mRNA Vaccine for Cytomegalovirus (CMV)

Recruiting at 5 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: ModernaTX, Inc.

Disqualifiers: Other CMV vaccines, Medical conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 18

291 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

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

What evidence supports the effectiveness of the mRNA-1647 treatment for cytomegalovirus (CMV)?

Research indicates that vaccines can help prevent CMV infections, which are a major cause of disabilities in newborns. Studies have shown that immunity to CMV can reduce disease severity, and animal models have demonstrated that vaccines can prevent CMV-related illnesses, suggesting potential effectiveness for mRNA-1647. ^{1 2 3 4 5}

How is the mRNA-1647 vaccine for CMV different from other treatments?

The mRNA-1647 vaccine is unique because it uses modified mRNA technology to encode CMV glycoproteins, which helps the body produce a strong immune response with both antibodies and T cells. Unlike traditional vaccines, it uses lipid nanoparticles to deliver the mRNA, which is a novel approach for CMV prevention. ^{5 6 7 8 9}

What is the purpose of this trial?

The main purpose of the extension phase of this study is to evaluate the longer-term immune persistence of mRNA-1647 vaccine administered to CMV-seronegative and CMV-seropositive adults who completed Study mRNA-1647-P202 (NCT04232280). For participants in the optional booster phase (BP), the main purpose is to evaluate the long-term immunogenicity and safety of the mRNA-1647 vaccine in both participants receiving a booster dose (BD) and those not receiving a BD, and to additionally evaluate the reactogenicity in participants receiving a BD.

Eligibility Criteria

This trial is for adults who participated in a prior CMV vaccine study (mRNA-1647-P202) and received the mRNA-1647 vaccine, not placebo. They must have completed that study, be in good health as judged by the investigator, understand and agree to follow trial procedures, and provide written consent. Those previously vaccinated with any CMV vaccine other than mRNA-1647 or with conditions affecting safety assessments or adherence to procedures cannot join.

Inclusion Criteria

Understands and agrees to comply with the trial procedures and provides written informed consent.

According to the assessment of the Investigator, is in good general health and is capable of complying with trial procedures.

I was CMV negative at my initial and final study visits.

Exclusion Criteria

Diagnosis or condition that, in the judgment of the Investigator, may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to trial procedures, including any medical, psychiatric, or occupational condition that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results.

I have not received any CMV vaccine except for mRNA-1647.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Primary Extension Phase

Participants who completed Study mRNA-1647-P202 will be followed every 6 months for 3 years to evaluate long-term immune persistence and safety.

3 years

Every 6 months

Optional Booster Phase

Participants may opt to receive a single booster dose of the mRNA-1647 vaccine or be followed without receiving the booster.

12 months

Followed until BP Month 12

Follow-up

Participants are monitored for safety and effectiveness after the optional booster phase.

6 months

Treatment Details

Interventions

• mRNA-1647

Trial Overview The focus of this extension study is on evaluating how long the immune response lasts from the mRNA-1647 vaccine given to both CMV-seronegative and CMV-seropositive adults. It's a continuation for participants who were part of an earlier phase where they received this experimental vaccine against Cytomegalovirus.

Participant Groups

Group I: Primary Extension Phase Experimental Treatment 1 Intervention

CMV-seropositive and CMV-seronegative participants who completed Study mRNA-1647-P202 will be followed every 6 months for 3 years in this study after the final visit in Study mRNA-1647-P202.

Group II: Optional Booster Phase - Observational Group Experimental Treatment 1 Intervention

Participants who opted to enroll into the Observational Group will be followed in the optional BP until BP Month 12.

Group III: Optional Booster Phase - BD Recipients Experimental Treatment 1 Intervention

Participants who opted to enroll into the optional Booster Phase will receive a single mRNA-1647 vaccine dose.

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

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]

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]

Cytomegalovirus (CMV) poses significant health risks to infants and immunocompromised patients, highlighting the need for effective vaccines to prevent CMV-related diseases.

Current research is advancing the development of CMV vaccines, but understanding the specific immune responses needed for effective protection remains crucial before these vaccines can be widely implemented in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in cytomegalovirus vaccine development. Schleiss, M.[2006]

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 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]

References

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

Safety, efficacy, and immunogenicity of a replication-defective human cytomegalovirus vaccine, V160, in cytomegalovirus-seronegative women: a double-blind, randomised, placebo-controlled, phase 2b trial. [2023]

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

Development of cytomegalovirus vaccines: prospects for prevention of congenital CMV infection. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Cytomegalovirus vaccines under clinical development. [2022]

4. England pubmed.ncbi.nlm.nih.gov

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

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

Progress in cytomegalovirus vaccine development. [2006]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Vaccine Vectors Harnessing the Power of Cytomegaloviruses. [2020]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Vaccines for cytomegalovirus. [2019]

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

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