Study to Assess Safety and Ability to Induce Immune Responses of HIV-1 Vaccines M3 and M4 Given Alone or in Combination in HIV-infected Adults

NCT03844386 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: 18-2502U01AI131310-01IGHID 11810
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double blind, randomized, placebo-controlled, parallel design, study in which 24 HIV-infected participants with durable viral suppression will be randomly assigned to receive vaccination with MVA.tHIVconsv3 (M3), MVA.tHIVconsv4 (M4), M3+M4 combined, or placebo. Participants will be randomized 7:7:7:3 to one of four study arms, and receive study treatment or placebo at Day 0. Each enrolled participant will complete the study in approximately 33.5 weeks (8.4 months). The purpose of this study is to find out:

• If it is safe for people to receive injections of two investigational HIV vaccines, called MVAtHIVconsv3 and MVAtHIVconsv4 alone or in combination.
• If giving participants these vaccine doses will increase their immune system's ability to kill HIV virus.

Conditions

HIV-1 Infection

Keywords

HIV-1; Infection; Suppressed; ART; Vaccines; Alone; Combination; Immunogenicity

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 will be used to measure safety where Grade 3 is defined as severe and Grade 4 is defined as potentially life-threatening. Treatment-Related AEs will be assessments that are considered related to study product as possible, probable, or definite as defined in the protocol.

  First day of study treatment through 28 days following vaccination

Secondary Outcomes (1)

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

  First day of study treatment through Day 168 (Week 24) following vaccination

Study Arms (4)

MVA.tHIVconsv3 (M3)

EXPERIMENTAL

Participants in this arm receive one vaccine dose of MVA.tHIVconsv3 (M3) given IM at Day 0

Biological: MVA.tHIVconsv3

MVA.tHIVconsv4 (M4)

EXPERIMENTAL

Participants in this arm receive one vaccine dose of MVA.tHIVconsv4 (M4) given IM at Day 0

Biological: MVA.tHIVconsv4

MVA.tHIVconsv3 (M3)+MVA.tHIVconsv4 (M4)

EXPERIMENTAL

Participants in this arm receive a single combined dose containing each vaccine type MVA.tHIVconsv4 (M3) + MVA.tHIVconsv4 (M4) given IM at Day 0

Biological: MVA.tHIVconsv3; Biological: MVA.tHIVconsv4

Placebo

PLACEBO COMPARATOR

Participants in this arm receive one saline (placebo) dose given IM at Day 0

Other: Placebo

Interventions

MVA.tHIVconsv3 BIOLOGICAL

viral-vector, MVA, expressing immunogens derived from conserved yet immunogenic regions of HIV-1

Also known as: M3

MVA.tHIVconsv3 (M3); MVA.tHIVconsv3 (M3)+MVA.tHIVconsv4 (M4)

MVA.tHIVconsv4 BIOLOGICAL

viral-vector, MVA, expressing immunogens derived from conserved yet immunogenic regions of HIV-1

Also known as: M4

MVA.tHIVconsv3 (M3)+MVA.tHIVconsv4 (M4); MVA.tHIVconsv4 (M4)

Placebo OTHER

The appropriate amount of Sodium Chloride for Injection USP, 0.9% will be drawn into a syringe.

Also known as: Normal saline, Sodium Chloride

Placebo

Eligibility Criteria

• Age: 18 Years - 65 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.
• WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) 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 ≤ 65 years old
• Able and willing to give written informed consent.
• Able and willing to provide adequate locator information.
• Able and willing to comply with time requirements for protocol-specified visits and evaluations.
• Able and willing to commit to all study visits including follow-up through Day 168 (Week 24).
• Continuous ART prior to screening, defined as not missing more than 9 total days and never more than 4 consecutive days in the last 3 months.
• On a stable ART regimen defined as no changes in any ART medication within 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 200mg 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 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, TDF to TAF, ritonavir to cobicistat or separate ART agent dosing to fixed-dose combination), but none within 30 days prior to screening.

You may not qualify if:

• If the HIV provider or study investigator is unable, as assessed by the study PI or protocol team, to construct a fully active alternative regimen based on previous resistance testing and/or treatment history.
• Women of childbearing age/potential must not be breast feeding, pregnant, or planning pregnancy any time from enrollment to 4 months after vaccination at Day 0.
• Body Mass Index (BMI) ≥40 kg/m2
• Untreated syphilis infection (defined as a positive rapid plasma reagin (RPR) without clear documentation of treatment).
• NOTE: In cases of untreated syphilis, participant may rescreen following documentation of adequate treatment of syphilis.
• Current treatment for HCV with antiviral therapy or participants who have received HCV treatment within 6 months prior to screening.
• HIV RNA ≥150 copies/mL in the 6 months prior to screening.
• Received any infusion blood product, immune globulin, or hematopoetic growth factors within 6 months prior to screening.
• Use of any of the following within 90 days prior to screening: immunomodulatory, cytokine, or growth stimulating factors such as systemic cytotoxic chemotherapy, , immune globulin, interferon, cyclosporine, methotrexate, azathioprine, anti-CD25 antibody, IFN, interleukins, interleukin-2 (IL-2), hydroxyurea, thalidomide, sargramostim (granulocyte macrophage-colony stimulating factor \[GM-CSF\]), growth factors, dinitrochlorobenzene (DNCB), thymosin alpha, thymopentin, inosiplex, polyribonucleoside, or diticarb sodium, coumadin, warfarin, or other Coumadin derivative anticoagulants.
• Intent to use immunomodulators (e.g., IL-2, IL-12, interferons or TNF modifiers) during the course of the study.
• Use of systemic corticosteroids or topical steroids over a total area exceeding 15 cm2 within 30 days prior to screening, or anticipated need for periodic use of corticosteroids during the study.
• NOTE: For participants receiving ritonavir or cobicistat, (either as a booster or protease inhibitor \[PI\]) as part of their ART regimen, the concomitant use of oral/systemic/topical/inhaled/ intranasal corticosteroids is prohibited.
• Use of any prior HIV vaccine (prophylactic and/or therapeutic) or HIV immunotherapy.
• Note: exceptions allowed for antibody therapies per PI review and approval.
• Note: exceptions allowed for IGHID 11627 (UNC IRB 17-0468; NCT 03212989) per PI review and approval provided there is greater than 12 months since receipt of study-provided treatment.

Sponsors & Collaborators

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

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

MeSH Terms

Conditions

Infections

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

• Cindy L Gay, MD, MPH

  UNC-Chapel Hill

  PRINCIPAL INVESTIGATOR

• Nilu Goonetilleke, PhD

  UNC-Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study in which both the participant and the investigator are blinded to what the participant receives.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will be randomized 7(M3):7(M4):7(M3+M4):3(Placebo) to one of four study arms, and receive study treatment or placebo at Day 0.

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: February 18, 2019
• Study Start: April 22, 2019
• Primary Completion: November 11, 2021
• Study Completion: April 4, 2022
• Last Updated: August 9, 2022
• Results First Posted: August 9, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)