A Dose Escalation Study to Evaluate Safety, Reactogenicity, and Immunogenicity of mRNA-1345 in Healthy Adults and in Children Who Are Respiratory Syncytial Virus (RSV)-Seropositive

NCT04528719 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: mRNA-1345-P101
• Study Type: interventional
• Target: 651
• Locations: 1 country
• Sites: 31

Brief Summary

The primary objectives of this study are to evaluate the tolerability and reactogenicity of a single injection of up to 5 dose levels of mRNA-1345 in younger adults, women of child-bearing potential, and older adults including Japanese older adults; of 3 injections of the middle dose level of mRNA-1345 given 56 days apart in younger adults; of a booster injection of mRNA-1345 given approximately 12 and 24 months after the primary injection in older adults; and of 3 injections of 1 of 2 dose levels of mRNA-1345 given 56 days apart in children who are RSV-seropositive.

Conditions

Respiratory Syncytial Virus

Keywords

Viral Diseases; Messenger RNA; Moderna; mRNA-1345; Respiratory syncytial virus; RSV Seropositive; Safety; Pediatric; Vaccines

Outcome Measures

Primary Outcomes (3)

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

  Up to Day 737 (7 days after each injection)

• Number of Participants with Unsolicited Adverse Events (AEs)

  Up to Day 758 (28 days after the last injection)

• Number of Participants with Serious AEs or Medically Attended AEs (MAAEs)

  Up to Day 1095 (End of Study)

Secondary Outcomes (3)

• Geometric Mean Titer (GMT) of Serum RSV Neutralizing and Binding Antibodies (Abs)

  Up to Day 141 (Cohorts 5 and 6), up to Day 169 (Cohorts 1, 2, 4, 12, 13, 14, and 15), up to Day 281 (Cohort 3), and up to Day 1095 (Cohorts 7, 8, 9, 10, and 11)

• Geometric Mean Fold-Rise of Postbaseline/Baseline Ab Titers

  Up to Day 141 (Cohorts 5 and 6), up to Day 169 (Cohorts 1, 2, 4, 12, 13, 14, and 15), up to Day 281 (Cohort 3), and up to Day 1095 (Cohorts 7, 8, 9, 10, and 11)

• Proportion of Participants with ≥2-fold and ≥4-fold Increases in Ab Titers from Baseline

  Up to Day 141 (Cohorts 5 and 6), up to Day 169 (Cohorts 1, 2, 4, 12, 13, 14, and 15), up to Day 281 (Cohort 3), and up to Day 1095 (Cohorts 7, 8, 9, 10, and 11)

Study Arms (15)

Cohort 1: Dose A in Younger Adults

EXPERIMENTAL

Single injection of Dose A of mRNA-1345 or matching-placebo on Day 1.

Biological: mRNA-1345; Drug: Placebo

Cohort 2: Dose B in Younger Adults

EXPERIMENTAL

Single injection of Dose B of mRNA-1345 or matching-placebo on Day 1.

Biological: mRNA-1345; Drug: Placebo

Cohort 3: Dose B in Younger Adults

EXPERIMENTAL

Three total injections, 1 injection of either Dose B of mRNA-1345 or matching-placebo per day on Day 1, Day 57, and Day 113.

Biological: mRNA-1345; Drug: Placebo

Cohort 4: Dose C in Younger Adults

EXPERIMENTAL

Single injection of Dose C of mRNA-1345 or matching-placebo on Day 1.

Biological: mRNA-1345; Drug: Placebo

Cohort 5: Dose D in Children

EXPERIMENTAL

Three total injections, 1 injection of either Dose D of mRNA-1345 or matching-placebo per day on Day 1, Day 57, and Day 113.

Biological: mRNA-1345; Drug: Placebo

Cohort 6: Dose G in Children

EXPERIMENTAL

Three total injections, 1 injection of either Dose G of mRNA-1345 or matching-placebo per day on Day 1, Day 57, and Day 113.

Biological: mRNA-1345; Drug: Placebo

Cohort 7: Dose A in Older Adults

EXPERIMENTAL

Two total injections, 1 injection of either Dose A of mRNA-1345 or matching-placebo per day on Day 1 and approximately 12 months later. Participants will receive second booster injection of Dose A of mRNA-1345 at Month 24.

Biological: mRNA-1345; Drug: Placebo

Cohort 8: Dose B in Older Adults

EXPERIMENTAL

Two total injections, 1 injection of either Dose B of mRNA-1345 or matching-placebo per day on Day 1 and approximately 12 months later. Participants will receive second booster injection of Dose A of mRNA-1345 at Month 24.

Biological: mRNA-1345; Drug: Placebo

Cohort 9: Dose C in Older Adults

EXPERIMENTAL

Two total injections, 1 injection of either Dose C of mRNA-1345 or matching-placebo per day on Day 1 and approximately 12 months later. Participants will receive second booster injection of Dose A of mRNA-1345 at Month 24.

Biological: mRNA-1345; Drug: Placebo

Cohort 10: Dose E in Older Adults

EXPERIMENTAL

Two total injections, 1 injection of either Dose E of mRNA-1345 or matching-placebo per day on Day 1 and approximately 12 months later. Participants will receive second booster injection of Dose A of mRNA-1345 at Month 24.

Biological: mRNA-1345; Drug: Placebo

Cohort 11: Dose F in Older Adults

EXPERIMENTAL

Two total injections, 1 injection of either Dose F of mRNA-1345 or matching-placebo per day on Day 1 and approximately 12 months later. Participants will receive second booster injection of Dose A of mRNA-1345 at Month 24.

Biological: mRNA-1345; Drug: Placebo

Cohort 12: Dose E in Women of Child-Bearing Potential

EXPERIMENTAL

Single injection of Dose E of mRNA-1345 or matching-placebo on Day 1.

Biological: mRNA-1345; Drug: Placebo

Cohort 13: Dose F in Women of Child-Bearing Potential

EXPERIMENTAL

Single injection of Dose F of mRNA-1345 or matching-placebo on Day 1.

Biological: mRNA-1345; Drug: Placebo

Cohort 14: Dose A in Women of Child-Bearing Potential

EXPERIMENTAL

Single injection of Dose A of mRNA-1345 or matching-placebo on Day 1.

Biological: mRNA-1345; Drug: Placebo

Cohort 15: Dose B in Japanese Older Adults

EXPERIMENTAL

Single injection of Dose B of mRNA-1345 or matching-placebo on Day 1.

Biological: mRNA-1345; Drug: Placebo

Interventions

mRNA-1345 BIOLOGICAL

Formulation for injection

Cohort 10: Dose E in Older Adults; Cohort 11: Dose F in Older Adults; Cohort 12: Dose E in Women of Child-Bearing Potential; Cohort 13: Dose F in Women of Child-Bearing Potential; Cohort 14: Dose A in Women of Child-Bearing Potential; Cohort 15: Dose B in Japanese Older Adults; Cohort 1: Dose A in Younger Adults; Cohort 2: Dose B in Younger Adults; Cohort 3: Dose B in Younger Adults; Cohort 4: Dose C in Younger Adults; Cohort 5: Dose D in Children; Cohort 6: Dose G in Children; Cohort 7: Dose A in Older Adults; Cohort 8: Dose B in Older Adults; Cohort 9: Dose C in Older Adults

Placebo DRUG

0.9% sodium chloride (normal saline) injection

Cohort 10: Dose E in Older Adults; Cohort 11: Dose F in Older Adults; Cohort 12: Dose E in Women of Child-Bearing Potential; Cohort 13: Dose F in Women of Child-Bearing Potential; Cohort 14: Dose A in Women of Child-Bearing Potential; Cohort 15: Dose B in Japanese Older Adults; Cohort 1: Dose A in Younger Adults; Cohort 2: Dose B in Younger Adults; Cohort 3: Dose B in Younger Adults; Cohort 4: Dose C in Younger Adults; Cohort 5: Dose D in Children; Cohort 6: Dose G in Children; Cohort 7: Dose A in Older Adults; Cohort 8: Dose B in Older Adults; Cohort 9: Dose C in Older Adults

Eligibility Criteria

• Age: 12 Months - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy young adults ≥18 to ≤49 years of age, women of child-bearing potential ≥18 to ≤40 years of age, healthy older adults ≥65 to \<80 years of age, Japanese older adults ≥ 60 years of age, and children ≥12 to \< 60 months of age.
• Willing and physically able to comply with protocol-mandated follow-up, including all procedures.
• Adult participant or parent(s)/legal guardian(s) of pediatric participants has provided written informed consent for participation in this study, including all evaluations and procedures as specified by the protocol.
• Has a body mass index (BMI) from ≥18 kilogram (kg)/meter (m)\^2 to ≤35 kg/m\^2.
• Female participants of non-child-bearing potential. This criterion does not apply for women of child-bearing potential Cohorts 12, 13, and 14.
• Female participants of child-bearing potential may be enrolled in the study, if the participant: 1) has a negative urine pregnancy test at Screening and on the day of vaccination; 2) has practiced adequate contraception or has abstained from all activities that could lead to pregnancy for 28 days prior to vaccination; 3) has agreed to continue adequate contraception through 3 months following the last injection; and 4) is not currently breastfeeding.
• Seropositive for RSV-neutralizing Abs at Screening.
• Has received routine immunizations appropriate for age per local guidance.
• Current height and weight above the third percentile for age.
• Japanese participants are defined as individuals born in Japan, with both parents and 4 grandparents who were born in Japan.

You may not qualify if:

• Has Screening laboratory values Grade ≥1 (younger adult, women of child-bearing potential, and pediatric participants) or \>Grade 1 (older adult participants, including Japanese older adult participants).
• Is acutely ill or febrile on the day of the first injection.
• Has a significant medical history, including but not limited to:
• Congenital or acquired immunodeficiency, including human immunodeficiency virus (HIV) infection.
• Chronic hepatitis or suspected active hepatitis.
• Bleeding disorder that is considered a contraindication to intramuscular (IM) injection or phlebotomy.
• Dermatologic conditions that could affect local solicited AR assessments.
• Any history of allergic or anaphylactic reactions following a vaccination that required medical intervention.
• Autoimmune disease except for Hashimoto's disease.
• Systemic immunosuppressants or immune-modifying drugs for \>14 days in total within 6 months prior to the day of enrollment. Topical tacrolimus is allowed if not used within 14 days prior to the day of enrollment. Inhaled, nasal, and topical steroids are allowed.
• Intravenous blood products (red cells, platelets, and immunoglobulins \[Ig\]) within 3 months prior to enrollment.
• Has received or plans to receive any licensed or authorized vaccine, to include COVID-19 vaccines, ≤ 28 days prior to the first injection (Day 1) or plans to receive a licensed vaccine within 28 days before or after any study vaccine injection, with the exception of licensed influenza vaccines, which may be received more than 14 days before or after any study vaccine injection. Nonstudy vaccinations should not be delayed.
• Has a history of myocarditis, pericarditis, or myopericarditis.
• Known history of poorly controlled hypertension (per determination of the Investigator) or systolic blood pressure \>160 millimeters of mercury (mmHg) at the Screening visit.
• Known history of hypotension or systolic blood pressure \<85 mmHg at the Screening visit.

Sponsors & Collaborators

• ModernaTX, Inc.: lead

Study Sites (31)

Paradigm Clinical Research Institute Inc - ClinEdge - PPDS

La Mesa, California, 91942-3189, United States

Location

Mills Clinical Research

West Hollywood, California, 90046, United States

Location

Accel Research Site - Angel Kids Pediatrics - ERN - PPDS

DeLand, Florida, 32720-0834, United States

Location

Accel Research Sites - Nona Pediatric Center - ERN - PPDS

Orlando, Florida, 32806-2908, United States

Location

Palm Beach Research - ClinEdge - PPDS

West Palm Beach, Florida, 33409-3401, United States

Location

Centricity Research - Roswell - HyperCore - PPDS

Columbus, Georgia, 31904-8946, United States

Location

IResearch Atlanta LLC

Decatur, Georgia, 30030-3438, United States

Location

Velocity Clinical Research (Savannah - Georgia) - PPDS

Savannah, Georgia, 31406-2675, United States

Location

East-West Medical Research Institute

Honolulu, Hawaii, 96814-4526, United States

Location

Synexus - Optimal Research - Peoria

Peoria, Illinois, 61614, United States

Location

Velocity Clinical Research (Sioux City - Iowa) - PPDS

Sioux City, Iowa, 51106-4233, United States

Location

Michael W. Simon, M.D., PSC

Nicholasville, Kentucky, 40517, United States

Location

Velocity Clinical Research (Lafayette - Louisiana) - PPDS

Lafayette, Louisiana, 70508-5173, United States

Location

Velocity Clinical Research (Metaire - Louisiana) - PPDS

Metairie, Louisiana, 70006, United States

Location

Velocity Clinical Research (Slidell - Louisiana) - PPDS

Slidell, Louisiana, 70458-5334, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Alliance for Multispecialty Research - Kansas City

Kansas City, Missouri, 64114-4866, United States

Location

Velocity Clinical Research (Grand Island - Nebraska) - PPDS

Grand Island, Nebraska, 68803, United States

Location

Velocity Clinical Research (Hastings - Nebraska) - PPDS

Hastings, Nebraska, 68901, United States

Location

Velocity Clinical Research (Norfolk - Nebraska) - PPDS

Norfolk, Nebraska, 68701, United States

Location

Velocity Clinical Research (Omaha - Nebraska) - PPDS

Omaha, Nebraska, 68134, United States

Location

Velocity Clinical Research (Albuquerque - New Mexico) - PPDS

Albuquerque, New Mexico, 87102-3876, United States

Location

Velocity Clinical Research (Binghamton - New York) - PPDS

Binghamton, New York, 13901-1046, United States

Location

Velocity Clinical Research - Medford - ERN - PPDS

Medford, Oregon, 97504-9741, United States

Location

Velocity Clinical Research - Columbia - PPDS

Columbia, South Carolina, 29204, United States

Location

Velocity Clinical Research (Greenville - South Carolina) - PPDS

Greenville, South Carolina, 29615-4833, United States

Location

Cyfair Clinical Research Center - ERN - PPDS

Houston, Texas, 77065, United States

Location

Flourish Research - San Antonio - PPDS

San Antonio, Texas, 78229-3539, United States

Location

DM Clinical Research

Tomball, Texas, 77375-6543, United States

Location

Tanner Clinic

Layton, Utah, 84041, United States

Location

Clinical Research Partners LLC

Richmond, Virginia, 23226-3787, United States

Location

Related Publications (4)

• Schnyder Ghamloush S, Fanning S, Essink B, Eder F, Snape MD, Stoszek SK, Guo R, Dhar R, Righi V, Morsy L, Kapoor A, El Asmar L, Shaw CA. Safety and immunogenicity of an mRNA-based RSV vaccine in seropositive children aged 12-59 months. Hum Vaccin Immunother. 2025 Dec;21(1):2557676. doi: 10.1080/21645515.2025.2557676. Epub 2025 Sep 15.

  PMID: 40953212 DERIVED

• Fitz-Patrick D, Mihara H, Mills A, Mithani R, Kapoor A, Dhar R, Wilson L, Guo R, Simorellis AK, Panozzo CA, Reuter C, Wilson E, Chen GL, Stoszek SK, Shaw CA, Goswami J. Safety and immunogenicity of an mRNA-based RSV vaccine in Japanese older adults aged >/=60 years: A phase 1, randomized, observer-blind, placebo-controlled trial. Respir Investig. 2024 Nov;62(6):1037-1043. doi: 10.1016/j.resinv.2024.08.011. Epub 2024 Sep 9.

  PMID: 39255587 DERIVED

• Shaw CA, Essink B, Harper C, Mithani R, Kapoor A, Dhar R, Wilson L, Guo R, Panozzo CA, Wilson E, Simorellis AK, Reuter C, Stoszek SK, Chen GL, Das R, Goswami J. Safety and Immunogenicity of an mRNA-Based RSV Vaccine Including a 12-Month Booster in a Phase 1 Clinical Trial in Healthy Older Adults. J Infect Dis. 2024 Sep 23;230(3):e647-e656. doi: 10.1093/infdis/jiae081.

  PMID: 38385566 DERIVED

• Shaw CA, Mithani R, Kapoor A, Dhar R, Wilson L, El Asmar L, Schnyder-Ghamloush S, Schaefers K, August A, Stoszek SK, Chen GL. Safety, Tolerability, and Immunogenicity of an mRNA-Based Respiratory Syncytial Virus Vaccine in Healthy Young Adults in a Phase 1 Clinical Trial. J Infect Dis. 2024 Sep 23;230(3):e637-e646. doi: 10.1093/infdis/jiae035.

  PMID: 38298125 DERIVED

MeSH Terms

Conditions

Virus Diseases

Interventions

mRNA-1345 respiratory syncytial virus vaccine

Condition Hierarchy (Ancestors)

Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: For older adult Cohorts 7, 8, 9, 10, and 11, the second booster injection on Day 730 (Month 24) will be open-label.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: August 27, 2020
• Study Start: September 30, 2020
• Primary Completion: July 18, 2024
• Study Completion: July 18, 2024
• Last Updated: August 7, 2024

Record last verified: 2024-08

Locations

US (31)