Safety, Tolerability, and Efficacy of IL-15 Superagonist (N-803) With and Without Combination Broadly Neutralizing Antibodies to Induce HIV-1 Control During Analytic Treatment Interruption
- Conditions
- HIV Infection
- Interventions
- Biological: N-803 (IL-15 Superagonist)Biological: VRC07-523LSBiological: 10-1074
- Registration Number
- NCT04340596
- Brief Summary
The purpose of this study is to evaluate the safety, tolerability, and efficacy of N-803, an IL-15 superagonist, with or without combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).
- Detailed Description
This study will evaluate the safety, tolerability, and efficacy of N-803, an IL-15 superagonist, with or without combination broadly neutralizing antibodies (bNAbs), to induce HIV-1 control during analytic treatment interruption (ATI).
Participants will be screened for eligibility and undergo leukapheresis, and a subset will also undergo optional rectal biopsy and/or lymph node fine needle aspirations (FNAs) (Step 1).
After pre-entry and determination of eligibility in Step 1, participants will be randomized before Step 2 entry to either the N-803 only arm (Arm A) or the N-803 with combination bNAbs arm (Arm B):
* Arm A will receive a dose of N-803, 6 mcg/kg, subcutaneously 1 week after Step 2 entry and then every 3 weeks for a total of eight doses (during the first 22 weeks).
* Arm B will receive the following (during the first 22 weeks):
* Combination bNAb at Step 2 entry with VRC07-523LS dosed at 20 mg/kg and 10-1074 dosed at 30 mg/kg, intravenously;
* A dose of N-803, 6 mcg/kg, subcutaneously 1 week after Step 2 entry and then every 3 weeks for a total of eight doses;
* A second dose of 10-1074 at week 9 of Step 2 dosed at 30 mg/kg, intravenously
After completing randomized treatment (Step 2), participants will interrupt antiretroviral therapy (ART) (Step 3) and will be followed closely to monitor for indications for reinitiation of ART (Step 4).
After Step 2 entry, most participants will be followed for approximately 100 weeks across the remaining three study steps (i.e., Steps 2, 3, and 4).
Step 1 will last up to 90 days, Step 2 will last approximately 52 weeks (study intervention), Step 3 will last up to 24 weeks (ATI), and Step 4 will last 24 weeks (ART restart).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 46
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: N-803 in combination with 10-1074 and VRC07-523LS N-803 (IL-15 Superagonist) Participants will receive N-803 in combination with 10-1074 and VRC07-523LS as follows: * At Step 2 entry: * VRC07-523LS 20 mg/kg * 10-1074 30 mg/kg * At Step 2, week 1: N-803 6 mcg/kg every 3 weeks for eight doses * At Step 2, week 9: 10-1074 30 mg/kg Arm B: N-803 in combination with 10-1074 and VRC07-523LS VRC07-523LS Participants will receive N-803 in combination with 10-1074 and VRC07-523LS as follows: * At Step 2 entry: * VRC07-523LS 20 mg/kg * 10-1074 30 mg/kg * At Step 2, week 1: N-803 6 mcg/kg every 3 weeks for eight doses * At Step 2, week 9: 10-1074 30 mg/kg Arm A: N-803 only N-803 (IL-15 Superagonist) Participants will receive N-803 6 mcg/kg 1 week after Step 2 entry and then every 3 weeks for a total of eight doses. Arm B: N-803 in combination with 10-1074 and VRC07-523LS 10-1074 Participants will receive N-803 in combination with 10-1074 and VRC07-523LS as follows: * At Step 2 entry: * VRC07-523LS 20 mg/kg * 10-1074 30 mg/kg * At Step 2, week 1: N-803 6 mcg/kg every 3 weeks for eight doses * At Step 2, week 9: 10-1074 30 mg/kg
- Primary Outcome Measures
Name Time Method Occurrence of a Grade ≥3 adverse event (AE) that is at least possibly related to N-803, as judged by the Clinical Management Committee (CMC) Step 2 week 1 to week 52 Proportion of participants requiring dose reduction From step 2 week 4 to step 2 week 22 Eight doses of N-803 are scheduled at distinct time points (Step 2 weeks 1, 4, 7, 10, 13, 16, 19 and 22). Proportion of participants requiring dose reduction is calculated as the number of participants who receive a reduced dose of N-803 at any of the 7 scheduled doses occurring after the first dose, divided by the total number of participants receiving N-803.
Number of N-803 doses completed From step 2 week 1 to step 2 week 22 Eight doses of N-803 are scheduled at the distinct time points listed in Time Frame. At each timepoint, dose completion status is recorded. Number of N-803 doses completed is the total number completed doses across all 8 timepoints.
Proportion of participants with plasma HIV-1 RNA <200 copies/mL 8 weeks after interruption of ART At step 3 week 8
- Secondary Outcome Measures
Name Time Method Cell-associated HIV-1 RNA At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32 Proportion of participants with antidrug antibodies At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46 Presence of anti-N803, anti-10-1074, and anti-VRC07-523LS antibodies
Occurrence of a Grade ≥2 AE that is at least possibly related to VRC07-523LS or 10-1074 Step 2 week 0 to week 52 PK parameters: AUC0-τ of 10-1074 At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46 Occurrence of a Grade ≥2 AE without regard to relationship to study treatment Study entry to participant's last study visit, at approx. study week 100 Occurrence of a Grade ≥2 AE that is at least possibly related to N-803, as judged by the CMC Step 2 week 1 to week 52 Measurement of HIV-1 reservoir (dQVOA) At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32 Proportion of participants with plasma HIV-1 RNA <200 copies/mL at 4, 12 and 24 weeks after interruption of ART in Step 3 At step 3 weeks 4, 12, and 24 PK parameters: AUC0-τ of VRC07-523LS At step 2 weeks 0, 1, 4, 7, 9, 10, 13, 16, 19, 22, 26, 32 and 46 Total HIV-1 DNA At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32 Measurement of plasma viremia by HIV-1 single copy assay At step 1 pre-entry evaluation and step 2 weeks 0, 1, 7, 13, 22 and 32 Measurement of intact proviral DNA At Step 2 weeks 0, 1, 7, 13, 19, 22, 26 and 32
Trial Locations
- Locations (15)
Alabama CRS (Site ID# 31788)
🇺🇸Birmingham, Alabama, United States
UCLA CARE Center CRS
🇺🇸Los Angeles, California, United States
UCSD Antiviral Research Center CRS (Site ID: 701)
🇺🇸San Diego, California, United States
University of California, San Fransisco HIV/AIDS CRS
🇺🇸San Francisco, California, United States
Whitman-Walker Institute, Inc. CRS (Site ID: 31791)
🇺🇸Washington, District of Columbia, United States
Northwestern University CRS
🇺🇸Chicago, Illinois, United States
Massachusetts General Hospital CRS (MGH CRS) (Site ID: 101)
🇺🇸Boston, Massachusetts, United States
Washington University Therapeutics (WT) CRS
🇺🇸Saint Louis, Missouri, United States
New Jersey Medical School Clinical Research Center CRS [Site ID: 31786]
🇺🇸Newark, New Jersey, United States
Columbia P&S CRS
🇺🇸New York, New York, United States
Weill Cornell Uptown CRS (Site ID: 7803)
🇺🇸New York, New York, United States
Chapel Hill CRS (Site ID: 3201)
🇺🇸Chapel Hill, North Carolina, United States
Case Clinical Research Site
🇺🇸Cleveland, Ohio, United States
Penn Therapeutics, CRS (Site ID: 6201)
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh CRS (Site ID# 1001)
🇺🇸Pittsburgh, Pennsylvania, United States