A Phase I, Randomized, Placebo-Controlled Study of the Safety, Antiviral & Immunomodulatory Activity of Broadly Neutralizing Antibodies 3BNC117-LS-J and 10-1074-LS-J in Combination in ART-treated Adults in sub-Saharan Africa Living with HIV during a Monitored Analytical Treatment Interruption
Study Details
1. To evaluate the safety and tolerability of intravenous infusions of 3BNC117-LS-J and 10-1074- LS-J in virally suppressed adults with HIV in sub-Saharan Africa.
2. To evaluate the efficacy of the combination of 3BNC117-LS-J and 10-1074-LS-J versus placebo in preventing the return of sustained HIV-1 viremia (confirmed HIV-1 viral load >200 copies/mL) for 24 weeks after ART discontinuation in adults with HIV who have maintained viral suppression prior to the analytical treatment interruption (ATI) in sub-Saharan Africa.
A5416/HVTN 806/HPTN 108 (also referred to as A5416) is a Phase I, double-blind, randomized, placebo-controlled multi-step study designed to evaluate the effects of the combination of long-acting broadly neutralizing antibodies (bNAbs) 3BNC117-LS-J and 10-1074-LS-J compared to placebo in adult people/participants living with HIV (PWH) who discontinue antiretroviral therapy (ART) during a monitored analytical treatment interruption (ATI).
Individuals living with HIV, age ≥18 to ≤70 years, on stable ART who have a CD4+ count of ˃450 cells/μL, plasma viral load [VL] <50 copies/mL for at least 96 weeks prior to Step 1 entry, no history of receipt of any therapeutic HIV vaccine or HIV monoclonal antibody therapy.
48 participants will be enrolled into Step 1:
Arm A (3BNC117-LS-J + 10-1074-LS-J): 32 participants;
Arm B (placebo): 16 participants
Up to 96 weeks (24 weeks in Step 1 [ATI], then if they have not met ART restart criteria, 48 weeks (week 25 to 72) in Step 2 [extended ATI], followed by 24 weeks in Step 3 [follow-up on ART])
Participants will be randomized in a 2:1 ratio to receive either the study investigational product (Arm A) or placebo (Arm B) and will discontinue ART 2 days later.
Arm A: 32 participants will receive a single intravenous infusion of 3BNC117-LS-J (30 mg/kg) and a single intravenous infusion of 10-1074-LS-J (10 mg/kg).
Arm B: 16 participants will receive a single intravenous infusion of Placebo for 3BNC117-LS-J (0.9% Sodium Chloride Injection) and a single intravenous infusion of Placebo for 10-1074-LS-J (0.9% Sodium Chloride Injection).
1. To evaluate the safety and tolerability of intravenous infusions of 3BNC117-LS-J and 10-1074- LS-J in virally suppressed adults with HIV in sub-Saharan Africa.
2. To evaluate the efficacy of the combination of 3BNC117-LS-J and 10-1074-LS-J versus placebo in preventing the return of sustained HIV-1 viremia (confirmed HIV-1 viral load >200 copies/mL) for 24 weeks after ART discontinuation in adults with HIV who have maintained viral suppression prior to the analytical treatment interruption (ATI) in sub-Saharan Africa.
1. To evaluate the efficacy of the combination of 3BNC117-LS-J and 10-1074-LS-J versus placebo in maintaining plasma HIV-1 RNA levels <50 copies/mL for 24 weeks after ART discontinuation in people/participants living with HIV (PWH) who have maintained viral suppression prior to the ATI.
2. To evaluate the efficacy of the combination of 3BNC117-LS-J and 10-1074-LS-J in preventing the return of sustained HIV-1 viremia (confirmed HIV-1 viral load >200 copies/mL) while serum concentration of each bNAb remains ≥10 mcg/mL after ART discontinuation in PWH who have maintained viral suppression prior to the ATI.
3. To evaluate the efficacy of the combination of 3BNC117-LS-J and 10-1074-LS-J in preventing the return of sustained HIV-1 viremia (confirmed HIV-1 viral load >200 copies/mL) for 24 weeks after serum concentration of each bNAb declines to <10 mcg/mL after ART discontinuation in PWH who have maintained viral suppression prior to the ATI.
4. To evaluate the pharmacokinetic (PK) parameters of the combination of 3BNC117-LS-J and 10-1074-LS-J during ATI in PWH in sub-Saharan Africa.
5. To estimate the minimum effective concentrations of bNAbs required to maintain viral suppression.
6. To evaluate evidence of anti-drug antibodies (ADA) against 3BNC117-LS-J and/or 10-1074-LS-J in samples collected at selected time points throughout the study.
7. To evaluate the effects of the combination of 3BNC117-LS-J and 10-1074-LS-J on CD4+ T-cell count after ART discontinuation in adults with HIV who have maintained viral suppression prior to the ATI.