NCT03739996

Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) for Viral Suppression in Adults Living With HIV-1

A Study of Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) to Maintain Viral Suppression in Adults Living With HIV-1

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 75 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study was to assess the safety, tolerability, antiviral activity, and pharmacokinetics of long-acting cabotegravir (CAB LA) plus the broadly neutralizing monoclonal antibody VRC-HIVMAB075-00-AB (VRC07-523LS), in adults living with HIV-1 with suppressed plasma viremia.

Detailed description

This study had a single, open-label arm and was conducted in three steps. At Step 1 entry, all participants discontinued their current antiretroviral therapy (ART) regimen, except for the 2 nucleoside reverse transcriptase inhibitors (NRTIs) and started oral CAB. Viral load monitoring occurred at entry, Week 4, and, conditionally, Week 5. During Step 1, participants who tolerated oral CAB plus their two NRTIs, maintained viral suppression, and met the other Step 2 eligibility requirements, registered for Step 2. Participants in Step 1 who were not eligible for Step 2 returned to their standard of care (SOC) regimen and were followed for an additional 4 weeks before being taken off the study. In Step 2, participants received CAB LA every 4 weeks through Step 2 Week 44 (12 injections) plus VRC07-523LS every 8 weeks through Step 2 Week 40 (6 infusions). Viral load monitoring occurred every 2 weeks through Week 8 and then every 4 weeks through Week 48. Any participant with a viral load of HIV-1 RNA ≥ 200 copies/mL had to attend an additional virologic failure confirmation visit within 14 days of the measured value. If virologic failure was confirmed (i.e., two consecutive HIV-1 RNA values ≥ 200 copies/mL), the participant transitioned to Step 3. After completion of Step 2 (Week 48), confirmed virologic failure, or premature treatment discontinuation, all participants who received any CAB LA or VRC07-523LS entered Step 3 and returned to SOC ART for 48 weeks, with visits at step entry and weeks 4, 12, 24, 36, and 48. The study's primary virology outcome pertains to Step 2 and only includes participants who started the CAB LA plus VRC07-523LS combination. The study's primary safety outcome pertains to Step 2 and Step 3 follow-up for participants who started the CAB LA plus VRC07-523LS combination. Study visits included physical examinations, clinical assessments, and blood and urine collection. The study opened to accrual in late December 2019. However, in March 2020 the study temporarily closed to screening and enrollment (including registration to Step 2) due to the COVID-19 pandemic. No participant had reached Step 2 of the study when the pause occurred. Participants in Step 1 were instructed to immediately stop the oral CAB plus 2 NRTI combination, resume their SOC regimen, and discontinue the study. The study reopened to screening and enrollment in September 2020. Analyses for this study only included participants who enrolled after the study reopened in September 2020. Participants previously enrolled were invited to rescreen and reenroll, if still eligible.

Conditions

• HIV Infections

Interventions

Type	Name	Description
DRUG	Oral Cabotegravir (CAB)	30 mg tablets administered orally
DRUG	Nucleoside Reverse Transcriptase Inhibitors (NRTIs)	NRTIs were not provided by the study. Participants obtained NRTIs outside of the study through routine care.
DRUG	Long-Acting Injectable Cabotegravir (CAB LA)	600 mg loading dose followed by 400 mg maintenance doses administered by intramuscular (IM) injection
BIOLOGICAL	VRC07-523LS	40 mg/kg administered as an intravenous (IV) infusion
DRUG	Standard of Care (SOC) ART	SOC ART was not provided by the study. Participants obtained SOC ART outside of the study through routine care.

Timeline

• Start date: 2019-12-31
• Primary completion: 2024-04-29
• Completion: 2024-04-29
• First posted: 2018-11-14
• Last updated: 2025-05-23
• Results posted: 2025-05-23

Locations

18 sites across 2 countries: United States, Puerto Rico

Regulatory

• FDA-regulated drug study