A Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Healthy Participants 16 to 40 Years of Age

• ClinicalTrials.gov Identifier: NCT05085366
• Recruitment Status: Active, not recruiting
• First Posted: October 20, 2021
• Last Update Posted: April 24, 2024
• Sponsor: ModernaTX, Inc.
• Information provided by (Responsible Party): ModernaTX, Inc.

Tracking Information

• First Submitted Date: October 7, 2021
• First Posted Date: October 20, 2021
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: October 26, 2021
• Estimated Primary Completion Date: April 6, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 19, 2024)

• Seroconversion From a Negative to a Positive Result for Serum Immunoglobulin G (IgG) Against Antigens not Encoded by mRNA-1647 [ Time Frame: Day 197 (28 days after the third injection) up to Day 887 (24 months after the third injection) ]
• Number of Participants With Solicited Adverse Reactions (ARs) [ Time Frame: Up to 176 days (7 days after each injection) ]
• Number of Participants With Unsolicited Adverse Events (AEs) [ Time Frame: Up to 197 days (28 days after each injection) ]
• Number of Participants With Medically-Attended Adverse Events (MAAEs) [ Time Frame: Day 1 through 6 months after the last injection (up to 347 days) ]
• Number of Participants With Adverse Event of Special Interests (AESIs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 through Day 887 ]
• Geometric Mean Titers (GMTs) of Antigen-Specific Neutralizing Antibody (nAb) [ Time Frame: Month 30 up to Month 54 ]
• Geometric Mean Concentration (GMC) of Binding Antibody [ Time Frame: Month 30 up to Month 54 ]
• Seroconversion From a Negative to a Positive Result for Serum IgG Against Antigens not Encoded by mRNA-1647 [ Time Frame: Day 887 up to Day 1607 ]

Original Primary Outcome Measures (submitted: October 7, 2021)

• Seroconversion From a Negative to a Positive Result for Serum Immunoglobulin G (IgG) Against Antigens not Encoded by mRNA-1647 [ Time Frame: Day 197 (28 days after the third injection) up to Day 887 (24 months after the third injection) ]
• Number of Participants With Solicited Adverse Reactions (ARs) [ Time Frame: Up to 176 days (7 days after each injection) ]
• Number of Participants With Unsolicited Adverse Events (AEs) [ Time Frame: Up to 197 days (28 days after each injection) ]
• Number of Participants With Medically-Attended Adverse Events (MAAEs) [ Time Frame: Day 1 through 6 months after the last injection (up to 347 days) ]
• Number of Participants With Adverse Event of Special Interests (AESIs) and Serious Adverse Events (SAEs) [ Time Frame: Day 1 through end of study (up to Day 887) ]

Current Secondary Outcome Measures (submitted: April 19, 2024)

• GMTs of Antigen-Specific nAb [ Time Frame: Day 1, Months 3, 7, 12, 18, 24, and 30 ]
• GMC of Antigen-Specific Binding Antibody [ Time Frame: Day 1, Months 3, 7, 12, 18, 24, and 30 ]
• Number of Participants with AEs leading to Study Discontinuation, SAEs and Deaths [ Time Frame: Day 887 through end of study (up to Day 1607) ]

• Original Secondary Outcome Measures (submitted: October 7, 2021): Geometric Mean Titers (GMTs) of Antigen-Specific Neutralizing Antibody (nAb) and Binding Antibody [ Time Frame: Day 1, Months 3, 7, 12, 18, 24, and 30 ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Healthy Participants 16 to 40 Years of Age
• Official Title: A Phase 3, Randomized, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1647 Cytomegalovirus (CMV) Vaccine in Healthy Participants 16 to 40 Years of Age
• Brief Summary: The main purpose of this study is to evaluate the efficacy of mRNA 1647 vaccine in CMV-seronegative female participants and to evaluate the safety and reactogenicity of mRNA-1647 vaccine in all participants. The purpose of the Phase 3 extension sub study is to extend the observation period of the main study and to evaluate the longer-term immune persistence of mRNA-1647 vaccine administered to CMV-seronegative females who complete mRNA-1647-P301 main study and to assess for CMV seroconversion in CMV-seronegative participants who did not seroconvert during mRNA-1647-P301 main study. No interventional vaccine will be administered in the extension study.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Observer-blind

Primary Purpose: Prevention

• Condition: Cytomegalovirus Infection

Intervention

• Biological: mRNA-1647
  Lyophilized product that is reconstituted with 0.9% sodium chloride (normal saline)
• Biological: Placebo
  0.9% sodium chloride (normal saline) injection

Study Arms

• Experimental: mRNA-1647
  Participants will receive mRNA-1647 vaccine by intramuscular (IM) injection on Day 1, Day 57, and Day 169.
  Intervention: Biological: mRNA-1647
• Placebo Comparator: Placebo
  Participants will receive mRNA-1647 vaccine matching placebo by IM injection on Day 1, Day 57, and Day 169.
  Intervention: Biological: Placebo

• Publications *: Kadambari S, Evans C, Lyall H. Congenital Infections: Priorities and Possibilities for Resource-limited Settings. Pediatr Infect Dis J. 2023 Feb 1;42(2):e45-e47. doi: 10.1097/INF.0000000000003710. Epub 2022 Sep 12. No abstract available.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 19, 2024): 7454
• Original Estimated Enrollment (submitted: October 7, 2021): 6900
• Estimated Study Completion Date: April 6, 2026
• Estimated Primary Completion Date: April 6, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Participants aged ≥20 years, has or anticipates having direct exposure within 7 months after the planned first dose (in the home, socially, or occupationally) to at least 1 child ≤5 years of age. Direct exposure is defined as either participant is the parent, or participant has close contact (feeding, diaper changes, childcare/supervision) for at least 8 hours per week.
• CMV-seronegative Cohort is CMV-seronegative based on CMV testing at Screening.
• CMV-seropositive Cohort is CMV-seropositive based on CMV testing at Screening.
• Investigator assessment confirms that the participant (including in the case of an emancipated minor), or parent(s)/legally acceptable representative (LAR)(s), as applicable, understand and are willing and physically able to comply with protocol-mandated follow-up including all study visits and procedures anticipated during the 30 month study period.
• Female participants of child-bearing potential: Urine pregnancy test is negative at Screening and negative on the day of the first injection (Day 1). If the participant is sexually active with men, has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first injection (Day 1) and agrees to continue adequate contraception through 3 months following the third study injection (Month 9/Day 257).

Extension substudy:

• All consenting participants in mRNA-1647-P301 main study who were CMV-seronegative at baseline and did not seroconvert during the main study, received at least one study injection, and completed the final study visit in the main study.
• Consenting participants in mRNA-1647-P301 main study who were CMV-seronegative at baseline, received all 3 study injections, and completed the final study visit in the main study.

Key Exclusion Criteria:

• History of a diagnosis or condition that, in the judgment of the Investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures.
• Received or plans to receive any nonstudy vaccine <28 days prior to and after any study injection; in addition, the following criteria for COVID-19 and influenza vaccines apply:
• Any COVID-19 primary vaccination series must have been completed a minimum 28 days prior to receiving any dose of the study injection.
• COVID-19 vaccines (including any booster dose, regardless of manufacturer) must be administered at least 28 days prior to or after any study injection.
• Influenza vaccines may be administered > 14 days prior to or after any study injection.
• Received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to the day of first injection (Day 1) (for corticosteroids, ≥5 milligrams (mg)/day of prednisone equivalent) or plans to do so during the course of the study. Inhaled, nasal, and topical steroids are allowed. Stable immunomodulator regimens used for managing environmental allergies are allowed.
• Receipt of an antiviral with activity against CMV (ganciclovir, valganciclovir, foscarnet, cidofovir, letermovir, acyclovir, valacyclovir) <2 weeks prior to the day of first injection or plans to do so during the course of the study.
• Previous receipt of an investigational CMV vaccine.
• Receipt of systemic immunoglobulins or blood products <3 months prior to the day of first injection.
• Participated in an interventional clinical study <28 days prior to the day of first injection (Day 1) or plans to do so while enrolled in this study.
• Participant has donated ≥450 milliliters (mL) of blood products <28 days prior to Screening.
• Participant is a member of study team or is an immediate family member or household member of study personnel.

Extension substudy:

• Receipt of any CMV vaccine other than mRNA-1647.
• 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 study 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 16 Years to 40 Years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Canada, Estonia, Finland, France, Germany, Israel, Italy, Japan, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT05085366
• Other Study ID Numbers: mRNA-1647-P301; 2020-006051-17 ( EudraCT Number ); 2023-508820-37-00 ( Other Identifier: EU CTR Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: ModernaTX, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: ModernaTX, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: ModernaTX, Inc.
• Verification Date: April 2024