NCT05769569

Safety and Efficacy of Neutralizing Antibodies and Vaccination for Induction of HIV Remission

Safety and Efficacy of Broadly Neutralizing Antibodies Followed by Innate Immune Stimulation and Therapeutic Vaccination for the Induction of HIV Remission

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Henry M. Jackson Foundation for the Advancement of Military Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This is a phase I, randomized, open-label trial to investigate the safety of VRC07-523LS, PGDM1400LS and N-803 in combination with Ad26.Mos4.HIV, MVA-Bavarian Nordic (BN)-HIV and A244d11gp120/ALFQ vaccination, and the impact on time to sustained viral rebound of ≥1000 copies/mL for 4 consecutive weeks during analytic treatment interruption (ATI) in people living with human immunodeficiency virus-1 (HIV-1, PLWH) who initiated antiretroviral therapy (ART) during acute HIV-1 infection (AHI).

Detailed description

This is a phase 1 study. The study duration is approximately 134 weeks. The primary objectives are: 1. To evaluate the safety of VRC07-523LS, PGDM1400LS and N-803 in combination with Ad26.Mos4.HIV, MVA-BN-HIV and A244d11 gp120/ALFQ vaccination in PLWH who initiated ART during AHI. 2. To evaluate the impact of VRC07-523LS, PGDM1400LS and N-803 in combination with Ad26.Mos4.HIV, MVA-BN-HIV and A244d11 gp120/ALFQ vaccination on time to sustained viral rebound to ≥1000 copies/mL for 4 consecutive weeks AND has not declined by \>0.2 log10 from the previous measurement during ATI.

Conditions

• HIV-1-infection

Interventions

Type	Name	Description
BIOLOGICAL	VRC07-523LS	VRC07-523LS is a recombinant human immunoglobulin G1 (IgG1) broadly neutralizing monoclonal antibody (bNAb) directed against the HIV-1 CD4 binding site. Intravenous infusion of 10 mg/kg VRC07-523LS will be administered on Week 0.
BIOLOGICAL	PGDM1400LS	PGDM1400LS is a recombinant human IgG1 bNAb targeted against the HIV-1 V2 apex epitope region. Intravenous infusion of 20 mg/kg PGDM1400LS will be administered on Week 0.
BIOLOGICAL	N-803	N-803 is a recombinant human superagonist interleukin-15 (IL-15) complex. N-803 at 6 ug/kg will be administered via subcutaneous injection to the trunk on Weeks 1, 4, 7, 39, 42 and 45.
BIOLOGICAL	Ad26.Mos4.HIV	Ad26.Mos4.HIV is a tetravalent vaccine comprising Ad26.Mos1.Env, Ad26.Mos2S.Env, Ad26.Mos1.Gag-Pol, and Ad26.Mos2.Gag-Pol. Ad26.Mos4.HIV at 5x1010 viral particles (per 0.5 mL dose) will be administered through intramuscular injection in the quadriceps muscle at Week 11.
BIOLOGICAL	MVA-BN-HIV	MVA-BN-HIV is a single vector recombinant Modified Vaccinia Ankara - Bavarian Nordic (MVA-BN®) expressing Mos1.Env, Mos2S.Env, Mos1.Gag-Pol, and Mos2.Gag-Pol. MVA-BN-HIV at 2x108 infectious unit (per 0.5mL dose) will be administered through intramuscular injection in the quadriceps muscle at Week 35.
BIOLOGICAL	A244d11 gp120	A244d11 gp120, consists of the gp120 envelope glycoprotein HIV-1 subtype CRF\_01AE A244 derived from the CM244 CRF\_01AE strain, with an 11 amino N-terminal deletion. It is a modification of the A244 rgp120 immunogen from the AIDSVAX®B/E vaccine. A244d11 gp120 at 300 ug will be administered as an intramuscular injection in the quadriceps muscle at week 11 and week 35.
BIOLOGICAL	ALFQ	ALFQ (Army Liposome Formulation, ALF) is a liposomal adjuvant containing a synthetic monophosphoryl lipid A (MPLA, 3D-PHAD®) with the addition of QS-21. ALFQ at 200 ug will be administered as an intramuscular injection in the quadriceps muscle at week 11 and week 35.
COMBINATION_PRODUCT	Antiretroviral Therapy (ART)	This study will enroll PLWH aged 18-50 years who initiated ART during Fiebig I-V AHI and are virologically suppressed (HIV RNA \<50 copies/ml for ≥48 weeks) on uninterrupted ART, who meet study inclusion criteria in Bangkok, Thailand.

Timeline

• Start date: 2023-09-01
• Primary completion: 2025-07-01
• Completion: 2025-07-01
• First posted: 2023-03-15
• Last updated: 2024-05-03

Locations

2 sites across 1 country: Thailand

Regulatory

• FDA-regulated drug study