A Safety, Tolerability, and Immunogenicity Study of mRNA-1345 and mRNA-1365 in Participants Aged 5 Months to <24 Months

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Moderna Inc.

Participant type

Pediatric, Healthy volunteers

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

28 May 2024 → 18 Dec 2024

Decision date (initial)

2023-08-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ModernaTX, Inc.

External identifiers

EU CT number

2022-502022-41-00

ClinicalTrials.gov

NCT05743881

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others

To evaluate the safety and reactogenicity of study injections

Secondary objectives 3

1. To evaluate the occurrence of clinical RSV or hMPV infections in study participants.
2. To evaluate the antibody response to each study injection.
3. To characterize cellular immunogenicity in a subset of participants.

Conditions and MedDRA coding

Acute lower respiratory infection

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Health Products Regulatory Authority, Medicines And Healthcare Products Regulatory Agency, Paul Ehrlich Institute, The Spanish Agency Of Medicines And Medical Devices

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. The participant is male or female, 8 months to <24 months (Part A) or, 5 months to <8 months (Part B), 8 months to <12 months (Part C), or 5 months to <24 months (Part D) of age at the time of randomization (Day 1/Baseline visit), who is in good general health, in the opinion of the Investigator, based on review of medical history and screening physical examination. Common benign infant conditions (eg, mild to moderate GERD or atopic dermatitis not interfering with injection-site assessment) are allowed.
2. In the Investigator’s opinion, the parent(s)/LAR(s) understand and are willing and physically able to comply with protocol-mandated follow up, including all procedures, and provide written informed consent.
3. The participant is growing normally for age in the opinion of the site clinician in the months prior to enrollment.
4. The participant was born at full-term (≥37 weeks gestation) with a minimum birth weight of 2.5 kg.
5. Participant’s parent(s)/LAR(s) must have access to a consistent means of contact either by telephone contact or email/computer.
6. Part C Cohort 7 and Part D Cohorts 11 and 12: participant must have received nirsevimab ≥6 months prior to Day 1 Visit.
7. Part C Cohort 8: participant was eligible at any time since birth, according to national guidelines, to receive nirsevimab prior to Day 1 Visit but did not do so.

Exclusion criteria 11

1. Has a known history of symptomatic RSV (Part A: within 3 months; Part B, Part C, and Part D: since birth) or hMPV infection (Part A: within 3 months; Part B: since birth) prior to administration of the first dose of IP or has a known close contact with anyone with laboratory-confirmed RSV (Parts A, B, C, and D) or hMPV infection (Parts A or B) within 14 days prior to administration of the first dose of IP.
2. Is acutely ill or febrile 24 hours prior to or at the Screening Visit. Fever is defined as a body temperature ≥38.0°C/ ≥100.4°F. Participants who meet this criterion may have visits rescheduled within the relevant study visit windows. Participants who are afebrile with minor illnesses can be enrolled at the discretion of the Investigator.
3. Has previously been administered an investigational or approved vaccine for prevention of RSV (Parts A, B, C, and D) or hMPV (Parts A and B) infection or if the participant’s mother received an investigational or approved vaccine for the prevention of RSV (Part A, B, C, and D) or hMPV (Parts A and B) infection during pregnancy. a. Part D (Cohorts 9 and 10): Use of approved vaccine during pregnancy for the prevention of RSV infection is allowed.
4. Has received investigational or approved agents for prophylaxis against RSV or hMPV (eg, monoclonal antibodies), or is intending to receive these during the course of the study. a. Part C (Cohort 7 only) and Part D (Cohorts 11 and 12 only): Use of nirsevimab ≥6 months before Day 1 Visit is allowed.
5. Has a known hypersensitivity to a component of the vaccine or its excipients. Hypersensitivity includes, but is not limited to, anaphylaxis or immediate allergic reaction of any severity to a previous dose of an mRNA vaccine or any of its components (including polyethylene glycol or immediate allergic reaction of any severity to polysorbate).
6. Has a medical condition that, according to the Investigator’s judgment, may pose additional risk as a result of participation, interfere with safety assessments, or interfere with interpretation of results.
7. Has a history of diagnosis or condition that, in the judgment of the Investigator, may affect study endpoint assessment or compromise participant safety, specifically the following: a. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination. b. Serious chronic illness c. Major congenital defects d. History of any neurological disorders or seizures e. History of or current autoimmune disease f. History of recurrent wheezing (wheezing should have been verified on auscultation by a doctor) g. History of chronic cough (8 weeks or more duration) h. Previous hospitalization for respiratory illnesses i. History of thrombocytopenia j. History of anemia k. Neurological complications following any prior vaccination l. Born to a mother known or suspected to be HIV positive or Hepatitis C positive (no laboratory testing required) m. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required) n. Chronic hepatitis or suspected active hepatitis o. A bleeding disorder that is considered a contraindication to IM injection or phlebotomy p. Dermatologic conditions that could affect local solicited AR assessments q. Family history of congenital or hereditary immunodeficiency
8. Has received the following: a. Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 14 days prior through 7 days after IP administration. b. Systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to the day of enrollment (for corticosteroids, ≥1 mg/kg/day or ≥10 mg/day prednisone equivalent, if participant weighs >10 kg). Participants may have visits rescheduled for enrollment if they no longer meet this criterion within the Screening Visit window. Inhaled, nasal, and topical steroids are allowed. c. Intravenous or subcutaneous blood products (red cells, platelets, immunoglobulins) within 3 months prior to enrollment.
9. Has participated in an interventional clinical study within 28 days prior to the Screening Visit or plans to do so while participating in this study.
10. Is an immediate family member, or household contact, of an employee of the study site or the Sponsor or someone otherwise directly involved with the conduct of the study. As applicable, family members/household contacts of employees of the larger institution or affiliated private practice not part of the study site may be enrolled if the Investigator does not have any influence over their employment status.
11. A child who has been placed under the control or protection of an agency, organization, institution, or entity by the courts, the government, or a government body acting in accordance with powers conferred on them by laws and regulation (eg, foster care). This does not include a child who is adopted or has an appointed legal guardian.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Solicited local and systemic ARs through 7 days after each injection.
2. Unsolicited AEs through 28 days after each injection.
3. MAAEs from Day 1 to EoS.
4. AESIs from Day 1 to EoS.
5. SAEs from Day 1 to EoS.
6. AEs leading to discontinuation from Day 1 to EoS.

Secondary endpoints 5

1. Number and percentage of participants with RTI, LRTI, severe LRTI, very severe LRTI, and hospitalizations associated with RSV or hMPV from Day 1 through EoS.
2. GMT of serum RSV and hMPV neutralizing antibody across prespecified study timepoints. In Part C and Part D, GMT and GMC will be done only for RSV.
3. GMC of serum RSV F and hMPV F– binding antibody across prespecified study timepoints. In Part C and Part D, GMT and GMC will be done only for RSV.
4. GMFR of postbaseline/baseline neutralizing antibody titers and binding antibody concentrations across prespecified study timepoints.
5. Frequency, magnitude, and/or phenotype of vaccine-specific T-cell responses measured by flow cytometry or other methods. Cellular immunogenicity will not be done in Part B and Part D.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Moderna Inc.

Sponsor organisation

Moderna Inc.

Address

325 Binney Street

City

Cambridge

Postcode

02142-1038

Country

United States

Scientific contact point

Organisation

Moderna Therapeutics Inc.

Contact name

Matthew Snape

Public contact point

Organisation

Moderna Therapeutics Inc.

Contact name

Matthew Snape

Third parties 8

Locations

3 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 2 · Art. 38 CTR

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Application history

6 submissions — initial application plus substantial / non-substantial modifications