Dose-Finding Trial to Evaluate the Safety and Immunogenicity of Cytomegalovirus (CMV) Vaccine mRNA-1647 in Healthy Adults

NCT04232280 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: mRNA-1647-P202
• Study Type: interventional
• Target: 315
• Locations: 1 country
• Sites: 9

Brief Summary

This clinical study will assess the safety and immunogenicity of 3 dose levels of mRNA-1647 cytomegalovirus vaccine in CMV-seronegative and CMV-seropositive healthy adults 18-40 years of age.

Conditions

Cytomegalovirus Infection

Keywords

Moderna; mRNA-1647; Cytomegalovirus; CMV; Cytomegalovirus Vaccine; Cytomegalovirus Infections; Cytomegalovirus Congenital; Virus Diseases; Infection Viral; DNA Virus Infections; Messenger RNA

Outcome Measures

Primary Outcomes (7)

• Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs)

  Solicited ARs were selected signs and symptoms occurring after vaccination administration during a specified post-vaccination follow-up period. The occurrence and intensity of the selected signs and symptoms was actively solicited from the participant during a specified post-vaccination follow-up period (day of vaccination and 6 subsequent days), using a predefined checklist in the electronic diary. The following local ARs were solicited: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the vaccination arm. The following systemic ARs were solicited: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, fever, and chills. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

  Up to Day 175 (7 days following last dose administration)

• Number of Participants With Unsolicited Adverse Events (AEs)

  An unsolicited AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. The treatment-emergent AEs are defined as any event not present before exposure to study drug or any event already present that worsened in intensity or frequency after exposure. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section."

  Up to Day 196 (28 days following last dose administration)

• Number of Participants With Medically Attended Adverse Events (MAAEs)

  An MAAE is an AE that lead to a visit to a healthcare practitioner (HCP). This would include visits to study clinic for unscheduled assessments (for example, rash assessment, abnormal laboratory follow-up), and visits to HCPs external to the clinical site (for example, urgent care, primary care physician). A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section."

  Up to Day 336 (6 months following last dose administration)

• Number of Participants With Serious Adverse Events (SAEs)

  An SAE was defined as any untoward medical occurrence that, in the view of either the Investigator or the Sponsor, resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization (hospitalization or prolongation of hospitalization in the absence of a precipitating event was not in itself an SAE), resulted in persistent disability/incapacity, was a congenital anomaly/birth defect, or was a medically important event. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section."

  Up to Day 504 (1 year following last dose administration)

• Geometric Mean Titer (GMT) of Serum Neutralizing Anti-CMV Antibodies Against Epithelial Cell Infection and Against Fibroblast Infection

  Blood samples for antibody-mediated immunogenicity (AMI) analysis were collected during protocol-specified study visits. Serological assessment of serum anti-CMV neutralizing antibody titers against epithelial cell infection and fibroblast infection were measured by a neutralization assay. Results are reported as fold dilution (titer). GMT 95% confidence interval (CI) was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.

  Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504

• Geometric Mean Ratio (GMR) of Serum Neutralizing Anti-CMV Antibodies Against Epithelial Cell Infection and Against Fibroblast Infection

  Blood samples for antibody-mediated immunogenicity analysis were collected during protocol-specified study visits. Serological assessment of serum anti-CMV neutralizing antibody titers against epithelial cell infection and fibroblast infection were measured by a neutralization assay. The GMR measures the changes in immunogenicity titers within participants. Results are reported as a ratio (post-baseline/baseline titers). GMR 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.

  Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504

• Percentage of Participants With ≥2-Fold, 3-Fold, and 4-Fold Increases in Neutralizing Antibodies (nAb) Over Baseline Against Epithelial Cell Infection and Against Fibroblast Infection

  Blood samples for antibody-mediated immunogenicity analysis were collected during protocol-specified study visits. Serological assessment of serum anti-CMV nAb titers against epithelial cell infection and fibroblast infection were measured by a neutralization assay. A ≥z-fold increase from baseline at participant level was defined as a ≥z \* the lower limit of quantification (LLOQ) for participants with baseline antibody level below the LLOQ, or a z-times or higher-level ratio in participants with baseline antibody level equal to or above the LLOQ. LLOQ=16. Results are reported as percentage of participants with ≥2-fold, 3-fold, and 4-fold increases in serum anti-CMV nAb titers from baseline. 95% CI for percentage is calculated using the Clopper-Pearson method.

  Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504

Secondary Outcomes (7)

• GMT of Anti-Glycoprotein B (gB)-Specific Immunoglobulin G (IgG) and Anti-Pentamer-specific IgG as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) of Post-Baseline/Baseline Titers

  Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504

• GMR of Anti-gB-specific IgG and Anti-Pentamer-specific IgG as Measured by ELISA of Post-Baseline/Baseline Titers

  Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504

• GMT of Serum nAb Against Epithelial Cell Infection and Against Fibroblast Infection at Each Timepoint, in the CMV-Seropositive Group and in the CMV-Seronegative Group

  Baseline (Day 1), Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504

• GMR of Serum nAb Against Epithelial Cell Infection and Against Fibroblast Infection at Each Timepoint, in the CMV-Seropositive Group and in the CMV-Seronegative Group

  Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504

• Percentage of Participants With ≥2-Fold, 3-Fold, and 4-Fold Increases Over Baseline of Serum nAb Against Epithelial Cell Infection and Against Fibroblast Infection in the CMV-Seropositive and CMV-Seronegative Groups

  Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504

Study Arms (4)

mRNA-1647 Dose Level A

EXPERIMENTAL

Participants will receive mRNA-1647 vaccine at Dose Level A by intramuscular (IM) injection on Day 1, Day 56, and Day 168.

Biological: mRNA-1647

mRNA-1647 Dose Level B

EXPERIMENTAL

Participants will receive mRNA-1647 vaccine at Dose Level B by IM injection on Day 1, Day 56, and Day 168.

Biological: mRNA-1647

mRNA-1647 Dose Level C

EXPERIMENTAL

Participants will receive mRNA-1647 vaccine at Dose Level C by IM injection on Day 1, Day 56, and Day 168.

Biological: mRNA-1647

Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching to the mRNA-1647 vaccine dose by IM injection on Day 1, Day 56, and Day 168.

Other: Placebo

Interventions

mRNA-1647 BIOLOGICAL

Lyophilized product that is reconstituted with saline then diluted with a special diluent to reach the desired concentration

mRNA-1647 Dose Level A; mRNA-1647 Dose Level B; mRNA-1647 Dose Level C

Placebo OTHER

0.9% sodium chloride (normal saline) injection

Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female 18-40 years of age (Part 1); Female 18-40 years of age (Part 2)
• 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
• Body mass index (BMI) 18-35 kilograms/meter (kg/m\^2)
• Female participants must either be of non-childbearing potential or use acceptable methods of contraception from at least 28 days prior to the first vaccination and through 3 months following last vaccination and is not breastfeeding.
• Male participants must agree to practice adequate contraception from the time of the first vaccination and through 3 months after the last vaccination.

You may not qualify if:

• Acutely ill or febrile on the day of the first vaccination
• Prior receipt of any CMV vaccine
• Abnormal screening safety laboratory test results
• Diagnosis or condition that, in the judgment of Investigator, is clinically unstable or may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to trial procedures
• Has received or plans to receive a vaccine ≤28 days prior to the first vaccination or plans to receive a non-study vaccine within 28 days prior to or after any study vaccination, except for any licensed influenza vaccine which can be administered \>14 days before or after any study vaccination. COVID-19 vaccines (regardless of manufacturer) may be administered \>7 days but preferably \>14 days before or after any study vaccination, with the intention of prioritizing COVID-19 vaccination over all other considerations.
• Prior receipt of chronic systemic immunosuppressants or immune-modifying drugs
• Receipt of intravenous immunoglobulins or plasma products within 3 months prior to the day of the first study vaccination
• Previous receipt of medications in lipid nanoparticle (LNP) formulation (Part 1 participants only)
• Has donated ≥450 milliliters (mL) of blood products within 28 days of the Screening visit
• Participated in an interventional clinical trial within 28 days prior to the day of enrollment
• Is an immediate family member or household member of trial personnel

Sponsors & Collaborators

• ModernaTX, Inc.: lead

Study Sites (9)

Benchmark Research

Sacramento, California, 95864, United States

Location

Optimal Research

Peoria, Illinois, 61614, United States

Location

Johnson County Clin-Trials

Lenexa, Kansas, 66219, United States

Location

Alliance for Multispecialty Research

Lexington, Kentucky, 40509, United States

Location

Aventiv Research Inc

Columbus, Ohio, 43213-6523, United States

Location

Tekton Research Inc

Austin, Texas, 78745, United States

Location

Crossroads Clinical Research

Victoria, Texas, 77901, United States

Location

Foothill Family Clinic

Salt Lake City, Utah, 84109, United States

Location

Foothill Family Clinic-South Clinic

Salt Lake City, Utah, 84121, United States

Location

Related Publications (1)

• Galiza EP, Khalil A, Heath PT. Update on Vaccines in Antenatal Care. Pediatr Infect Dis J. 2024 Feb 1;43(2):e60-e62. doi: 10.1097/INF.0000000000004183. Epub 2023 Dec 27. No abstract available.

  PMID: 38190492 DERIVED

MeSH Terms

Conditions

Cytomegalovirus Infections; Virus Diseases; DNA Virus Infections

Interventions

mRNA-1647 cytomegalovirus vaccine

Condition Hierarchy (Ancestors)

Herpesviridae Infections; Infections

Results Point of Contact

• Title: Moderna Clinical Trials Support Center
• Organization: ModernaTX, Inc.

clinicaltrials@modernatx.com

1-877-777-7187

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Observer-Blind
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2020
• First Posted: January 18, 2020
• Study Start: January 9, 2020
• Primary Completion: January 4, 2023
• Study Completion: January 4, 2023
• Last Updated: May 5, 2026
• Results First Posted: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)