mRNA-1647 Vaccine for Cytomegalovirus Infection

Overseen By Moderna WeCare Team

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ModernaTX, Inc.

Must not be taking: Alemtuzumab, Antithymocyte globulin

Disqualifiers: HIV, Ex-vivo T cell depletion, others

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

Compensation: Varies

Number of Visits: 4

Duration: Approximately 6 months

224 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new vaccine called mRNA-1647 to help patients who have had a bone marrow transplant avoid CMV infections. The vaccine works by teaching the immune system to recognize and fight the virus.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the study team or your doctor.

What data supports the effectiveness of the mRNA-1647 vaccine for Cytomegalovirus infection?

The success of mRNA vaccines against COVID-19 and their promising results in cancer treatment suggest that mRNA technology can effectively stimulate the immune system. This indicates potential for the mRNA-1647 vaccine to be effective against Cytomegalovirus by using similar mechanisms to boost immune responses. ^{1 2 3 4 5}

Is the mRNA-1647 CMV vaccine safe for humans?

The mRNA-1647 CMV vaccine has been tested in clinical trials, and no serious safety concerns have been reported. Participants experienced mild reactions, such as pain at the injection site, similar to those who received a placebo. ^{6 7 8 9 10}

What makes the mRNA-1647 CMV vaccine treatment unique?

The mRNA-1647 CMV vaccine is unique because it uses lipid nanoparticles to deliver modified mRNA encoding CMV glycoproteins, which helps the body produce a strong immune response with both antibodies and T cells. This approach is different from traditional vaccines and aims to provide protection against CMV infection in various populations, including pregnant women and transplant patients. ^{6 7 10 11 12}

Eligibility Criteria

This trial is for adults who've had a bone marrow transplant, are at high risk for CMV infection, and have working major organs. They must not be pregnant or breastfeeding, agree to use contraception, and can't have HIV or recent treatments that weaken the immune system.

Inclusion Criteria

CMV-seropositive, defined as a documented positive test for anti-CMV IgG

Persons who are not currently breast/chestfeeding

I am at high risk for CMV due to my stem cell transplant type or donor match.

Exclusion Criteria

I am at low risk for CMV after a stem cell transplant from a related or unrelated donor.

Receipt of prior investigational CMV vaccines or participation in another CMV therapeutic trial that may interfere with study outcome measures as determined by the Investigator

A documented positive HIV test

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive mRNA-1647 or placebo by intramuscular injection on Day 42, Day 67, and Day 92, with a booster dose on Day 180

Approximately 6 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Regular monitoring visits

Treatment Details

Interventions

• mRNA-1647 Cytomegalovirus (CMV) Vaccine
• Placebo

Trial Overview The study tests mRNA-1647 vaccine's effectiveness in preventing significant CMV infections after stopping standard anti-CMV drugs post-transplant. Participants will either receive the vaccine or a placebo to compare results.

Participant Groups

Group I: mRNA-1647 Experimental Treatment 1 Intervention

Participants will receive mRNA-1647 by intramuscular (IM) injection on Day 42, Day 67, and Day 92, and a booster dose on Day 180.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive mRNA-1647 matching placebo by IM injection on Day 42, Day 67, and Day 92, and a booster dose on Day 180.

Who Is Running the Clinical Trial?

ModernaTX, Inc.

Lead Sponsor

Trials

127

Recruited

66,790,000+

Dr. Stephen Hoge

ModernaTX, Inc.

Chief Medical Officer

MD from Harvard Medical School

Stéphane Bancel

ModernaTX, Inc.

Chief Executive Officer since 2011

MBA from Harvard Business School, MSc in Engineering from École Centrale Paris

Findings from Research

CureVac's two-component mRNA vaccines induce a strong and balanced immune response against tumors, leading to complete protection against antigen-positive tumor cells after just two intradermal vaccinations.

Early clinical trials in prostate cancer and non-small cell lung carcinoma patients demonstrate that these mRNA vaccines are safe, well tolerated, and highly immunogenic, suggesting their potential as an effective cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect. Fotin-Mleczek, M., Zanzinger, K., Heidenreich, R., et al.[2020]

The COVID-19 pandemic has significantly accelerated the development and approval of mRNA vaccines, marking a historic milestone in vaccine technology.

Regulatory agencies require detailed chemistry, manufacturing, and control (CMC) information to ensure the safety and quality of mRNA vaccines, especially as new virus variants emerge and the development process evolves rapidly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulatory perspective for quality evaluation of lipid nanoparticle-based mRNA vaccines in China. Lu, J., Wei, W., He, W.[2023]

Synthetic mRNA vaccines are revolutionizing cancer treatment by enabling the development of personalized immunotherapies that target specific tumor antigens based on individual genetic profiles.

New delivery systems, including peptide and lipid-based carriers, are being developed to enhance the effectiveness of mRNA vaccines, potentially improving immune responses against solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Editorial: mRNA Vaccines and Immunotherapy in Oncology: A New Era for Personalized Medicine. Parums, DV.[2023]

Amplifying mRNA vaccines show great promise in cancer treatment due to their ability to induce strong and long-lasting immune responses at low doses, which can effectively target and kill tumor cells.

The success of mRNA vaccines in combating COVID-19 has inspired their application in cancer therapy, highlighting the potential for innovative vaccine designs to overcome challenges in tumor-specific immunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amplifying mRNA vaccines: potential versatile magicians for oncotherapy. Hu, C., Liu, J., Cheng, F., et al.[2023]

mRNA vaccines have shown great promise in treating infectious diseases and cancer, with significant advantages over conventional cancer vaccines, such as efficient immune response production, lower side effects, and reduced costs.

The recent success of SARS-CoV-2 mRNA vaccines has spurred a surge in research for mRNA cancer vaccines, highlighting their potential in tumor treatments and the need to address ongoing challenges in the field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mRNA vaccine in cancer therapy: Current advance and future outlook. Li, Y., Wang, M., Peng, X., et al.[2023]

Congenital cytomegalovirus (CMV) infection is the leading infectious cause of disability in newborns, highlighting the urgent need for effective vaccination to protect vulnerable populations.

Current research shows promise for a recombinant CMV glycoprotein B (gB) vaccine, which has demonstrated some efficacy in preventing CMV infection in young women, adolescents, and CMV-seronegative transplant recipients, indicating potential for broader immunization strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytomegalovirus vaccines under clinical development. Schleiss, MR.[2022]

The CMV vaccine using the envelope glycoprotein gB combined with the MF59 adjuvant was found to be more immunogenic than the same vaccine with alum, indicating a stronger immune response.

The trial, which involved a phase I study design with no serious adverse events reported, showed that the vaccine was safe, with only mild local and systemic reactions, suggesting it could be a promising candidate for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A subunit cytomegalovirus vaccine based on recombinant envelope glycoprotein B and a new adjuvant. Pass, RF., Duliegè, AM., Boppana, S., et al.[2008]

Recent trials have shown that the gB/MF59 vaccine is 50% effective in preventing cytomegalovirus (CMV) infection in healthy postpartum women, indicating a promising step towards a safe vaccine.

In immunocompromised patients, both the gB/MF59 and TransVax DNA vaccines reduced the duration of viraemia and the need for antiviral treatments, suggesting they could significantly improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytomegalovirus vaccine: phase II clinical trial results. Rieder, F., Steininger, C.[2022]

The V160 CMV vaccine was found to be generally well-tolerated in both CMV-seronegative and seropositive adults, with no serious adverse events reported and only mild-to-moderate injection-site and systemic reactions observed.

The vaccine successfully elicited robust neutralizing antibody responses and T-cell activation, maintaining these levels for up to 12 months, indicating strong immunogenicity similar to that seen after natural CMV infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects. Adler, SP., Lewis, N., Conlon, A., et al.[2020]

The study shows that a vaccine using lipid nanoparticles (LNP) with modified mRNA encoding CMV glycoproteins can generate strong and lasting neutralizing antibodies in both mice and nonhuman primates, indicating potential effectiveness against CMV infection.

An additional mRNA vaccine targeting the CMV T cell antigen pp65 was developed, which successfully produced robust T cell responses, suggesting that this mRNA/LNP platform can be tailored for different populations, such as pregnant women and transplant recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity. John, S., Yuzhakov, O., Woods, A., et al.[2018]

A recent trial of a subunit glycoprotein B (gB) vaccine with the adjuvant MF59 showed promise in reducing CMV infections in postpartum women, indicating potential for effective CMV vaccination.

Various innovative vaccine strategies, including replicons and DNA vaccines, are currently in clinical trials, but the ideal formulation for a CMV vaccine is still being determined.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccines for cytomegalovirus. Bernstein, DI.[2019]

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]

References

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Highly potent mRNA based cancer vaccines represent an attractive platform for combination therapies supporting an improved therapeutic effect. [2020]

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Regulatory perspective for quality evaluation of lipid nanoparticle-based mRNA vaccines in China. [2023]

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Editorial: mRNA Vaccines and Immunotherapy in Oncology: A New Era for Personalized Medicine. [2023]

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Amplifying mRNA vaccines: potential versatile magicians for oncotherapy. [2023]

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mRNA vaccine in cancer therapy: Current advance and future outlook. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Cytomegalovirus vaccines under clinical development. [2022]

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

A subunit cytomegalovirus vaccine based on recombinant envelope glycoprotein B and a new adjuvant. [2008]

8. England pubmed.ncbi.nlm.nih.gov

Cytomegalovirus vaccine: phase II clinical trial results. [2022]

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Phase 1 Clinical Trial of a Conditionally Replication-Defective Human Cytomegalovirus (CMV) Vaccine in CMV-Seronegative Subjects. [2020]

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Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity. [2018]

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