Safety and Immunogenicity of HIV-1 Vaccines C62-M4 or C1C62-M3M4 in Persons With HIV-1 Suppressed on ART

NCT05604209 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: 22-00945U01AI131310IGHID 12107
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

This is a double blind, randomized, placebo-controlled, parallel design study in which 18 in participants with HIV (PWH) on suppressive antiretroviral therapy will be randomly assigned to receive vaccination with C62 followed by M4 (C62-M4), C62 and C1 followed by M4 and M3 (C1C62-M3M4), or placebo. The purpose of this study is to find out:

• If it is safe for people to receive intramuscular (IM) vaccination with C62-M4 or C1C62-M3M4
• If giving participants these vaccine doses will improve their immune system response to help the body get rid of HIV in the cells

Conditions

HIV Vaccine; HIV-1-infection

Keywords

Vaccination; Immunogenicity; HIV-1; HIV vaccine; HIV; MVA; ChAdOx1; T-cell vaccine; Therapeutic T-cell vaccine

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With a Grade 3 or Higher Treatment-Related Adverse Event (AE)

  The DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017 was used to measure safety where Grade 1 is defined as mild, Grade 2 is defined as moderate, Grade 3 is defined as severe, and Grade 4 is defined as potentially life-threatening. Treatment-Related AEs were assessments that were considered related to study product as possible, probable, or definite as defined in the protocol. Confidence intervals around percentages were estimated using the Clopper-Pearson exact method.

  First day of study treatment through 28 days following last vaccination, an average of 2 months

Secondary Outcomes (6)

• Percent of Participants With a Grade 1 or Higher Treatment-Related Adverse Event (AE)

  First day of study treatment through day 196 (20 weeks following second vaccination), an average of 7 months

• Median Fold-change in Magnitude of T-cell Response to HIV-1 Mosaic-1 Immunogen

  Baseline to day 35

• Median Fold-change in Magnitude of T-cell Response to HIV-1 Mosaic-2 Immunogen

  Baseline to day 35

• Median Fold-change in Magnitude of T-cell Response to HIV-1 Mosaic-1 Immunogen

  Baseline to day 42

• Median Fold-change in Magnitude of T-cell Response to HIV-1 Mosaic-2 Immunogen

  Baseline to day 42

Study Arms (3)

C62-M4

EXPERIMENTAL

ChAdOx1.HIVconsv62 (C62) vaccine administered at Day 0, followed by MVA.tHIVconsv4 (M4) vaccine administered at Day 28

Biological: ChAdOx1.HIVconsv62; Biological: MVA.tHIVconsv4

C1C62-M3M4

EXPERIMENTAL

ChAdOx1.tHIVconsv1 (C1) and ChAdOx1.HIVconsv62 (C62) vaccines administered at Day 0, followed by MVA.tHIVconsv3 (M3) and MVA.tHIVconsv4 (M4) vaccines administered at Day 28

Biological: ChAdOx1.HIVconsv62; Biological: ChAdOx1.tHIVconsv1; Biological: MVA.tHIVconsv4; Biological: MVA.tHIVconsv3

Placebo

PLACEBO COMPARATOR

Placebo administered on Day 0 and Day 28

Other: Placebo

Interventions

ChAdOx1.HIVconsv62 BIOLOGICAL

Administered intramuscularly (IM) at Day 0

C1C62-M3M4; C62-M4

ChAdOx1.tHIVconsv1 BIOLOGICAL

Administered intramuscularly (IM) at Day 0

C1C62-M3M4

MVA.tHIVconsv4 BIOLOGICAL

Administered intramuscularly (IM) at Day 28

C1C62-M3M4; C62-M4

MVA.tHIVconsv3 BIOLOGICAL

Administered intramuscularly (IM) at Day 28

C1C62-M3M4

Placebo OTHER

Administered at intramuscularly (IM) Day 0 and Day 28

Also known as: Normal saline, Sodium chloride

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV infection documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral assay.
• A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
• Note: The term "licensed" refers to a US FDA-approved kit, which is required for all IND studies. World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment.
• Ages = 18 to = 70 years old
• Able and willing to give written informed consent.
• Able and willing to provide adequate locator information.
• Able and willing to comply with all study requirements through D196 Week 28.
• Continuous antiretroviral therapy (ART) prior to screening, defined as not missing more than 14 total days and never more than 7 consecutive days in the last 3 months prior to screening.
• No change in any ART medication in the 30 days prior to screening.
• Permitted ART regimens include:
• At least 3 ART agents (not counting ritonavir or cobicistat as one of the agents if less than a 200 mg total daily dose). One of the agents must include an integrase inhibitor, NNRTI (Non-Nucleoside Reverse Transcriptase Inhibitors), or a boosted-PI (protease inhibitor).
• Two (2) ART agents in which one of the agents is either a boosted protease inhibitor or an integrase inhibitor.
• Note: Other potent fully suppressive antiretroviral combinations will be considered on a case-by-case basis. Note: Changes in drug formulation or dose are allowed (e g, tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF), ritonavir to cobicistat or separate ART agent dosing to fixed-dose combination), but none within 30 days prior to screening.
• Note: Prior changes in, or elimination of, medications for easier dosing schedule, intolerance, toxicity, an improved side effect profile or within a drug class are permitted if an alternative suppressive regimen was maintained, but not within 30 days prior to screening.
• Ability and willingness of participant to continue ART throughout the study.

You may not qualify if:

• Women of childbearing age/potential who are breast feeding, pregnant, or planning pregnancy from enrollment to 4 months after the last vaccination at D28, D196.
• Untreated syphilis infection defined as a positive rapid plasma reagin (RPR) without clear documentation of treatment. Note: Potential participants may rescreen with documentation of adequate treatment. Participants reporting symptoms consistent with syphilis infection between the screening visit and the vaccination visit should be assessed to determine the need for repeat testing prior to vaccination.
• Current treatment for HCV or HCV treatment within 6 months prior to enrollment.
• HIV RNA =150 copies/mL in the 6 months prior to screening.
• Received any infusion blood product or hematopoetic growth factors within 6 months prior to enrollment.
• Use of any of the following agents within 90 days prior to enrollment: immunomodulatory, cytokine, or growth stimulating factors such as systemic cytotoxic chemotherapy or immune globulin.
• Intent to use immunomodulatory treatment during the study.
• Use of systemic corticosteroids or topical steroids over a total area exceeding 225 cm2 within 30 days prior to enrollment, or anticipated need for periodic use of systemic corticosteroids during the study.
• Note: Participants receiving stable physiologic doses of glucocorticoids, defined as the equivalent of prednisone =10 mg/day, will not be excluded. Participants receiving inhaled, intranasal, topical (as defined), intermittent intra-articular corticosteroids, or topical imiquimod will not be excluded.
• Note: Concomitant use of oral/systemic /intra-articular/inhaled/intranasal corticosteroids is prohibited for participants receiving ritonavir or cobicistat.
• Use of any investigational HIV vaccine or HIV immunotherapy. Note: Exceptions allowed per PI review and approval.
• Prior receipt of any adenovirus Group E-vectored vaccines including those for COVID-19 (i.e. AZD1222/AstraZeneca).
• Prior receipt of a live attenuated vaccine received within 60 days prior to screening (i.e.varicella, measles, mumps, rubella (MMR), and yellow fever).
• Note: Individuals who require live vaccination will delay screening until 60 days after vaccination.
• Use of any other investigational treatment within 6 months prior to enrollment, with the exception of Phase II or higher studies of antiretroviral agents.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

Location

Duke University

Durham, North Carolina, 27703, United States

Location

MeSH Terms

Interventions

Saline Solution; Sodium Chloride

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Cynthia Gay, MD, MPH
• Organization: University of North Carolina at Chapel Hill

cynthia_gay@med.unc.edu

919-843-2726

Study Officials

• Cynthia L Gay, MD, MPH

  University of North Carolina

  PRINCIPAL INVESTIGATOR

• Nilu Goonetilleke, PhD

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 8:8:2 to one of three study arms (C62-M4, C1C62-M3M4, Placebo) and receive study treatment or placebo at Days 0 and 28.

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 3, 2022
• Study Start: October 13, 2022
• Primary Completion: September 12, 2024
• Study Completion: January 10, 2025
• Last Updated: August 24, 2025
• Results First Posted: August 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: 9-36 months after publication
• Access Criteria: Noted above

Locations

US (2)