Long-Acting Cabotegravir Plus VRC-HIVMAB075-00-AB (VRC07-523LS) for Viral Suppression in Adults Living With HIV-1
- Conditions
- HIV Infections
- Interventions
- Drug: Oral Cabotegravir (CAB)Drug: Nucleoside Reverse Transcriptase Inhibitors (NRTIs)Drug: Long-Acting Injectable Cabotegravir (CAB LA)Biological: VRC07-523LSDrug: Standard of Care (SOC) Oral ART
- Registration Number
- NCT03739996
- Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and antiviral activity 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 will assess the safety, tolerability, pharmacokinetics, and antiviral activity 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.
The study will be conducted in three steps. At Step 1 entry, all participants will discontinue their current antiretroviral therapy (ART) regimen except for nucleoside reverse transcriptase inhibitors (NRTIs), and initiate oral CAB.
During Step 1, participants tolerating oral CAB plus their current two NRTIs, and displaying viral suppression (HIV-1 RNA \<50 copies/mL), will register to Step 2. At entry into Step 2, eligible participants will stop their oral CAB and NRTIs and will receive a VRC07-523LS infusion plus CAB LA injection. After entry in Step 2, participants will receive CAB LA every 4 weeks through Week R2+44 plus VRC07-523LS every 8 weeks through Week R2+40.
At the last visit in Step 2 (Week R2+48), or at premature study treatment discontinuation, all participants who received any CAB LA or VRC07-523LS will enter Step 3 and switch to standard of care (SOC) oral ART for approximately 48 weeks.
Participants will attend a number of study visits throughout the study. Study visits may include a physical examination, clinical assessment, pregnancy testing, and blood and urine collection. Participants will remain in the study for up to 101 weeks, including approximately 5 weeks in Step 1, 48 weeks in Step 2, followed by 48 weeks in Step 3.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 75
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CAB LA + VRC07-523LS Standard of Care (SOC) Oral ART Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for 5 weeks. Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week R2+44. VRC07-523LS (40 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 8 weeks through Week R2+40. Step 3: SOC oral ART regimen for approximately 48 weeks. CAB LA + VRC07-523LS Oral Cabotegravir (CAB) Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for 5 weeks. Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week R2+44. VRC07-523LS (40 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 8 weeks through Week R2+40. Step 3: SOC oral ART regimen for approximately 48 weeks. CAB LA + VRC07-523LS Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for 5 weeks. Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week R2+44. VRC07-523LS (40 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 8 weeks through Week R2+40. Step 3: SOC oral ART regimen for approximately 48 weeks. CAB LA + VRC07-523LS VRC07-523LS Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for 5 weeks. Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week R2+44. VRC07-523LS (40 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 8 weeks through Week R2+40. Step 3: SOC oral ART regimen for approximately 48 weeks. CAB LA + VRC07-523LS Long-Acting Injectable Cabotegravir (CAB LA) Step 1: CAB administered orally as one 30 mg tablet once daily, plus two NRTIs, for 5 weeks. Step 2: CAB LA loading dose (600 mg) administered as one IM injection at Step 2 entry study visit, and maintenance dose (400 mg), starting at 4 weeks after CAB LA loading dose, and then every 4 weeks through Week R2+44. VRC07-523LS (40 mg/kg) administered as an IV infusion starting at Step 2 entry and then every 8 weeks through Week R2+40. Step 3: SOC oral ART regimen for approximately 48 weeks.
- Primary Outcome Measures
Name Time Method Frequency of either 1) the occurrence of a Grade 3 or higher adverse event (AE); or 2) premature study treatment discontinuation due to an AE (regardless of grade) Measured through Week R3+48 of Step 3 Both of which are possibly, probably, or definitely related (as judged by the core team) to the CAB LA plus VRC07-523LS combination.
Number of participants who experience virologic failure Measured through Week R2+44 of Step 2 Defined as confirmed HIV-1 RNA greater than or equal to 200 copies/mL
- Secondary Outcome Measures
Name Time Method Frequency of viral resistance of breakthrough isolates Measured through Week R2+44 of Step 2 Based on laboratory evaluations
Trough levels of the concentration of CAB LA Measured through Week R2+48 of Step 2 Based on PK sampling
Number of participants who experience virologic failure Measured through Week R2+44 of Step 2 Defined by the U.S. Food and Drug Administration (FDA) snapshot algorithm
Frequency of either 1) virologic failure (confirmed HIV-1 RNA greater than or equal to 200 copies/mL); or 2) premature discontinuation of the CAB LA plus VRC07-523LS combination Measured through Week R2+44 of Step 2 Based on laboratory evaluations
Number of participants with confirmed HIV-1 RNA greater than or equal to 50 copies/mL Measured through Week R2+24 of Step 2 Based on laboratory evaluations
Number of participants with either 1) confirmed HIV-1 RNA greater than or equal to 50 copies/mL; or 2) premature discontinuation of the CAB LA plus VRC07-523LS combination Measured through Week R2+44 of Step 2 Based on laboratory evaluations
Frequency of anti-idiotype antibodies against VRC07-523LS in samples collected from representative time points throughout the study Measured through Week R2+48 of Step 2 Based on laboratory evaluations
Frequency of either 1) the occurrence of a Grade 3 or higher AE; or 2) premature oral CAB discontinuation due to an AE (regardless of grade) Measured through Week 5 of Step 1 Both of which are possibly, probably, or definitely related (as judged by the core team) to oral CAB.
Number of participants who prematurely discontinue oral CAB or the CAB LA plus VRC07-523LS combination Measured through Week R2+44 of Step 2 Based on self report
Frequency of the occurrence of a Grade 3 or higher AE that is possibly, probably, or definitely related (as judged by the core team) to oral CAB or the CAB LA plus VRC07-523LS combination Measured through Week R3+48 of Step 3 Frequency of the occurrence of a Grade 3 or higher AE that is possibly, probably, or definitely related (as judged by the core team) to oral CAB or the CAB LA plus VRC07-523LS combination
Trough levels of the concentration of VRC07-523LS Measured through Week R2+48 of Step 2 Based on PK sampling
Trial Locations
- Locations (19)
Johns Hopkins University CRS
🇺🇸Baltimore, Maryland, United States
Puerto Rico AIDS Clinical Trials Unit CRS
🇵🇷San Juan, Puerto Rico
UCSD Antiviral Research Center CRS
🇺🇸San Diego, California, United States
University of Washington AIDS CRS
🇺🇸Seattle, Washington, United States
University of Colorado Hospital CRS
🇺🇸Aurora, Colorado, United States
Weill Cornell Chelsea CRS
🇺🇸New York, New York, United States
Penn Therapeutics, CRS
🇺🇸Philadelphia, Pennsylvania, United States
Ohio State University CRS
🇺🇸Columbus, Ohio, United States
Chapel Hill CRS
🇺🇸Chapel Hill, North Carolina, United States
Cincinnati Clinical Research Site
🇺🇸Cincinnati, Ohio, United States
Alabama CRS
🇺🇸Birmingham, Alabama, United States
Washington University Therapeutics (WT) CRS
🇺🇸Saint Louis, Missouri, United States
Northwestern University CRS
🇺🇸Chicago, Illinois, United States
Ucsf Hiv/Aids Crs
🇺🇸San Francisco, California, United States
Rush University CRS
🇺🇸Chicago, Illinois, United States
Columbia P&S CRS
🇺🇸New York, New York, United States
New Jersey Medical School Clinical Research Center CRS
🇺🇸Newark, New Jersey, United States
Weill Cornell Uptown CRS
🇺🇸New York, New York, United States
University of Rochester Adult HIV Therapeutic Strategies Network CRS
🇺🇸Rochester, New York, United States