Trial to Evaluate the Safety and Immunogenicity of a Modified Vaccinia Ankara (MVA)-Based Anti-Cytomegalovirus (CMV) Vaccine (Triplex®)

NCT05099965 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: A5355
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 12

Brief Summary

A5355 was a randomized, placebo-controlled study conducted at US sites to evaluate the safety and immunogenicity of two injections of the study drug Modified Vaccinia Ankara (MVA)-based anti-Cytomegalovirus (CMV) Vaccine (Triplex®) in adults with both HIV and CMV. Participants were randomly assigned to receive either two injections of Triplex® or placebo at Entry/Day 0 and week 4. The primary hypotheses of this study were:

1. 1.two injections of Triplex® administered according to a 4-week, two-injection schedule would be safe over 48 weeks, and
2. 2.blood plasma levels of soluble receptors for tumor necrosis factor type II (sTNFRII) would decrease over the first 48 weeks in participants receiving the active vaccine compared to placebo.

Conditions

Cytomegalovirus Infections; HIV Infections; Vaccine

Outcome Measures

Primary Outcomes (2)

• Occurrence of Grade ≥3 AEs

  Adverse events were graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017. Adverse events were graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. Higher scores/grades mean a worse outcome.

  From Day 0 through Week 48

• Change in sTNFRII

  The absolute change in sTNFRII at Week 48 is the value at Week 48 minus the value at baseline (Day 0). Linear regression was used to estimate the mean change by treatment arm adjusted for the sex and hormone use stratification factor.

  Measured at Day 0 and Week 48

Secondary Outcomes (10)

• Change in IL-6

  Measured at Day 0 and Weeks 12, 24, 48 and 72

• Change in sCD163

  Measured at Day 0 and Weeks 12, 24, 48, 72

• Change in IP-10

  Measured at Day 0 and Weeks 12, 24, 48, 72

• Change in sTNFRII

  Measured at Day 0 and Weeks 12, 24, 72

• Change in D-Dimers

  Measured at Day 0 and Weeks 12, 24, 48, 72

Other Outcomes (7)

• Change in pp65-specific CD137+ CD8+ T Cells

  From Day 0 to week 12

• Change in IE1-specific CD137+ CD8+ T Cells

  From Day 0 to Week 12

• Change in IE2-specific CD137+ CD8+ T Cells

  From Day 0 to week 12

Study Arms (2)

CMV-MVA Triplex

ACTIVE COMPARATOR

CMV-MVA Triplex® containing 5 x 10\^8 plaque-forming unit (pfu) ±0.5 x 10\^8 pfu of MVA Vaccine Encoding CMV Antigens by intramuscular (IM) deltoid injections at Entry/Day 0 and week 4.

Biological: CMV-MVA Triplex

Placebo

PLACEBO COMPARATOR

Placebo (7.5% lactose in phosphate-buffered saline) that matched the volume of the active vaccine injection by IM deltoid injections at Entry/Day 0 and week 4.

Biological: Placebo

Interventions

CMV-MVA Triplex BIOLOGICAL

5 x 10\^8 plaque-forming unit (pfu) ±0.5 x 10\^8 pfu of MVA Vaccine

CMV-MVA Triplex

Placebo BIOLOGICAL

7.5% lactose in phosphate-buffered saline

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-1 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 load.
• NOTE: The term "licensed" refers to a US FDA-approved kit, which is required for all IND studies.
• 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. 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.
• Currently on continuous ART for ≥48 weeks prior to study entry. This is defined as continuous ART consisting of at least 2 nucleoside reverse transcriptase inhibitors (NRTIs) and either a protease inhibitor boosted with low dose ritonavir or with cobicistat, an integrase inhibitor, or an non-nucleoside reverse transcriptase inhibitor (NNRTI) for the 48-week period prior to study entry with no ART interruption longer than 7 consecutive days.
• NOTE 1: Other ART regimens may be acceptable. For a list of acceptable ART regimens, please see the A5355 PSWP. For any regimens not listed, sites must consult the protocol team.
• NOTE 2: Modifications to ART regimens prior to study entry are allowable except for the time period noted in the protocol.
• HIV-1 RNA level \<75 copies/mL (or below the limit of detection of clinically certified assays) for at least 48 weeks prior to study entry, using an FDA-approved assay performed by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent. The participant must have a minimum of two values in the last 48 weeks obtained \>30 days apart, with the most recent value obtained within 45 days prior to entry.
• NOTE: Single determinations that are between the assay quantification limit and 500 copies/mL (i.e., "blips") are allowed as long as the preceding and subsequent determinations are both below the level of quantification. The screening value may serve as the subsequent undetectable value following a blip.
• CD4+ cell count \>250 cells/μL, obtained within 45 days prior to study entry at any US laboratory that has a CLIA certification or its equivalent.
• The following laboratory values, obtained within 45 days prior to entry (unless otherwise noted) by any US laboratory that has a CLIA certification or its equivalent:
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 75,000/mm3
• Estimated Glomerular Filtration Rate (eGFR) \>50 mL/min/1.73m2 or creatinine clearance (CrCl) \>50 mL/min using the Cockcroft-Gault equation on the FSTRF website.
• Aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), and alkaline phosphatase ≤ 3 X ULN
• Hemoglobin A1c (HgbA1c) \<6.5% (within 90 days prior to entry)

You may not qualify if:

• Unapproved modification in ART regimen within the 12 weeks prior to study entry, or anticipated/intended modification of ART during the study period.
• NOTE: Certain modifications of ART doses during the 12 weeks prior to study entry are permitted. In addition, change in formulation (e.g., from standard formulation to fixed-dose combination) is allowed within 12 weeks prior to study entry. A within-class single drug substitution (e.g., switch from nevirapine to efavirenz, from atazanavir to darunavir, from TDF to TAF) is allowed within 12 weeks prior to study entry, with the exception of a switch between any other NRTI to/from abacavir. No other changes in ART within the 12 weeks prior to study entry are permitted.
• Nadir CD4+ cell count \<100 cells/μL performed by any US laboratory that has a CLIA certification or its equivalent.
• NOTE: If documentation is not available, then participant recall is acceptable, subject to the referring physician's confirmation that the participant's recall is consistent with the referring physician's knowledge and judgment.
• Breastfeeding.
• History of or active autoimmune disorders, including but not limited to inflammatory bowel diseases, scleroderma, severe psoriasis, myocarditis, uveitis, pneumonitis, systemic lupus erythematosus, rheumatoid arthritis, optic neuritis, myasthenia gravis, adrenal insufficiency, untreated hypothyroidism and/or hyperthyroidism, autoimmune thyroiditis, or sarcoidosis.
• NOTE: For questions related to the definition of autoimmune disorders, sites should contact the A5355 clinical management committee (CMC) per the Study Management section.
• Known allergy/sensitivity or any hypersensitivity to components of the vaccine.
• Use of anticoagulants, bleeding disorder, or condition associated with prolonged bleeding time that would contraindicate IM injection.
• Use of drugs with anti-CMV activity within 14 days prior to study entry (including but not limited to ganciclovir, valganciclovir, foscarnet, cidofovir, and letermovir).
• NOTE: Acyclovir and valacyclovir may be used.
• Any episode of symptomatic CMV disease within 12 months prior to study entry.
• Previous receipt at any time of any experimental CMV vaccine.
• Use of any infusion blood product or immune globulin within 3 months prior to study entry.
• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine, and monoclonal antibodies), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry.

Sponsors & Collaborators

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

Study Sites (12)

Alabama CRS

Birmingham, Alabama, 35222, United States

Location

UCLA CARE Center CRS

Los Angeles, California, 90035-4709, United States

Location

UCSD Antiviral Research Center

San Diego, California, 92103, United States

Location

Ucsf Hiv/Aids Crs

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599, United States

Location

Case Clinical Research Site

Cleveland, Ohio, 44106, United States

Location

Penn Therapeutics, CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Houston AIDS Research Team CRS

Houston, Texas, 77009, United States

Location

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.1, July 2017.
• Manual for Expedited Reporting of Adverse Events to Division of AIDS

MeSH Terms

Conditions

Cytomegalovirus Infections; HIV Infections

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@dlhcorp.com

(301) 628-3348

Study Officials

• Sara Gianella, MD

  Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2021
• First Posted: October 29, 2021
• Study Start: November 2, 2021
• Primary Completion: November 8, 2024
• Study Completion: October 8, 2025
• Last Updated: May 14, 2026
• Results First Posted: May 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the Advancing Clinical Therapeutics Globally (ACTG) by NIH
• Access Criteria: With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG. For what types of analyses? To achieve aims in the proposal approved by the ACTG. By what mechanism will data be made available? Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data.

Locations

US (12)