Cytomegalovirus Infection
Conditions
Keywords
mRNA-1647, Moderna, Cytomegalovirus, CMV, Cytomegalovirus Vaccine, Cytomegalovirus Infections, Cytomegalovirus Congenital, Virus Diseases, Infection Viral, DNA Virus Infections, Messenger RNA
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 substudy is to extend the observation period of the main study and to assess the longer-term immunogenicity, efficacy, and safety of the mRNA-1647 vaccine against primary CMV infection in healthy females who were CMV-seronegative at Baseline of the mRNA-1647-P301 main study (including participants who remain CMV-seronegative upon entry into the extension substudy and participants who seroconverted during the main study). The extension substudy will also evaluate the immune persistence and safety of mRNA-1647 in a subset of female participants who were CMV-seropositive at Baseline of the main study. No interventional vaccine will be administered in the extension substudy.
Interventions
BIOLOGICALmRNA-1647
Lyophilized product that is reconstituted with 0.9% sodium chloride (normal saline)
BIOLOGICALPlacebo
0.9% sodium chloride (normal saline) injection
Sponsors
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Observer-blind
Eligibility
Sex/Gender
FEMALE
Age
16 Years to 40 Years
Healthy volunteers
Yes
Inclusion 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 who were CMV-seronegative at Baseline in the mRNA-1647-P301 main study (including those who did seroconvert and did not seroconvert during the main study), received at least one study injection in the main study but did not withdraw study consent, and completed the final study visit in mRNA-1647-P301 main study. * Consenting participants in mRNA-1647-P301 main study who were CMV-seropositive at Baseline, received all 3 study injections, did not withdraw study consent, 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Systemic Viral Dissemination | Month 30 up to Month 54 |
| Number of Participants With Unsolicited Adverse Events (AEs) | Up to 197 days (28 days after each injection) |
| Number of Participants With Medically-Attended Adverse Events (MAAEs) | 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) | Day 1 through Month 30 |
| Geometric Mean Titers (GMTs) of Antigen-Specific Neutralizing Antibody (nAb) | Month 30 up to Month 54 |
| Geometric Mean Concentration (GMC) of Binding Antibody | Month 30 up to Month 54 |
| Seroconversion From a Negative to a Positive Result for Serum IgG Against Antigens not Encoded by mRNA-1647 | Month 30 up to Month 54 |
| Seroconversion From a Negative to a Positive Result for Serum Immunoglobulin G (IgG) Against Antigens not Encoded by mRNA-1647 | 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) | Up to 176 days (7 days after each injection) |
Secondary
| Measure | Time frame |
|---|---|
| GMC of Antigen-Specific Binding Antibody | Day 1, Months 3, 7, 12, 18, 24, and 30 |
| Number of Participants with AEs leading to Study Discontinuation, SAEs and Deaths | Month 30 up to Month 54 |
| Number of Participants With Systemic Viral Dissemination | Day 1 through Month 30 |
| Number of Participants With Positive Urine CMV Polymerase Chain Reaction (PCR) Results Post Seroconversion | Day 1 through Month 30 |
| Number of Participants With Positive Urine CMV PCR Results Post Seroconversion | Month 30 up to Month 54 |
| GMTs of Antigen-Specific nAb | Day 1, Months 3, 7, 12, 18, 24, and 30 |
Countries
Australia, Belgium, Canada, Estonia, Finland, France, Germany, Israel, Italy, Japan, Spain, United Kingdom, United States
Outcome results
None listed