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

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).

Conditions

• HIV-1-infection

Interventions

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.

Sponsors & Collaborators

• US Military HIV Research Program

  collaborator NETWORK

• Janssen Vaccines & Prevention B.V.

  collaborator INDUSTRY

• Henry M. Jackson Foundation for the Advancement of Military Medicine

  lead OTHER

Principal Investigators

• Donn Colby, M.D., M.P.H. · US Military HIV Research Program

• Kiat Ruxrungtham, MD · King Chulalongkorn Memorial Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

50 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2023-09-01

Primary Completion

2025-07-01

Completion

2025-07-01

FDA Drug

Yes

Countries

• Thailand

Study Locations