CMV Vaccine for Liver Transplant Recipients

(COLT Trial)

Recruiting at 17 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

This is a multi-center clinical trial in Cytomegalovirus (CMV) seronegative prospective liver transplant recipients to determine the efficacy of two doses of Cytomegalovirus-Modified Vaccinia Ankara (CMV-MVA) Triplex CMV vaccine pre-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 post-Tx in CMV seropositive donor (D+) and seronegative (R-) (D+R-) liver transplant recipients (LTxRs). A protocol-mandated preemptive therapy (PET) will be used for CMV disease prevention in D+R- LTxRs.

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.

What data supports the effectiveness of the CMV-MVA Triplex treatment for liver transplant recipients?

Research shows that the CMV-MVA Triplex vaccine can boost specific immune cells that fight cytomegalovirus (CMV) in transplant recipients, reducing the need for antiviral drugs. In studies with other types of transplants, this vaccine increased important immune responses and helped control CMV reactivation. ^{1 2 3 4 5}

Is the CMV-MVA Triplex vaccine safe for humans?

The CMV-MVA Triplex vaccine has been tested in clinical trials and was found to be well-tolerated with limited adverse events in both healthy adults and transplant recipients, suggesting it is generally safe for humans. ^{1 2 3 4 5}

How is the CMV-MVA Triplex vaccine treatment different from other treatments for CMV in liver transplant recipients?

The CMV-MVA Triplex vaccine is unique because it uses a modified vaccinia Ankara (MVA) vector to deliver three key CMV antigens, enhancing both antibody and T-cell responses to prevent CMV reactivation, which is different from standard antiviral drugs that mainly target the virus directly. ^{2 3 4 5 6}

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

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• CMV-MVA Triplex (Cancer Vaccine)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

References

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

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

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. United States 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. [2020]

5. 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]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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