CMV-MVA Triplex Vaccine for CMV Complications Post-Transplant

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Antivirals, Alemtuzumab, Vaccines

Disqualifiers: Autoimmune conditions, Pregnancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine designed to prevent complications from CMV, a common virus, in individuals who have had a CMV infection and are receiving a donor stem cell transplant. The CMV-MVA Triplex Vaccine, made from a safe form of a virus with pieces of CMV DNA, aims to boost the immune system to better combat CMV. The study compares the effects of the vaccine against a placebo to evaluate its effectiveness. It targets those who have had CMV, are preparing for a stem cell transplant, and have certain blood conditions like lymphoma or leukemia. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain antiviral medications or other investigational drugs that might affect the study. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that the multi-peptide CMV-MVA vaccine is likely to be safe for humans?

Research has shown that the CMV-Modified Vaccinia Ankara (MVA) vaccine is generally safe. Studies have found that both healthy individuals and those who have undergone blood-forming cell transplants tolerate the vaccine well. No serious side effects have been reported. The vaccine employs a very safe, weakened virus to help the body recognize and combat CMV, a virus that can cause serious problems in people with weakened immune systems. This reduces the need for other treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

The CMV-MVA Triplex Vaccine is unique because it uses a modified vaccinia Ankara virus to deliver multiple peptides specifically targeting cytomegalovirus (CMV) in transplant patients. Unlike standard antiviral drugs that can have significant side effects and resistance issues, this vaccine aims to stimulate the body's immune system to fend off CMV infections more naturally and effectively. Researchers are excited about this approach because it has the potential to offer long-lasting protection with fewer side effects, addressing a critical need for safer CMV management in post-transplant patients.

What evidence suggests that the CMV-MVA Triplex Vaccine might be an effective treatment for CMV complications post-transplant?

Research has shown that the CMV-MVA Triplex Vaccine, which participants in this trial may receive, effectively boosts certain immune cells called T cells in transplant patients. These T cells prevent the cytomegalovirus (CMV) from reactivating, which can cause serious illness in people with weakened immune systems. Studies have found that this vaccine is safe and can reduce the amount of CMV in the blood of patients who have undergone blood stem cell transplants. The vaccine contains small parts of CMV DNA to help the body recognize and fight the virus. Overall, the CMV-MVA Triplex Vaccine is among the most advanced CMV vaccines for transplant patients and shows promise in reducing CMV-related problems. ^{1 2 3 4 5}

Who Is on the Research Team?

Ryotaro Nakamura, MD

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with certain blood cancers or disorders who've had CMV and are undergoing a donor bone marrow transplant. They must understand the study, agree to follow-up procedures for a year, be willing to use contraception, and not have received specific treatments that affect the immune system or CMV within the last 6 months.

Inclusion Criteria

All subjects must have the ability to understand and the willingness to sign a written informed consent

Participant must be willing to comply with study and/or follow-up procedures, including willingness to be followed for one year post-HCT

Myelodysplastic syndrome

Exclusion Criteria

You have received an experimental treatment for CMV (cytomegalovirus) within the past 6 months.

You have received allergy shots as part of your allergy treatment.

You are currently receiving preventive treatment for a viral infection called CMV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive multi-peptide CMV-MVA vaccine or placebo intramuscularly on days 28 and 56 post-HCT

8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including CMV events and GVHD incidence

1 year

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Multi-peptide CMV-Modified Vaccinia Ankara Vaccine

Trial Overview The trial tests if a vaccine made from weakened virus MVA carrying small pieces of CMV DNA can reduce complications from CMV in those getting bone marrow transplants. Participants will either get this experimental vaccine or a placebo to compare outcomes.

How Is the Trial Designed?

Group I: Arm I (multi-peptide CMV-MVA vaccine) Experimental Treatment 2 Interventions

Patients receive multi-peptide CMV-MVA vaccine IM on days 28 and 56 post-HCT.

Group II: Arm II (placebo) Placebo Group 2 Interventions

Patients receive placebo IM on days 28 and 56 post-HCT.

Multi-peptide CMV-Modified Vaccinia Ankara Vaccine is already approved in United States, European Union for the following indications:

Approved in United States as Triplex Vaccine for:

• Prevention of clinically significant CMV viremia in transplant recipients

Approved in European Union as Triplex Vaccine for:

• Prevention of clinically significant CMV viremia in transplant recipients

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

Diavax Biosciences

Industry Sponsor

Trials

1

Recruited

100+

Diavax Biosciences

Collaborator

Trials

1

Recruited

100+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Vaccinating healthy donors with the Triplex vaccine before hematopoietic cell transplant (HCT) significantly increased levels of CMV-specific T cells in recipients, indicating enhanced immune protection against cytomegalovirus (CMV).

The Triplex vaccine was well-tolerated with minimal adverse events, and the approach shows promise for reducing the need for antiviral prophylaxis, which can hinder the development of CMV-specific immunity post-transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell donor vaccination with cytomegalovirus triplex augments frequencies of functional and durable cytomegalovirus-specific T cells in the recipient: A novel strategy to limit antiviral prophylaxis. La Rosa, C., Aldoss, I., Park, Y., et al.[2023]

The study successfully developed a recombinant modified vaccinia Ankara (rMVA) vaccine that expresses three key CMV antigens (sUL55, UL83, and UL123/e4), which are crucial for eliciting both neutralizing antibodies and cellular immunity against CMV infection.

Immunization with the rMVA vaccine in mouse models resulted in strong humoral and cellular immune responses, including high levels of specific antibodies and T cell activation, indicating its potential effectiveness for preventing CMV infection in transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attenuated poxvirus expressing three immunodominant CMV antigens as a vaccine strategy for CMV infection. Wang, Z., La Rosa, C., Lacey, SF., et al.[2007]

The Modified Vaccinia Ankara (MVA) vaccine demonstrated equivalent antibody responses across three different production lots in a phase III trial involving 4005 healthy adults, with a seroconversion rate of 99.8%.

The vaccine was well tolerated, with only 6.0% of MVA recipients reporting trial-related adverse events, and no significant safety concerns, particularly regarding cardiac health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial. Overton, ET., Lawrence, SJ., Wagner, E., et al.[2021]

The developed CMV vaccine, based on modified vaccinia Ankara (MVA), successfully expresses three key CMV antigens and shows strong immunogenicity, stimulating both primary and memory immune responses in mouse models.

In human studies, the vaccine effectively activates existing CMV-specific CD4(+) and CD8(+) T cell responses in healthy CMV-positive individuals and patients shortly after hematopoietic cell transplant, indicating its potential for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector. Wang, Z., Zhou, W., Srivastava, T., et al.[2022]

The CMVPepVax vaccine demonstrated safety in a phase 1b trial with 36 CMV-seropositive patients undergoing stem-cell transplantation, showing no adverse effects on transplant outcomes or unexpected serious adverse events.

Patients receiving the CMVPepVax vaccine had significantly better relapse-free survival compared to those under observation, suggesting potential clinical benefits that warrant further investigation in a phase 2 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial. Nakamura, R., La Rosa, C., Longmate, J., et al.[2022]

In a phase 2 trial involving 102 high-risk CMV-seropositive hematopoietic stem cell transplant recipients, the Triplex vaccine showed a trend towards reducing CMV reactivation, with 9.8% of Triplex recipients experiencing reactivation compared to 19.6% in the placebo group.

The Triplex vaccine was found to be safe, with no serious adverse events or deaths related to the vaccine, and it successfully increased levels of CMV-specific T cells, suggesting it effectively enhances the immune response against CMV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial. Aldoss, I., La Rosa, C., Baden, LR., et al.[2023]

The Triplex vaccine, which uses a modified vaccinia Ankara (MVA) platform to target three key cytomegalovirus (CMV) antigens, was found to be safe in a clinical trial involving 24 healthy adults, with no serious adverse events reported and only mild, transient side effects.

The vaccine successfully induced strong and lasting CMV-specific T-cell responses, even in individuals without prior immunity to CMV, suggesting its potential effectiveness for broader populations, including patients undergoing hematopoietic stem cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MVA vaccine encoding CMV antigens safely induces durable expansion of CMV-specific T cells in healthy adults. La Rosa, C., Longmate, J., Martinez, J., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02506933

NCT02506933 | Multi-antigen CMV-MVA Triplex Vaccine in ... This randomized phase II trial studies the safety and how well multi-peptide cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) vaccine works in reducing ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11215362/

Cytomegalovirus Triplex vaccine in pediatric hematopoietic ... Triplex demonstrated tolerability and immunogenicity in healthy adults, autologous and allogeneic HCT recipients, in whom it reduced CMV viremia. Based on ...

3. nature.com nature.com/articles/s41541-024-00859-3

Highly stable and immunogenic CMV T cell vaccine ... Triplex is the most advanced clinically evaluated CMV vaccine for transplant recipients and is being further tested in multiple Phase 2 clinical ...

4. withpower.com withpower.com/trial/cmv-mva-triplex-vaccine-for-cmv-complications-post-transplant-b57cb

CMV-MVA Triplex Vaccine for CMV Complications Post ... Research shows that the CMV-MVA Triplex Vaccine can boost specific immune cells (T cells) in transplant patients, helping to prevent CMV reactivation. In a ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04060277

Triplex Vaccine in Preventing CMV Infection in Patients ... This phase II trial studies how well Triplex vaccine works in preventing cytomegalovirus (CMV) infection in patients undergoing a hematopoietic stem cell ...