CMV Vaccine for Liver Transplant Recipients

(COLT Trial)

Recruiting at 17 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

Must not be taking: Immunosuppressants, Chemotherapy, Corticosteroids, others

Disqualifiers: Breastfeeding, CMV vaccination, Stem cell transplant, others

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

Compensation: Varies

Number of Visits: 2

416 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine designed to help liver transplant recipients avoid Cytomegalovirus (CMV), a common virus that can cause complications post-transplant. Participants will receive either the CMV-MVA Triplex vaccine or a placebo (a harmless, inactive substance) before their transplant. The trial aims to determine if the vaccine can reduce the need for antiviral medicines in the first 100 days after the transplant. It seeks individuals who will soon receive their first liver transplant and have not previously had CMV. 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 significant medical advancements.

Do I need to stop my current medications for the CMV vaccine trial?

The trial does not specify if you need to stop your current medications. However, if you are taking certain immunosuppressive drugs or have received specific treatments like immunoglobulin or live vaccines recently, you may not be eligible to participate.

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

Research shows that the CMV-MVA Triplex vaccine is being tested for safety and effectiveness. In earlier studies, researchers administered this vaccine to individuals who had stem cell transplants. It strengthened their immune systems without causing serious side effects. Most participants experienced only mild reactions, such as redness at the injection site or slight fatigue.

Since this trial is in a later stage, the vaccine has demonstrated a good safety record so far. Researchers are also testing the vaccine in liver transplant patients to ensure its safety across different groups. While individual reactions may vary, current evidence suggests the CMV-MVA Triplex vaccine is generally safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for cytomegalovirus (CMV) prevention in liver transplant recipients, which typically involves antiviral medications like ganciclovir or valganciclovir, the CMV-MVA Triplex vaccine offers a novel approach. This vaccine is unique because it uses a modified virus, specifically the Modified Vaccinia Ankara (MVA), to help the immune system recognize and fight CMV. Researchers are excited about this treatment because it aims to reduce the dependency on traditional antivirals, which can have significant side effects and resistance issues. Additionally, the vaccine could potentially offer longer-lasting protection against CMV, improving the overall health outcomes for transplant patients.

What evidence suggests that the CMV-MVA Triplex vaccine might be an effective treatment for CMV in liver transplant recipients?

Research has shown that the CMV-MVA Triplex vaccine, which participants in this trial may receive, can help the immune system combat CMV (Cytomegalovirus). Studies have found that this vaccine increases the number of specialized cells in the body that recognize and remember CMV. This is crucial because it helps prevent the virus from causing complications after a liver transplant. The vaccine aims to reduce the need for antiviral drugs, typically used to control the virus. Early results suggest that this vaccine might aid transplant patients by enhancing their immune system's ability to manage CMV. ^{1 2 4 5 6}

Who Is on the Research Team?

Ajit P Limaye, MD

Principal Investigator

University of California, San Francisco: Transplantation

Cindy Fisher, M.D.

Principal Investigator

University of Washington Medical Center: Transplantation

Are You a Good Fit for This Trial?

This trial is for CMV-negative people listed for their first liver transplant, who understand the study and consent to it. They must not have HIV or a history of positive CMV serology, be likely to get a transplant within 1-12 months, and if they can have children, agree to use birth control. People with recent vaccinations, certain immune conditions or treatments, breastfeeding women, those in other trials that affect this one's outcomes or who've had stem cell transplants are excluded.

Inclusion Criteria

Your most recent platelet count must be at least 20,000 cells/mm^3 and cannot have dipped below that number since the last recorded result.

I am expected to get a liver transplant within the next year.

I understand the study and can give my consent.

Exclusion Criteria

You have allergies to any part of the study medicine.

Exclusion criteria required: Dose 2:

I haven't had any cancer treatments like chemotherapy or immunotherapy in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Vaccination

Participants receive two doses of Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine

4 weeks

2 visits (in-person)

Post-transplant Monitoring

Participants are monitored for CMV antiviral therapy (AVT) and preemptive therapy (PET) for CMV disease prevention

100 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• CMV-MVA Triplex

Trial Overview The trial tests the efficacy of two doses of a vaccine called CMV-MVA Triplex against placebo in preventing Cytomegalovirus infection after liver transplantation. Participants will either receive the vaccine or placebo before their transplant and will be monitored for how long they need antiviral therapy post-transplant.

How Is the Trial Designed?

Group I: Vaccine Arm Experimental Treatment 1 Intervention

Participants in this arm will receive two doses of Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine

Group II: Placebo Arm Placebo Group 1 Intervention

Participants will receive two doses of matching placebo of the Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine

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 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]

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]

A novel vaccine strategy using the modified vaccinia virus Ankara (MVA) vector has been developed to stimulate strong immune responses against human cytomegalovirus (HCMV) by targeting multiple antigens, including glycoprotein B (gB) and the pentamer complex.

In mouse studies, this multiantigenic approach elicited potent neutralizing antibodies and robust T cell responses, suggesting it could provide better protection against HCMV infection and disease, particularly for vulnerable populations like pregnant women and transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiantigenic Modified Vaccinia Virus Ankara Vaccine Vectors To Elicit Potent Humoral and Cellular Immune Reponses against Human Cytomegalovirus in Mice. Chiuppesi, F., Nguyen, J., Park, S., et al.[2020]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06075745

NCT06075745 | Cytomegalovirus (CMV) Vaccine in ... The primary objective is to assess the effect of pre-transplant (Tx) Triplex vaccination on duration of CMV antiviral therapy (AVT) within the first 100 days ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT06075745

Cytomegalovirus (CMV) Vaccine in Orthotopic Liver ... The primary objective is to assess the effect of pre-transplant (Tx) Triplex vaccination on duration of CMV antiviral therapy (AVT) within the first 100 days ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10294297/

Hematopoietic stem cell donor vaccination with CMV Triplex ... Hematopoietic stem cell donor vaccination with CMV Triplex augments frequencies of functional and durable CMV-specific T cells in the recipient.

4. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/liver-transplant

UCSD Liver Transplant Clinical Trials for 2025 — San Diego This is a multi-center clinical trial in Cytomegalovirus (CMV) seronegative prospective liver transplant recipients to determine the efficacy of two doses of ...

5. vanderbilt.trialstoday.org vanderbilt.trialstoday.org/trial/NCT06075745

Cytomegalovirus (CMV) Vaccine in Orthotopic Liver Transplant ... The primary objective is to assess the effect of pre-transplant (Tx) Triplex vaccination on duration of CMV antiviral therapy (AVT) within the first 100 days ...

6. 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 ...