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Cytomegalovirus InfectionsPhase 2NCT05099965

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

A Phase 2 study testing CMV-MVA Triplex in people with Cytomegalovirus Infections and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
CMV-MVA Triplex
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
94 participants
Where
12 sitesUnited States
Study dates
2 Nov 2021to 8 Oct 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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)
  • Positive CMV immunoglobulin G antibody (IgG) serology, using an FDA-approved assay at any US laboratory that has a CLIA certification or its equivalent at any time prior to study entry.
  • Participants on statin therapy must be stable on the same dose for at least the prior 12 weeks with no anticipated change in statin or dose during the first 48 weeks of study.
  • For individuals of reproductive potential who are able to become pregnant, a negative serum or urine pregnancy test within 24 hours prior to study entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point of care (POC)/CLIA-waived test.
  • NOTE: Individuals of reproductive potential who are able to become pregnant are defined as individuals who have reached menarche and who have not been post-menopausal for at least 12 consecutive months with follicle-stimulating hormone (FSH) ≥40 IU/mL or 24 consecutive months if an FSH is not available, i.e., who have had menses within the preceding 24 months, and have not undergone a sterilization procedure (e.g., hysterectomy, bilateral oophorectomy, or salpingectomy).
  • Participants who are able to impregnate or become pregnant (i.e., of reproductive potential) and are participating in sexual activity that could lead to pregnancy must agree to practice contraception/birth control as indicated below or agree to not participate in a conception process (e.g., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) for at least 14 days prior to the start of the 2-dose vaccine regimen at Entry/Day 0 through at least 60 days after the final vaccination at week 4.
  • Individuals of reproductive potential who are able to become pregnant are defined above. Individuals of reproductive potential who are able to impregnate are defined as individuals who do not have documented azoospermia.
  • Acceptable contraception/birth control for this study includes the use of one or more of the following methods:
  • Condoms with a spermicide
  • Diaphragm or cervical cap with spermicide
  • Intrauterine device (IUD)
  • Hormone-based therapy (e.g., contraceptive pills, patches, implants, rings, or injections)
  • Participants who are not of reproductive potential are eligible without requiring the use of a contraceptive method. Acceptable documentation of lack of reproductive potential includes written documentation or oral communication from a clinician or clinician's staff in source documents of one or more of the following:
  • Surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (documented in medical records or by ultrasound)
  • Postmenopausal with participant reporting at least a 2-year history of amenorrhea or a serum follicle-stimulating hormone (FSH) >30 mIU/mL
  • Surgically sterile following a successful vasectomy
  • NOTE: The participant may not be able to provide written proof of a partner's vasectomy, sterilization, or menopausal status, since the participant's partner is not usually enrolled in the same study to provide consent for release of this information. The verbal report from the participant of their partner's status should be written into the source documents.
  • Ability and willingness of participant to provide informed consent.
  • Willingness of participant to have study samples obtained and stored.
  • NOTE: Although agreement to provide genital secretion at each time-point is required for all participants, inability to produce genital secretion samples at one or more time-point is not exclusionary

Who cannot join

  • 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.
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  • 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.
  • NOTE: Use of daily aspirin is not exclusionary.
  • 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.
  • NOTE: Participants receiving stable physiologic glucocorticoid doses, defined as prednisone ≤10 mg/day or the equivalent, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving inhaled or topical corticosteroids will not be excluded.
  • Intent to use immunomodulators (e.g., IL-2, IL-12, interferons, or TNF modifiers) during the course of the study.
  • Pre-existing cardiovascular disease or diabetes mellitus diagnosed by a medical provider.
  • NOTE 1: History of or current diagnosis of coronary artery disease, angina pectoris, myocardial infarction, previous coronary artery intervention (stenting, angioplasty), peripheral arterial disease (claudication, peripheral arterial angioplasty, or peripheral arterial bypass procedure), cerebrovascular disease (stroke or transient ischemic attack with documented carotid or aortic atherosclerosis), or abdominal aortic aneurysm are exclusionary for this study.
  • NOTE 2: Poorly controlled hypertension, as defined as ≥160/100 mmHg at two occasions, is exclusionary. A pre-existing history of hypertension alone is not exclusionary.
  • For those >40 years of age, a 10-year American College of Cardiology/American Heart Association (ACC/AHA) cardiovascular disease (CVD) risk of >15% (http://www.cvriskcalculator.com/) within 45 days prior to study entry.
  • Receipt of a vaccine within 4 weeks prior to study entry.
  • NOTE: These restrictions apply to any non-MVA-based vaccine, including approved and experimental SARS-Cov-2/COVID-19 vaccines.
  • Receipt of MVA-based vaccines (e.g., for HIV or tuberculosis) within 1 year prior to study entry.
  • Active HIV-associated dementia.
  • Active hepatitis C (defined as hepatitis C virus (HCV) antibody (Ab) positive and HCV RNA detectable within 24 weeks prior to study entry).
  • Active hepatitis B (defined as hepatitis B surface antibody (HBsAb) negative, hepatitis B surface antigen positive (HBsAg), and/or HBV DNA detectable within 24 weeks prior to study entry).
  • NOTE 1: Participants with HBV DNA suppressed on an antiviral regimen containing anti-HBV agents are eligible if they have HBV DNA BLQ within the past 24 weeks or at screening.
  • NOTE 2: Prior documentation of positive HBsAb is acceptable evidence that hepatitis B is not present. If HBsAb is BLQ or documentation is not available, HBsAg and HBcAb should be documented prior to study entry. Participants who have positive HBcAb but BLQ HBsAg and HBsAb (isolated HBcAb positive status) must have HBV DNA polymerase chain reaction (PCR) performed and confirmed as BLQ for participant to be eligible.
  • Suspected active rectal, genital, or pharyngeal chlamydia, gonorrhea, or syphilis (based on screening test results and other clinical information). These participants need to be treated and can be rescreened 30 days or more after treatment. Treatment must be documented.
  • NOTE: Screening for chlamydia and gonorrhea by nucleic acid amplification test (NAAT) only. In persons with positive syphilis enzyme immunoassay (EIA) or rapid plasma regain (RPR), a treponema-based test must be performed for confirmation, however, only evidence of active infection would exclude the subject from the study.
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
  • Acute or serious illness, in the opinion of the site investigator, requiring systemic treatment and/or hospitalization within 14 days prior to entry.
  • NOTE: See protocol for guidelines related to COVID-19 infection.
  • Body temperature >38°C.
  • No evidence of immunity to varicella.
  • NOTE: Serology should only be utilized to verify a history of varicella if the participant does not report a history of chickenpox or have documented completion of the varicella vaccine series.

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • University of Colorado Hospital CRS

    Aurora, Colorado, 80045

  • Alabama CRS

    Birmingham, Alabama, 35222

  • Massachusetts General Hospital CRS (MGH CRS)

    Boston, Massachusetts, 02114

  • Chapel Hill CRS

    Chapel Hill, North Carolina, 27599

  • Case Clinical Research Site

    Cleveland, Ohio, 44106

  • Houston AIDS Research Team CRS

    Houston, Texas, 77009

  • UCLA CARE Center CRS

    Los Angeles, California, 90035-4709

  • Penn Therapeutics, CRS

    Philadelphia, Pennsylvania, 19104

  • University of Pittsburgh CRS

    Pittsburgh, Pennsylvania, 15213

  • UCSD Antiviral Research Center

    San Diego, California, 92103

  • Ucsf Hiv/Aids Crs

    San Francisco, California, 94110

  • Washington University Therapeutics (WT) CRS

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Phase II, Double-Blind, Randomized, Placebo-Controlled Trial to Evaluate the Safety and Immunogenicity of a Modified Vaccinia Ankara (MVA)-Based Anti-Cytomegalovirus (CMV) Vaccine (Triplex®), in Adults With Both Human Immunodeficiency Virus (HIV)-1 and CMV Who Are on Potent Combination ART With Conserved Immune Function

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. two injections of Triplex® administered according to a 4-week, two-injection schedule would be safe over 48 weeks, and
  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.
Read the detailed description

A5355 was a phase II, double-blind, randomized, placebo-controlled, multicenter trial to evaluate the safety and immunogenicity of two injections of MVA-based anti-CMV Vaccine (Triplex®) in adults with both HIV and CMV. Participants were randomized in a 2:1 ratio to receive either two injections of CMV-MVA Triplex® or placebo administered at study Entry/Day 0 and week 4. Participants were followed for 92 weeks after the last scheduled vaccination at week 4, for a total study duration of 96 weeks. During the study, participants had blood, urine, genital secretions, and oral secretions collected.

Enrollment was stratified based on sex and use of gender-affirming hormones. The target sample size was 90 participants (of whom at least 25% were to be female participants not on testosterone or male participants on feminizing hormones).

Being tested
CMV-MVA Triplex, Placebo
Medical subject headings
Cytomegalovirus Infections, HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CMV-MVA TriplexBiological

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

  • PlaceboBiological

    7.5% lactose in phosphate-buffered saline

Study groups in NCT05099965
Study groupRoleWhat they receive
CMV-MVA TriplexActive comparatorCMV-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.
Receives: Biological: CMV-MVA Triplex
PlaceboPlacebo comparatorPlacebo (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.
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From Day 0 through Week 48

  2. 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: Measured at Day 0 and Week 48

Secondary outcomes (10)

  1. Change in IL-6

    The absolute change in IL-6 refers to the value at the follow-up time point minus the value at baseline (Day 0).

    The results for this secondary outcome measure are not yet available as the laboratory testing needed to derive this outcome measure was delayed due to funding issues.

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

  2. Change in sCD163

    The absolute change in sCD163 refers to the value at the follow-up time point minus the value at baseline (Day 0).

    The samples were not tested for sCD163 due to funding issues; therefore, no data for the secondary outcome measure are available for analysis and no future testing is planned.

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

  3. Change in IP-10

    The absolute change in IP-10 refers to the value at the follow-up time point minus the value at baseline (Day 0).

    The results for this secondary outcome measure are not yet available as the laboratory testing needed to derive this outcome measure was delayed due to funding issues.

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

  4. Change in sTNFRII

    The absolute change in sTNFRII refers to the value at the follow-up time point minus the value at baseline (Day 0).

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

  5. Change in D-Dimers

    The absolute change in D-Dimers refers to the value at the follow-up time point minus the value at baseline (Day 0).

    The results for this secondary outcome measure are not yet available as the laboratory testing needed to derive this outcome measure was delayed due to funding issues.

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

  6. CMV DNA in PBMC

    Detectable CMV DNA shedding at each time point (yes/no)

    The results for this secondary outcome measure are not yet available as the laboratory testing needed to derive this outcome measure was delayed due to funding issues.

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

  7. CMV DNA in Urine

    Detectable CMV DNA shedding at each time point (yes/no)

    The results for this secondary outcome measure are not yet available as the laboratory testing needed to derive this outcome measure was delayed due to funding issues.

    Measured: Measured at Weeks 12, 48, and 72

  8. CMV DNA in Genital Secretion

    Detectable CMV DNA shedding at each time point (yes/no)

    The results for this secondary outcome measure are not yet available as the laboratory testing needed to derive this outcome measure was delayed due to funding issues.

    Measured: Measured at Weeks 12,48, and 72

  9. CMV DNA in Oral Secretion

    Detectable CMV DNA shedding at each time point (yes/no)

    The results for this secondary outcome measure are not yet available as the laboratory testing needed to derive this outcome measure was delayed due to funding issues.

    Measured: Measured at Weeks 12,48, and 72

  10. 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.

    Measured: From Day 0 through Week 96

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2021
  2. Study start2 Nov 2021
  3. Primary completion8 Nov 2024
  4. Study completion8 Oct 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
94 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05099965
Sponsor's protocol ID
A5355
Status last verified
Aug 2026
First submitted
1 Sep 2021
Last updated
2 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Individual participant data that underlie results in the publication, after deidentification.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CMV-MVA Triplex in people with Cytomegalovirus Infections and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occurrence of Grade ≥3 AEs (time frame: From Day 0 through Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05099965.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.

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