CMV-MVA Triplex Vaccine for CMV Complications Post-Transplant

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

102 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase II trial studies the safety and how well multi-peptide cytomegalovirus (CMV)-modified vaccinia Ankara (MVA) vaccine works in reducing CMV complications in patients previously infected with CMV and are undergoing a donor hematopoietic cell transplant. CMV is a virus that may reproduce and cause disease and even death in patients with lowered immune systems, such as those undergoing a hematopoietic cell transplant. By placing 3 small pieces of CMV deoxyribonucleic acid (DNA) (the chemical form of genes) into a very safe, weakened virus called MVA, the multi-peptide CMV-MVA vaccine may be able to induce immunity (the ability to recognize and respond to an infection) to CMV. This may help to reduce both CMV complications and reduce the need for antiviral drugs in patients undergoing a donor hematopoietic cell transplant.

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.

What data supports the effectiveness of the CMV-MVA Triplex Vaccine treatment for CMV complications post-transplant?

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 study, patients who received the vaccine had higher levels of these protective cells and fewer needed antiviral drugs to manage CMV. ^{1 2 3 4 5}

Is the CMV-MVA Triplex Vaccine safe for humans?

The CMV-MVA Triplex Vaccine has been tested in healthy adults and recipients of hematopoietic cell transplants, showing it is generally safe with no serious vaccine-related adverse events. It was well-tolerated, with any side effects being mild and temporary. ^{1 2 5 6 7}

How is the CMV-MVA Triplex Vaccine treatment different from other treatments for CMV complications post-transplant?

The CMV-MVA Triplex Vaccine is unique because it uses a modified vaccinia Ankara (MVA) vector to express three key CMV antigens, enhancing both antibody and cellular immune responses. This approach aims to prevent CMV reactivation in transplant recipients without relying on antiviral drugs, which can delay immune recovery. ^{1 2 3 4 5}

Research Team

Ryotaro Nakamura, MD

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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 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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A fusion protein of HCMV IE1 exon4 and IE2 exon5 stimulates potent cellular immunity in an MVA vaccine vector. [2022]

2. United States 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. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Poxvirus Vectored Cytomegalovirus Vaccine to Prevent Cytomegalovirus Viremia in Transplant Recipients: A Phase 2, Randomized Clinical Trial. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Attenuated poxvirus expressing three immunodominant CMV antigens as a vaccine strategy for CMV infection. [2007]

5. England 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

MVA vaccine encoding CMV antigens safely induces durable expansion of CMV-specific T cells in healthy adults. [2021]

7. United States 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. [2021]