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

A Phase 2, Randomized, Observer-Blind, Placebo-Controlled, Dose-Finding Trial to Evaluate the Safety and Immunogenicity of Cytomegalovirus Vaccine mRNA-1647 in Healthy Adults

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus Infection
• Intervention / Treatment: Biological: mRNA-1647; Other: Placebo

Detailed Description

mRNA-1647-P202 is a 2-part study. Part 1 of the study evaluates the safety and immunogenicity of 3 dose levels of mRNA-1647 vaccine or placebo, administered on a 0, 2, 6-month schedule in healthy CMV-seronegative and CMV-seropositive males and females, 18 to 40 years of age. A planned interim analysis of safety and immunogenicity through Month 3 (1 month after the second dose) of Part 1 of the study informed the selection of the middle dose level for further development. Part 2 of the study is designed to further evaluate the safety and immunogenicity of the middle dose level of mRNA-1647 vaccine or placebo on a 0, 2, 6-month schedule in approximately 200 healthy participants 18 to 40 years of age, comprised of CMV-seronegative and CMV-seropositive female population, which includes the target population for the pivotal Phase 3 efficacy trial.

• Study Type: Interventional
• Enrollment (Actual): 315
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95864
      • Benchmark Research
  • Illinois
    • Peoria, Illinois, United States, 61614
      • Optimal Research
  • Kansas
    • Lenexa, Kansas, United States, 66219
      • Johnson County Clin-Trials
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Alliance for Multispecialty Research
  • Ohio
    • Columbus, Ohio, United States, 43213-6523
      • Aventiv Research Inc
  • Texas
    • Austin, Texas, United States, 78745
      • Tekton Research Inc
    • Victoria, Texas, United States, 77901
      • Crossroads Clinical Research
  • Utah
    • Salt Lake City, Utah, United States, 84109
      • Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121
      • Foothill Family Clinic-South Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive placebo matching to the mRNA-1647 vaccine dose by IM injection on Day 1, Day 56, and Day 168.	Other: Placebo; 0.9% sodium chloride (normal saline) injection
Experimental: mRNA-1647 Dose Level A; 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; Lyophilized product that is reconstituted with saline then diluted with a special diluent to reach the desired concentration
Experimental: mRNA-1647 Dose Level B; Participants will receive mRNA-1647 vaccine at Dose Level B by IM injection on Day 1, Day 56, and Day 168.	Biological: mRNA-1647; Lyophilized product that is reconstituted with saline then diluted with a special diluent to reach the desired concentration
Experimental: mRNA-1647 Dose Level C; Participants will receive mRNA-1647 vaccine at Dose Level C by IM injection on Day 1, Day 56, and Day 168.	Biological: mRNA-1647; Lyophilized product that is reconstituted with saline then diluted with a special diluent to reach the desired concentration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of Solicited Local and Systemic Adverse Reactions (ARs)	Up to Day 175 (7 days following last dose administration)
Frequency of Unsolicited Adverse Events (AEs)	Up to Day 196 (28 days following last dose administration)
Frequency of Medically-Attended Adverse Events (MAAEs)	Up to Day 336 (6 months following last dose administration)
Frequency of Serious Adverse Events (SAEs)	Up to Day 504 (1 year following last dose administration)
Change from Baseline in Geometric Mean Titer (GMT) of Serum Neutralizing Anti-CMV Antibodies Against Epithelial Cell Infection and Against Fibroblast Infection	Baseline, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
Proportion 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	Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, and Day 504

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in 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
Change from Baseline in Associated GMR of Anti-gB Specific IgG and Anti-Pentamer Specific IgG as Measured by ELISA of Post-Baseline/Baseline Titers	Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
Change from Baseline in 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
Change from Baseline in 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	Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
Proportion of Participants with ≥2-Fold, 3-Fold, and 4-Fold Increases over Baseline of Serum nAb Against Epithelial Cell Infection and Against Fibroblast Infection	Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, and Day 504
Change from Baseline in GMT of Antigen-Specific IgG (ELISA) at each Timepoint in the CMV-Seropositive and CMV-Seronegative Groups	Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504
Change from Baseline in GMR of Antigen-Specific IgG (ELISA) at each Timepoint in the CMV-Seropositive and CMV-Seronegative Groups	Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2020
• Primary Completion (Actual): January 4, 2023
• Study Completion (Actual): January 4, 2023

Study Registration Dates

• First Submitted: January 9, 2020
• First Submitted That Met QC Criteria: January 14, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): January 3, 2024
• Last Update Submitted That Met QC Criteria: December 29, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Virus Diseases; Moderna; mRNA-1647; Cytomegalovirus; CMV; Cytomegalovirus Vaccine; Cytomegalovirus Infections; Cytomegalovirus Congenital; Infection Viral; Messenger RNA; DNA Virus Infections
• Additional Relevant MeSH Terms: Virus Diseases; DNA Virus Infections; Herpesviridae Infections; Infections; Cytomegalovirus Infections
• Other Study ID Numbers: mRNA-1647-P202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No