CMV-MVA Triplex Vaccine for Cytomegalovirus

Recruiting at 11 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

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Participants will be 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. Vaccine Group: 60 participants will receive 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. Placebo Group: 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.

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 the CMV-MVA Triplex Vaccine safe for humans?

The CMV-MVA Triplex Vaccine has been tested in healthy adults and transplant recipients, showing it is generally safe with no serious side effects related to the vaccine. Some mild and temporary reactions were observed, but overall, it was well-tolerated. ^{1 2 3 4 5}

How is the CMV-MVA Triplex vaccine treatment different from other treatments for cytomegalovirus?

The CMV-MVA Triplex vaccine is unique because it uses a modified vaccinia Ankara (MVA) vector to enhance CMV-specific T cells, helping prevent CMV reactivation in transplant recipients. This approach is novel as it focuses on boosting the immune response rather than relying solely on antiviral drugs, which can delay CMV-specific immunity. ^{2 3 4 6 7}

What data supports the effectiveness of the CMV-MVA Triplex treatment for cytomegalovirus?

Research shows that the CMV-MVA Triplex vaccine helps boost specific immune cells that fight cytomegalovirus (CMV) in patients who have had a stem cell transplant. This vaccine was well-tolerated and reduced the reactivation of CMV, which means it could help prevent CMV-related issues in these patients. ^{2 3 4 8 9}

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

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]

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]

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]

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 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]

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]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Priorities for CMV vaccine development. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Progress toward an elusive goal: current status of cytomegalovirus vaccines. [2007]

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. 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]

5. England pubmed.ncbi.nlm.nih.gov

Towne-vaccine-induced prevention of cytomegalovirus disease after renal transplants. [2019]

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

CMV Triplex Vaccine to Enhance Adaptive NK and T-cell Reconstitution After Autologous Hematopoietic Cell Transplantation. [2023]

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

Effect of previous or simultaneous immunization with canarypox expressing cytomegalovirus (CMV) glycoprotein B (gB) on response to subunit gB vaccine plus MF59 in healthy CMV-seronegative adults. [2013]

9. China pubmed.ncbi.nlm.nih.gov

The immunological underpinnings of vaccinations to prevent cytomegalovirus disease. [2018]