 2022
• Last Update Posted: Sep 22, 2022
• Last Verified: Sep 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by University of California, San Francisco: Cabotegravir Injectable Suspension; PrEP; HIV Treatment and Prevention; Community Health; Youth and Adolescents
• Additional relevant MeSH terms: Cabotegravir

Study Results

No Results Posted as of Sep 22, 2022