Post-Injectable Cabotegravir Antiretroviral Salvage Strategy Options Trial

NCT ID: NCT06485154

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-01
• Study Completion Date: 2026-08-31

Brief Summary

This is a single-arm, open-label, effectiveness study designed to evaluate the use of Tenofovir, Lamivudine, and Dolutegravir in people with newly diagnosed HIV-1 infection initiating first-line Antiretroviral Therapy with Cabotegravir-Long-acting Pre-Exposure Prophylaxis exposure in the preceding 12 months. Participants will be followed up for a period of 12 months from enrolment.

Detailed Description

Study participants are HIV-1 infected adult patients recruited. A target of 100 participants will be enrolled and started on Tenofovir, Lamivudine, and Dolutegravir at enrolment. Clinical assessments for these participants will be conducted throughout the study as per the Schedule of Events.

This will be a two-phase interventional study to identify the optimally safe and effective Antiretroviral Therapy regimen for individuals with newly detected Human Immunodeficiency Virus infection after Cabotegravir-Long-acting Pre-Exposure Prophylaxis exposure. In the Initial Phase, the investigator will demonstrate proof of principle for the use of standardized Antiretroviral Therapy regimens in combination with pre-treatment genotypic drug resistance testing to achieve virologic suppression in individuals with prior Cabotegravir-Long-acting Pre-Exposure Prophylaxis exposure and understand drug resistance patterns prior to Antiretroviral Therapy initiation. To do this, the investigator will use a single-arm, interventional design using Tenofovir, Lamivudine, and dolutegravir. This supports programmatic rollout, particularly in developing countries where baseline Human Immunodeficiency Virus genotyping is not performed prior to initiation of Antiretroviral Therapy. The over-arching goals of Phase I are to determine the feasibility of our study design to recruit people with detectable Human Immunodeficiency Virus after prior use of Cabotegravir-Long-acting Pre-Exposure Prophylaxis failure and to estimate virologic suppression rates with current first-line standard of care, Tenofovir, Lamivudine, and Dolutegravir therapy.

At the conclusion of the Initial Phase, data will be assessed to determine the need for and optimal design of a potential Second Phase (the details of which will not be described in this protocol). Should the investigator find sub-optimal virologic suppression rates on Tenofovir, Lamivudine, and Dolutegravir regimens in this trial, the investigator would then proceed to the Second Phase in which the investigator will compare Darunavir/Ritonavir based Antiretroviral Therapy with Tenofovir, Lamivudine, and Dolutegravir in an open-label randomized, non-inferiority clinical trial. The aim of the second phase will be to determine whether an alternative to the predominant first-line regimen in much of the world will be required to optimise virologic suppression for this population.

Conditions

HIV Prevention

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

TLD - Tenofovir Disoproxil Fumarate / Lamivudine / Dolutegravir

The IMP is defined as any investigational marketed product to be administered to a study participant according to the study protocol.

Participants will all receive TLD as detailed below. Treatment will be open-label, and drugs will be dispensed at intervals as specified in the Schedule of Events.

Investigational Product Tenofovir disoproxil fumarate / lamivudine / dolutegravir Dosage Formulation 300 mg / 300 mg / 50 mg fixed dose combination tablet Route of Administration Oral Dosing Instructions 1 tablet (300/300/50 mg TDF/3TC/DTG) daily

Group Type: EXPERIMENTAL

TLD - Tenofovir Disoproxil Fumarate / Lamivudine / Dolutegravir

Intervention Type: DRUG

Dolutegravir, lamivudine and tenofovir disoproxil fumarate tablets, a combination of dolutegravir (integrase strand transfer inhibitor \[INSTI\]), lamivudine, and tenofovir disoproxil fumarate (both nucleoside reverse transcriptase inhibitors), is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg

Interventions

TLD - Tenofovir Disoproxil Fumarate / Lamivudine / Dolutegravir

Dolutegravir, lamivudine and tenofovir disoproxil fumarate tablets, a combination of dolutegravir (integrase strand transfer inhibitor \[INSTI\]), lamivudine, and tenofovir disoproxil fumarate (both nucleoside reverse transcriptase inhibitors), is indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 35 kg

Intervention Type: DRUG

Other Intervention Names

Acriptega

Eligibility Criteria

Inclusion Criteria

1. Male or female.

2. Age ≥ 15 years, inclusive, at the time of signing the informed consent.

3. Body weight ≥ 35 kg.

4. Confirmed HIV-1 infection.

5. Exposure to at least one dose of CAB-LA PrEP in the past 12 months.

6. Consent to initiation of ART.

7. Estimated glomerular filtration rate (eGFR) > 50 min/mL

Exclusion Criteria

1. Any previous exposure to DTG.

2. Concurrent or recent (within the preceding 3 months) participation in another interventional clinical trial with a compound likely to interfere with any of the investigational medicinal products.

3. Known hypersensitivity or specific contraindications to the use of any of the active drugs in the treatment arms or similar compounds.

4. Is receiving or has received the following agents within 28 days prior to screening, and cannot discontinue their use for the duration of the study:

1. tuberculosis therapy (i.e., rifampicin, rifapentine, rifabutin), with the exception of isoniazid (INH) prevention therapy;

2. anti-convulsants (e.g., carbamazepine, oxcarbazepine, phenobarbital, phenytoin);

3. herbal products (e.g., St John's Wort).

5. Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the safety of the volunteer or the objectives of the study or impair their ability to comply with the dosing schedule and/or protocol evaluations. The Investigator should make this determination in consideration of the volunteer's medical history.

6. Participant is judged by the Investigator to be at significant risk of failing to comply with the provisions of the protocol as to cause harm to self or seriously interfere with the validity of the study results. This including inability or an unwillingness to be followed up for the study period.

• Minimum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bill and Melinda Gates Foundation

OTHER

Sponsor Role: collaborator

University of Witwatersrand, South Africa

OTHER

Sponsor Role: lead

Responsible Party

Professor Francois Venter

Executive Director: Ezintsha

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

FRANCOIS WD VENTER, PhD

Role: STUDY_DIRECTOR

Ezintsha, a division of Wits Health Consortium

Locations

Ezintsha, a division of Wits Health Consortium

Johannesburg, Gauteng, South Africa

Africa Health Research Institute (AHRI)

Durban, KwaZulu-Natal, South Africa

Desmond Tutu Health Foundation

Cape Town, Western Cape, South Africa

Countries

South Africa

Other Identifiers

EZ-BB-036

Identifier Type: -

Identifier Source: org_study_id