CMV-MVA Triplex Vaccine for Cytomegalovirus

No longer recruiting at 12 trial locations

Overseen By Sara Gianella, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: Antiretrovirals

Must not be taking: Anti-CMV drugs, Immunomodulators

Disqualifiers: Autoimmune disorders, Cardiovascular disease, Diabetes, Hepatitis, others

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

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine, CMV-MVA Triplex®, to determine its ability to prevent cytomegalovirus (CMV) in people living with HIV. Participants will receive either the vaccine or a placebo (a harmless substance used as a control) through two injections. The trial seeks individuals who have maintained consistent HIV treatment for at least 48 weeks and have controlled HIV levels. The goal is to evaluate the vaccine's effectiveness and safety in reducing CMV infections in this specific group. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in HIV care.

Will I have to stop taking my current medications?

The trial does not specify that you need to stop taking your current medications. However, you must be on a stable ART regimen for at least 48 weeks before joining the study, and certain medications like those with anti-CMV activity should not be used within 14 days prior to the study. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the CMV-MVA Triplex® vaccine is safe and well-tolerated in people. Studies have demonstrated that this vaccine effectively reduces cytomegalovirus (CMV) levels in both healthy individuals and those with weakened immune systems.

The vaccine has been tested in various groups, including individuals who have undergone bone marrow transplants and those with AIDS. It has proven safe and helps the body combat the virus by triggering a strong immune response. Reports indicate that it activates T cells, a type of immune cell, to specifically target CMV.

Overall, these studies have reported no serious safety issues. The vaccine is considered safe and effective in strengthening the immune system against CMV. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Cytomegalovirus (CMV) which generally involve antiviral medications, the CMV-MVA Triplex® vaccine offers a preventive approach. This vaccine is unique because it uses a modified vaccinia Ankara (MVA) virus to deliver CMV antigens, aiming to stimulate the immune system to recognize and fight CMV more effectively. By targeting CMV before it can cause infection, this vaccine has the potential to reduce the need for long-term antiviral drug use and its associated side effects. Researchers are excited about this treatment because it represents a shift from reactive to proactive CMV management, which could significantly improve quality of life for those at risk.

What evidence suggests that the CMV-MVA Triplex® vaccine might be an effective treatment for cytomegalovirus?

Research has shown that the CMV-MVA Triplex vaccine, which participants in this trial may receive, holds promise for boosting immunity against cytomegalovirus (CMV). Studies have found that the vaccine is safe and can activate strong T cell responses, crucial for fighting CMV infections. In adults and individuals with weakened immune systems, the vaccine effectively reduced CMV levels in the blood, known as CMV viremia. This suggests that the vaccine could help prevent CMV-related health issues, especially in those with compromised immune systems. Overall, these findings highlight the potential of the CMV-MVA Triplex vaccine to enhance immune protection against CMV. ^{2 3 5 6 7}

Who Is on the Research Team?

Sara Gianella, MD

Principal Investigator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Are You a Good Fit for This Trial?

Adults aged 18-65 with stable HIV on antiretroviral therapy (ART) for at least 48 weeks, a CD4+ count over 250 cells/μL, and an undetectable viral load. They must not be pregnant or breastfeeding, agree to use contraception, have no history of severe allergies to vaccine components or autoimmune disorders, and cannot be using certain medications like anticoagulants.

Inclusion Criteria

Specific laboratory values within specified ranges

Positive CMV IgG antibody serology

HIV-1 infection confirmed by licensed tests

Exclusion Criteria

Suspected active chlamydia, gonorrhea, or syphilis

Breastfeeding

I have heart disease or diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two injections of CMV-MVA Triplex® or placebo at study Entry/Day 0 and week 4

4 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and immunogenicity with follow-up visits in person or by phone

96 weeks

Multiple visits (in-person or by phone)

What Are the Treatments Tested in This Trial?

Interventions

• CMV-MVA Triplex®
• Placebo

Trial Overview The trial is testing the safety and immune response to a CMV vaccine called Triplex® in people living with HIV. Participants are randomly assigned in a 2:1 ratio to receive either two doses of the Triplex® vaccine or a placebo via muscle injections four weeks apart.

How Is the Trial Designed?

Group I: Vaccine Group Active Control 1 Intervention

60 participants will receive CMV-MVA Triplex® containing 5 x 108 plaque-forming unit (pfu) ±0.5 x 108 pfu of MVA Vaccine Encoding CMV Antigens by intramuscular (IM) deltoid injections.

Group II: Placebo Group Placebo Group 1 Intervention

30 participants will receive a volume of placebo (7.5% Lactose in phosphate-buffered saline \[PBS\]) that matches the volume of the active vaccine injection by IM deltoid injections.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

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]

Certain high-risk groups, such as HIV-infected individuals, transplant patients, and newborns, are particularly vulnerable to diseases caused by human cytomegalovirus (CMV), highlighting the need for effective vaccination strategies.

While there are currently no licensed CMV vaccines for humans, various vaccine approaches, including protein subunit, DNA, and live attenuated vaccines, are being tested in clinical trials, showing promise in inducing protective immune responses against CMV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress toward an elusive goal: current status of cytomegalovirus vaccines. Schleiss, MR., Heineman, TC.[2007]

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]

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 clinical trial involving 20 patients with lymphoma or myeloma, the Triplex vaccine significantly enhanced the reconstitution of adaptive natural killer (NK) cells and CMV-specific T cells after autologous hematopoietic cell transplantation (auto-HCT), particularly in CMV-seronegative patients.

The vaccine led to a notable increase in adaptive NK cells and CMV-specific T cells, suggesting a potential for improved immune response post-transplant, although further research is needed to assess the clinical benefits of these immune enhancements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CMV Triplex Vaccine to Enhance Adaptive NK and T-cell Reconstitution After Autologous Hematopoietic Cell Transplantation. Rashidi, A., La Rosa, C., Curtsinger, J., et al.[2023]

A universal childhood CMV vaccine could significantly reduce congenital CMV disease by preventing transmission from infected children to mothers, highlighting the importance of early vaccination.

Clinical trials for CMV vaccines should focus on practical endpoints, such as protection against cCMV infection in women and CMV viremia levels in stem cell transplant recipients, to better assess vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Priorities for CMV vaccine development. Krause, PR., Bialek, SR., Boppana, SB., et al.[2022]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06059391

NCT06059391 | CMV-MVA Triplex Vaccination in HLA ... This phase II clinical trial tests how well the cytomegalovirus-modified vaccinica Ankara (CMV-MVA) Triplex vaccine given to human leukocyte antigens (HLA) ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-03633

A Vaccine (CMV-MVA Triplex Vaccine) for the ... Giving CMV-MVA triplex vaccine may be safe, tolerable and/or effective in enhancing cytomegalovirus (CMV)-specific immunity and preventing CMV viremia in ...

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

Highly stable and immunogenic CMV T cell vaccine ... Triplex has been shown to be safe and to elicit potent antigen-specific T cell responses in healthy and immunocompromised individuals. It was ...

6. helocyte.com helocyte.com/development-pipeline/triplex/

Triplex The study demonstrated that Triplex is both safe and highly immunogenic, inducing robust expansion of CD4+ and CD8+ T-cells specific for each immuno-dominant ...

7. ashpublications.org ashpublications.org/blood/article/126/23/3108/135386/Safety-Maximum-Tolerated-Dose-and-Immunogenicity

Safety, Maximum Tolerated Dose and Immunogenicity of CMV ... Replication-defective MVA is safe, well tolerated and strongly immunogenic when given to HCT recipients or AIDS patients. We developed a ...