Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1403 and mRNA-1405 to Prevent Norovirus Acute Gastroenteritis in Healthy Adults 18 to 80 Years of Age

• ClinicalTrials.gov Identifier: NCT05992935
• Recruitment Status: Recruiting
• First Posted: August 15, 2023
• Sponsor: ModernaTX, Inc.
• Information provided by (Responsible Party): ModernaTX, Inc.

Tracking Information

• First Submitted Date: August 7, 2023
• First Posted Date: August 15, 2023
• Last Update Posted Date: April 29, 2024
• Actual Study Start Date: August 25, 2023
• Estimated Primary Completion Date: May 7, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 26, 2024)

• Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) [ Time Frame: Up to a maximum of Day 36 (7 days after last study injection) ]
• Number of Participants with Unsolicited Adverse Events (AEs) [ Time Frame: Up to a maximum of Day 57 (28 days after last study injection) ]
• Number of Participants with Medically Attended AEs (MAAEs) [ Time Frame: Day 1 up to a maximum of Day 197 ]
• Number of Participants with Any Serious Adverse Events (SAEs), AEs Leading to Withdrawal From Study/Discontinuation of Study Vaccine, and Adverse Events of Special Interest (AESIs) [ Time Frame: Day 1 up to a maximum of Day 365 ]

Original Primary Outcome Measures (submitted: August 7, 2023)

• Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) [ Time Frame: Up to Day 7 after each study intervention ]
• Number of Participants with Unsolicited Adverse Events (AEs) [ Time Frame: Up to 28 days after each vaccination ]
• Number of Participants with Any Serious AEs (SAEs), Medically Attended AEs (MAAEs), AEs Leading to Withdrawal From Study/Discontinuation of Study Vaccine, and AEs of Special Interest (AESIs) [ Time Frame: Day 1 through 6 months after last study intervention (Day 169) ]
• Number of Participants with Any SAEs, AEs Leading to Withdrawal From Study/Discontinuation of Study Vaccine, and AESIs [ Time Frame: Day 1 to end-of study (Day 365) ]
• Number of Participants with Safety Laboratory Abnormalities [ Time Frame: Up to Day 7 after each study intervention ]

Current Secondary Outcome Measures (submitted: April 26, 2024)

• Geometric Mean Titers (GMT) of Histo-Blood Group Antigen (HBGA) Blocking Antibodies Against Vaccine-matched Norovirus (NoV) Genotypes [ Time Frame: Phase 1: Days 1, 29, and 57; Phase 2: Days 1 and 29 ]
• Geometric Mean Fold Rise (GMFR) of HBGA Blocking Antibodies Titers [ Time Frame: Phase 1: Days 1, 29, and 57; Phase 2: Days 1 and 29 ]
• Percentage of Participants with Seroresponse Based on HBGA Blocking Antibody Titers [ Time Frame: Phase 1: Days 29, and 57; Phase 2: Day 29 ]
• Geometric Mean Concentration (GMC) of Binding Antibody (bAb) Against Vaccine-matched NoV Genotypes [ Time Frame: Days 1, 29, and 57 ]
• GMFR of bAb Levels [ Time Frame: Days 1, 29, and 57 ]
• Percentage of Participants with Seroresponse Based on bAb Levels [ Time Frame: Days 29 and 57 ]

Original Secondary Outcome Measures (submitted: August 7, 2023)

• Geometric Mean Titer (GMT) of Histo-Blood Group Antigen (HBGA) Blocking Antibodies Against Vaccine-matched Norovirus (NoV) Genotypes [ Time Frame: Days 1, 29, and 57 ]
• Geometric Mean Fold Rise (GMFR) of HBGA Blocking Antibodies Titers [ Time Frame: Days 1, 29, and 57 ]
• Percentage of Participants with Seroresponse Based on HBGA Blocking Antibody Titer [ Time Frame: Days 29 and 57 ]
• GMT of Binding Antibody (bAb) Against Vaccine-matched NoV Genotypes [ Time Frame: Days 1, 29, and 57 ]
• GMFR of bAb Titers [ Time Frame: Days 1, 29, and 57 ]
• Percentage of Participants with Seroresponse Based on bAb Titer [ Time Frame: Days 29 and 57 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1403 and mRNA-1405 to Prevent Norovirus Acute Gastroenteritis in Healthy Adults 18 to 80 Years of Age
• Official Title: A Phase 1/2, Randomized, Placebo-Controlled, Observer-Blind, Dose-Ranging Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1403 and mRNA-1405, Multivalent Candidate Vaccines to Prevent Norovirus Acute Gastroenteritis in Healthy Adults 18 to 80 Years of Age
• Brief Summary: The purpose of the Phase 1 Part of this study is to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1403 and mRNA-1405 in healthy adult participants 18 to 49 years of age and 60 to 80 years of age. The purpose of the Phase 2 Part of the study is to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1403 in healthy adult participants 18 to 80 years of age.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Norovirus Acute Gastroenteritis

Intervention

• Biological: mRNA-1403
  Sterile liquid for injection
• Biological: mRNA-1405
  Sterile liquid for injection
• Biological: Placebo
  0.9% sodium chloride (normal saline) injection

Study Arms

• Experimental: Phase 1 Part: mRNA-1403 Dose Level 1
  Participants will receive 2 intramuscular (IM) injections of mRNA-1403 at Dose Level 1.
  Intervention: Biological: mRNA-1403
• Experimental: Phase 1 Part: mRNA-1403 Dose Level 2
  Participants will receive 2 IM injections of mRNA-1403 at Dose Level 2.
  Intervention: Biological: mRNA-1403
• Experimental: Phase 1 Part: mRNA-1403 Dose Level 3
  Participants will receive 2 IM injections of mRNA-1403 at Dose Level 3.
  Intervention: Biological: mRNA-1403
• Experimental: Phase 1 Part: mRNA-1403 Dose Level 4 Regimen 1
  Participants will receive 2 IM injections of mRNA-1403 at Dose Level 4.
  Intervention: Biological: mRNA-1403
• Experimental: Phase 1 Part: mRNA-1403 Dose Level 4 Regimen 2
  Participants will receive 1 IM injection of mRNA-1403 at Dose Level 4 and 1 IM injection of study vaccine-matched placebo.
  Interventions:

  • Biological: mRNA-1403
  • Biological: Placebo
• Experimental: Phase 1 Part: mRNA-1405 Dose Level 1
  Participants will receive 2 IM injections of mRNA-1405 at Dose Level 1.
  Intervention: Biological: mRNA-1405
• Experimental: Phase 1 Part: mRNA-1405 Dose Level 2
  Participants will receive 2 IM injections of mRNA-1405 at Dose Level 2.
  Intervention: Biological: mRNA-1405
• Experimental: Phase 1 Part: mRNA-1405 Dose Level 3
  Participants will receive 2 IM injections of mRNA-1405 at Dose Level 3.
  Intervention: Biological: mRNA-1405
• Experimental: Phase 1 Part: mRNA-1405 Dose Level 4 Regimen 1
  Participants will receive 2 IM injections of mRNA-1405 at Dose Level 4.
  Intervention: Biological: mRNA-1405
• Experimental: Phase 1 Part: mRNA-1405 Dose Level 4 Regimen 2
  Participants will receive 1 IM injections of mRNA-1405 at Dose Level 4 and 1 IM injection of study vaccine-matched placebo.
  Interventions:

  • Biological: mRNA-1405
  • Biological: Placebo
• Placebo Comparator: Phase 1 Part: Placebo
  Participants will receive 2 IM injections of study vaccine-matching placebo.
  Intervention: Biological: Placebo
• Experimental: Phase 2 Part: mRNA-1403 Dose Level 1
  Participants will receive 1 IM injection of mRNA-1403 at Dose Level 1.
  Intervention: Biological: mRNA-1403
• Experimental: Phase 2 Part: mRNA-1403 Dose Level 2
  Participants will receive 1 IM injection of mRNA-1403 at Dose Level 2.
  Intervention: Biological: mRNA-1403
• Experimental: Phase 2 Part: mRNA-1403 Dose Level 3
  Participants will receive 1 IM injection of mRNA-1403 at Dose Level 3.
  Intervention: Biological: mRNA-1403
• Placebo Comparator: Phase 2 Part: Placebo
  Participants will receive 1 IM injection of study vaccine-matching placebo.
  Intervention: Biological: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 26, 2024): 1260
• Original Estimated Enrollment (submitted: August 7, 2023): 660
• Estimated Study Completion Date: May 7, 2025
• Estimated Primary Completion Date: May 7, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Phase 1 Part: Adults 18 to 49 years of age at the time of consent or adults 60 to 80 years of age at the time of consent.
• Phase 2 Part: Adults 18 to 80 years of age at the time of consent.
• Body mass index of 18 to 39 kilogram/meter^2 (inclusive) at the Screening Visit.
• Participants assigned female at birth are eligible to participate if they are not pregnant or breast/chest/body feeding.
• A person of childbearing potential is using a highly effective contraceptive method.
• Participant has provided written informed consent for participation in this study,

Key Exclusion Criteria:

• Is acutely ill or febrile (temperature ≥38.0°C [100.4°F]) 72 hours prior to or at the Screening Visit or Day 1
• 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.
• Has a medical, psychiatric, or occupational condition, including reported history of substance abuse, that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment.
• Has a current or previous diagnosis of immunosuppressive condition, to include human immunodeficiency virus, or immune-mediated (autoimmune) disease that requires immunosuppressive therapies (drugs or biologics). The use of topical corticosteroids or other immunosuppressive agents (for example, topical calcineurin inhibitor) may be eligible for participation at the discretion of the Investigator.
• History of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine or intervention that includes one or more of the same components contained in the study vaccine.
• Any history of myocarditis or pericarditis.
• Coagulopathy or bleeding disorder considered a contraindication to IM injection or phlebotomy.
• Dermatologic conditions that could affect local solicited AR assessments (for example, tattoos, psoriasis patches affecting skin over the deltoid areas).
• Has received systemic immunosuppressive therapies (drugs or biologics) for >14 days in total within 6 months prior to Screening (for corticosteroids ≥10 mg/day of prednisone equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. Inhaled, nasal, intra-articular, and topical steroids are allowed.
• Has received or plans to receive any licensed/authorized vaccine (to include severe acute respiratory syndrome-related coronavirus-2 vaccine) ≤28 days prior to or within 28 days after each study intervention, with the exception of influenza vaccines, which may be given 14 days before or after receipt of a study intervention.
• Has received systemic immunoglobulins or blood products within 3 months prior to the Screening Visit or plans for receipt during the study.
• Has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit or plans to donate blood products during the study.
• Participated in an interventional clinical study within 28 days prior to the Screening Visit based on the medical history interview or plans to participate in an interventional clinical trial of an investigational vaccine or drug while participating in this study.
• Phase 2 Part: Individuals who are participating/have participated in the Phase 1 part of the study are excluded.
• Phase 1 Part: Any individual with laboratory abnormalities achieving thresholds defined in the protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Moderna Clinical Trials Support Center; 1-877-777-7187; clinicaltrials@modernatx.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05992935
• Other Study ID Numbers: mRNA-1403/1405-P101
• Has Data Monitoring Committee: No

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