The Study of Immunization in People Living With HIV Undergoing an ATI for Elicitation of VRC01-lineage Antibodies

NCT06006546 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: HVTN 807
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 8

Brief Summary

This is a multicenter controlled interventional trial. This phase 1 trial is the first study to assess 426c.Mod.Core-C4b adjuvanted with 3M-052-AF + aluminum hydroxide suspension (Alum) in people living with HIV (PLWH).

Conditions

Chronic HIV Infection

Outcome Measures

Primary Outcomes (10)

• The number of participants local reactogenicity signs and symptoms

  14 days following each vaccination

• The number of participants systemic reactogenicity signs and symptoms

  14 days following each vaccination

• Number and description of serious adverse events (SAEs)

  adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult AEs

  12 months following any receipt of study product

• Number and description of medically attended adverse events (MAAEs)

  adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult AEs

  12 months following any receipt of study product

• Number and description of adverse events of special interest (AESIs)

  adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult AEs

  12 months following any receipt of study product

• Number and description of AEs leading to early participant withdrawal or permanent discontinuation and reason for withdrawal/discontinuation

  adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult AEs

  12 months following any receipt of study product

• Frequency of total Env-specific and CD4-bs-specific B cells, prior to ATI

  as assessed by flow cytometry at baseline and after each vaccination

  At baseline (week 0) and after each vaccination

• Frequency of VRC01-class BCR sequences of isolated CD4-bs B cells, prior to ATI

  , as assessed by B-cell sorting and BCR sequencing

  At baseline (week 0) and after each vaccination

• Frequency of Env-specific and CD4-bs-specific B cells

  as assessed by flow cytometry

  After week 16

• Frequency of VRC01-class BCR sequences of isolated CD4-bs B cells

  as assessed by B-cell sorting and BCR sequencing

  After week 16

Secondary Outcomes (3)

• Compare Env sequences during ATI in Group 1 participants that initiated the development of VRC01 antibodies and those that did not

  Study duration or 12 months following any receipt of study product

• Magnitude of Binding of selected recEnvs from Group 1 participants that initiated the development of VRC01-class antibodies to VRC01-class precursor and intermediate antibodies

  Study duration or 12 months following any receipt of study product

• Magnitude of Binding of selected recEnvs from Group 1 participants that initiated the development of VRC01-class antibodies to B cells expressing VRC01-class BCRs.

  Study duration or 12 months following any receipt of study product

Other Outcomes (7)

• Magntidue of binding and neutralizing activity of any VRC01-class antibodies isolated during the study

  Study duration or 12 months following any receipt of study product

• Frequency of occurrence of similarities s in viral sequences of Group 2 participants (if any viruses emerge on study) with Group 1 participants

  Study duration or 12 months following any receipt of study product

• Magnitude of participant and potential participant motivations, perceptions and tolerance for ATIs, for prolonged viremia, and for trial requirements (eg, ART switches, barrier protection for all sexual activity)

  Study duration or 12 months following any receipt of study product

Study Arms (2)

Group 1 (ATI)

EXPERIMENTAL

Group 1 will receive 2 doses of the vaccine at Week 0 and 12. Group 1 will transition to Schedule 2 at the Week 14 visit. The Schedule 2 "ATI with Monitoring" phase can last for 24 weeks OR until any antiretroviral therapy (ART) re-initiation criteria are met, OR the ATI can continue longer with the approval of the Protocol Safety Review Team (PSRT) and the participant's primary HIV healthcare provider. Group 1 will transition to Schedule 3, the "Follow-up on ART restart" phase that lasts until study week 64, regardless of the point where it begins.

Biological: 426c.Mod.Core-C4b; Other: Adjuvant 3M-052-AF+Alum

Group 2 (No ATI) Control

EXPERIMENTAL

Group 2 transitions from Schedule 1 into Schedule 4, "Follow-up on ART," at the Week 14 visit, and remains on Schedule 4 through study week 64.

Biological: 426c.Mod.Core-C4b; Other: Adjuvant 3M-052-AF+Alum

Interventions

426c.Mod.Core-C4b BIOLOGICAL

100 mcg and 300 mcg

Group 1 (ATI); Group 2 (No ATI) Control

Adjuvant 3M-052-AF+Alum OTHER

5 mcg

Group 1 (ATI); Group 2 (No ATI) Control

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to complete the informed consent process, including an Assessment of Understanding (AoU): Volunteer demonstrates an understanding of this study and completes a questionnaire prior to first vaccination with verbal demonstration of understanding of questionnaire items that were answered incorrectly.
• to 55 years old, inclusive, on day of enrollment.
• Confirmed HIV infection as documented by medical records or confirmatory HIV testing at screening.
• On suppressive ART for at least 48 weeks prior to screening. ART is defined as a combination therapy regimen including at least 1 integrase inhibitor and 1 nucleoside reverse transcriptase inhibitor (such as Dovato™) or 2 nucleoside reverse transcriptase inhibitors plus integrase inhibitors. Changes in ARVs for reasons other than virologic failure (eg, tolerability, simplification, different formulation, drug-drug interaction profile) are allowed within 48 weeks prior to screening and up until 6 weeks prior to screening. A fully active alternative ARV regimen is available, in the opinion of the Investigator, in the event of discontinuation of the current ARV regimen with development of resistance.
• Plasma HIV RNA \< 50 copies/mL (or lower limit of quantitation \[LLOQ\]) for at least 48 weeks prior to enrollment. NOTE: At least one viral load measurement within 48 weeks prior to the screening visit and another viral load from the screening prior to enrollment visit must be available for review. Two "blips" (ie, plasma HIV-1 RNA \> LLOQ and \< 400 copies/mL) are allowed if each blip is preceded and followed by values \< LLOQ and if the blip(s) occur(s) more than 24 weeks prior to enrollment.
• CD4+ cell count \> 450 cells/mm3 and CD4+ cell % ≥ 15% obtained within 40 days prior to enrollment.
• Available for clinic follow-up through the last clinic visit, willing to undergo leukapheresis, and willing to be contacted 12 months after the last study-product administration.
• Agrees not to enroll in another study of an investigational agent during participation in the trial. If a potential participant is already enrolled in another clinical trial, approvals from the other trial sponsor and the HVTN 807 PSRT are required prior to enrollment into HVTN 807.
• In good general health according to the clinical judgment of the site investigator.
• Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgement of the site investigator.
• Total serum calcium of ≥ 8.5 mg/dL.
• Hemoglobin (Hgb):
• ≥ 10.0 g/dL for volunteers who were assigned female sex at birth (AFAB)
• ≥ 11.0 g/dL for cisgender volunteers who were assigned male sex at birth (AMAB) and for transgender men who have been on hormone therapy for more than 6 consecutive months
• ≥ 11.0 g/dL for transgender women who have been on hormone therapy for more than 6 consecutive months

You may not qualify if:

• Current receipt of ART other than nucleoside reverse transcriptase inhibitor and integrase inhibitor.
• Receipt of long-acting ART within 3 months of enrollment.
• Documented history of resistance to any components of the current ARV regimen.
• Known resistance to 1 or more drugs in 2 or more ARV drug classes. NOTE: M184V/I is an exception and should not be considered when assessing this criterion. Prior HIV resistance testing is not required.
• ART initiation during acute HIV-1 infection (defined as within 1 year of HIV-1 acquisition, if known).
• History of an HIV-associated malignancy (including Kaposi's sarcoma), and any type of lymphoma or virus-associated cancers.
• History of HIV-associated neurocognitive disease or progressive multifocal leukoencephalopathy.
• Hepatitis B or C infection as indicated by the presence of Hepatitis B surface antigen (HBsAg), hepatitis C antibody without documented history of prior treatment and clearance, or hepatitis C virus RNA (HCV-RNA) in blood.
• Diagnosis of cirrhosis.
• Current untreated or incompletely treated active TB disease or untreated latent TB infection. NOTE: Individuals who are on treatment for latent TB with at least 4 weeks of treatment completed are not excluded.
• Volunteer who is breastfeeding or pregnant.
• Body mass index (BMI) ≥ 40. Enrollment of individuals with BMI ≥ 40, whom the site investigator assesses are in good health, may be considered by PSRT approval.
• History of or current clinical atherosclerotic cardiovascular disease (ASCVD), as defined by 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, including a previous diagnosis of any of the following:
• Acute myocardial infarction
• Acute coronary syndromes

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (8)

Birmingham

Birmingham, Alabama, 35294-2170, United States

Location

Atlanta- Ponce

Atlanta, Georgia, 30303, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS (Site #31440)

Decatur, Georgia, 30030, United States

Location

BIDMC

Boston, Massachusetts, 02215, United States

Location

Columbia P&S CRS Site#30329

New York, New York, 10032, United States

Location

University of Pittsburg

Pittsburgh, Pennsylvania, 15213, United States

Location

Seattle Vaccine and Prevention CRS (Site # 30331)

Seattle, Washington, 98104, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Interventions

Adjuvants, Pharmaceutic

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: August 23, 2023
• Study Start: January 3, 2024
• Primary Completion (Estimated): October 27, 2026
• Study Completion (Estimated): October 27, 2026
• Last Updated: January 14, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)