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

• ClinicalTrials.gov Identifier: NCT04232280
• Recruitment Status: Active, not recruiting
• First Posted: January 18, 2020
• Last Update Posted: December 21, 2021
• Sponsor: ModernaTX, Inc.
• Information provided by (Responsible Party): ModernaTX, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cytomegalovirus Infection	Biological: mRNA-1647; Other: Placebo	Phase 2

Detailed Description:

mRNA-1647-P202 is a 2-part study. Part 1 of the study evaluates the safety and immunogenicity of low, medium, and high 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 315 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Observer-Blind
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: January 9, 2020
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: mRNA-1647 Low Dose; Participants will receive mRNA-1647 vaccine at the Low Dose 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 Medium Dose; Participants will receive mRNA-1647 vaccine at the Medium Dose 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 High Dose; Participants will receive mRNA-1647 vaccine at the High Dose 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
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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. 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 [ Time Frame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 ]
2. 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 [ Time Frame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 ]
3. 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 [ Time Frame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 ]
4. 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 [ Time Frame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 ]
5. 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 [ Time Frame: Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, and Day 504 ]
6. Change from Baseline in GMT of Antigen-Specific IgG (ELISA) at each Timepoint in the CMV-Seropositive and CMV-Seronegative Groups [ Time Frame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 ]
7. Change from Baseline in GMR of Antigen-Specific IgG (ELISA) at each Timepoint in the CMV-Seropositive and CMV-Seronegative Groups [ Time Frame: Baseline, Day 1, Day 29, Day 56, Day 84, Day 168, Day 196, Day 336, Day 504 ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Benchmark Research

Sacramento, California, United States, 95864

United States, Illinois

Optimal Research

Peoria, Illinois, United States, 61614

United States, Kansas

Johnson County Clin-Trials

Lenexa, Kansas, United States, 66219

United States, Kentucky

Alliance for Multispecialty Research

Lexington, Kentucky, United States, 40509

United States, Ohio

Aventiv Research Inc

Columbus, Ohio, United States, 43213-6523

United States, Texas

Tekton Research Inc

Austin, Texas, United States, 78745

Crossroads Clinical Research

Victoria, Texas, United States, 77901

United States, Utah

Foothill Family Clinic

Salt Lake City, Utah, United States, 84109

Foothill Family Clinic-South Clinic

Salt Lake City, Utah, United States, 84121

Sponsors and Collaborators

ModernaTX, Inc.

More Information

• Responsible Party: ModernaTX, Inc.
• ClinicalTrials.gov Identifier: NCT04232280
• Other Study ID Numbers: mRNA-1647-P202
• First Posted: January 18, 2020
• Last Update Posted: December 21, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by ModernaTX, Inc.:

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

Additional relevant MeSH terms:

Infections; Cytomegalovirus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases