A Phase 1, Randomized, Observer-blind, Placebo-controlled, Age De-escalation Study of the Safety, Tolerability, and Immunogenicity of mRNA-1345 and mRNA-1365 in Participants Aged 5 months to < 24 months
- Trial ID
- 2022-502022-41-00
- Protocol
- mRNA-1365-P101
- Sponsor
- Moderna Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and reactogenicity of the study injections, which is crucial for determining the tolerability and potential adverse effects of the mRNA-1345 and mRNA-1365 vaccines in participants aged 5 months to less than 24 months. This assessment is clinically relevant as it ensures the vaccines' safety profile is suitable for this vulnerable age group, potentially impacting vaccination strategies for acute lower respiratory infections.
Secondary objectives include: - Evaluating the occurrence of clinical **RSV** or hMPV infections in study participants, which is important for understanding the vaccines' effectiveness in preventing these infections. - Assessing the antibody response to each study injection, providing insights into the immunogenicity and potential protective effects of the vaccines. - Characterizing cellular immunogenicity in a subset of participants, which helps in understanding the cellular immune response elicited by the vaccines.
Participants
The clinical trial involves a total of **442 participants** who are being evaluated for the safety and reactogenicity of study injections related to **acute lower respiratory infection**. The study population includes both male and female subjects, categorized into different age groups: 8 months to less than 24 months (Part A), 5 months to less than 8 months (Part B), 8 months to less than 12 months (Part C), and 5 months to less than 24 months (Part D). Participants are required to be in good general health, as determined by the Investigator through a review of medical history and a screening physical examination. The trial includes infants with common benign conditions such as mild to moderate gastroesophageal reflux disease (GERD) or atopic dermatitis, provided these do not interfere with injection-site assessment. All participants were born at full-term, with a gestational age of at least 37 weeks and a minimum birth weight of 2.5 kg. The trial population was selected based on the ability of the parents or legally authorized representatives to comply with protocol-mandated follow-up and provide informed consent. Additionally, specific cohorts within Parts C and D have criteria related to prior receipt or eligibility for nirsevimab. The study includes a vulnerable population, as it involves infants and young children.
Plans and Procedures
The clinical trial is a **Phase 1**, randomized, observer-blind, placebo-controlled study designed to evaluate the safety, tolerability, and immunogenicity of **mRNA-1345** and **mRNA-1365** in participants aged 5 months to less than 24 months. The trial targets participants with **acute lower respiratory infection** and aims to assess the safety and reactogenicity of the study injections. The trial is structured to include multiple cohorts based on age, with specific inclusion criteria such as being in good general health, having been born at full-term, and having a minimum birth weight of 2.5 kg. The trial is expected to conclude by July 30, 2026, with recruitment having started on June 2, 2023.
Participants will be involved in the study for a duration that includes several key visits. The initial visit is the inclusion (screening) visit, where eligibility is confirmed based on the inclusion criteria. Following this, participants will undergo randomization at the baseline visit (Day 1). Subsequent follow-up visits will be scheduled to monitor the participants for solicited local and systemic adverse reactions through 7 days after each injection, and unsolicited adverse events through 28 days after each injection. The end-of-study visit will mark the conclusion of the participant's involvement, where primary and secondary endpoints such as the number and percentage of participants with respiratory tract infections and the geometric mean titers of serum antibodies will be evaluated.
The expected length of participant involvement varies depending on the cohort and the specific follow-up schedule, but it generally extends from the baseline visit through to the end-of-study visit. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, adverse events leading to discontinuation, or any other medical condition that, in the opinion of the investigator, warrants withdrawal from the study. The trial employs a rigorous methodology to ensure the collection of reliable and valid data, contributing to the understanding of the safety and efficacy of the investigational products in the pediatric population.
Treatment
The clinical trial involves the administration of several treatments, including experimental medications and a placebo. The **experimental medication** mRNA-1365 is a dispersion for injection, developed by MODERNATX, INC. It contains the active substance MRNA-1365-RSV, classified as a nucleic acid. The pharmaceutical form is a dispersion for injection, and it is administered via **intramuscular injection**. This formulation is specifically designed for pediatric use. The dosing schedule and frequency of administration are determined by the study protocol, ensuring participant safety and compliance.
Another **experimental medication** used in the trial is mRNA-1345, also a dispersion for injection from MODERNATX, INC. It contains the active substance MRNA-1345, similarly classified as a nucleic acid. The administration route is intramuscular injection, and it is formulated for pediatric use. The dosing schedule is aligned with the study's objectives to evaluate safety and immunogenicity.
The trial also includes the use of a **placebo**, which is a sodium chloride solution 0.9%. This solution is a chemically derived substance used as a comparator in the study. It is administered via intramuscular injection, serving as a control to assess the effects of the experimental medications. The placebo is labeled according to study-specific requirements to maintain blinding and ensure accurate data collection.
Additionally, the trial involves the use of Nimenrix, a powder and solvent for solution for injection in a pre-filled syringe. This **auxiliary treatment** is a conjugate vaccine targeting meningococcal groups A, C, W-135, and Y. It contains polysaccharides from Neisseria meningitidis groups conjugated to tetanus toxoid carrier proteins. The administration route is intramuscular injection, and it is used to support the study's objectives by providing a standard-of-care reference.
Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The study is designed to evaluate the safety, tolerability, and immunogenicity of the experimental treatments in a controlled and scientifically rigorous manner.
Efficacy
The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the evaluation of solicited local and systemic adverse reactions (ARs) within 7 days post-injection, unsolicited adverse events (AEs) within 28 days post-injection, medically attended adverse events (MAAEs), adverse events of special interest (AESIs), serious adverse events (SAEs), and AEs leading to discontinuation from Day 1 to the end of the study (EoS). These endpoints are designed to monitor the safety and tolerability of the investigational products, **mRNA-1345** and **mRNA-1365**, in the pediatric population aged 5 months to less than 24 months.
Secondary endpoints focus on the immunogenicity of the vaccines. These include the number and percentage of participants experiencing respiratory tract infections (RTI), lower respiratory tract infections (LRTI), severe LRTI, very severe LRTI, and hospitalizations associated with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV) from Day 1 through EoS. Additionally, the geometric mean titer (GMT) of serum RSV and hMPV neutralizing antibodies, as well as the geometric mean concentration (GMC) of serum RSV F and hMPV F-binding antibodies, will be measured across prespecified study timepoints. The geometric mean fold rise (GMFR) of postbaseline/baseline neutralizing antibody titers and binding antibody concentrations will also be evaluated. Furthermore, the frequency, magnitude, and phenotype of vaccine-specific T-cell responses will be assessed using flow cytometry or other methods, although cellular immunogenicity assessments will not be conducted in Part B and Part D of the study.
Inclusion and Exclusion Criteria
Inclusion Criteria
- 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.
- 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.
- The participant is growing normally for age in the opinion of the site clinician in the months prior to enrollment.
- The participant was born at full-term (≥37 weeks gestation) with a minimum birth weight of 2.5 kg.
- Participant’s parent(s)/LAR(s) must have access to a consistent means of contact either by telephone contact or email/computer.
- Part C Cohort 7 and Part D Cohorts 11 and 12: participant must have received nirsevimab ≥6 months prior to Day 1 Visit.
- 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
- 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.
- 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.
- 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.
- 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.
- 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).
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Latvia | Not Recruiting | 02 Jun 2023 | 100 |
 Poland | Not Recruiting | 02 Jun 2023 | 48 |
 Spain | Not Recruiting | 02 Jun 2023 | 100 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Nimenrix powder and solvent for solution for injection in pre-filled syringe Meningococcal groups A, C, W-135 and Y conjugate vaccine | Placebo | POWDER AND SOLVENT FOR SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | INTRAMUSCULAR INJECTION | — | — | PRD6532973 |
mRNA-1365 | Test | DISPERSION FOR INJECTION | INTRAMUSCULAR INJECTION | — | — | PRD10115337 |
mRNA-1345 | Test | DISPERSION FOR INJECTION | INTRAMUSCULAR INJECTION | — | — | PRD10115114 |
SODIUM CHLORIDE SOLUTION 0.9% | Other | — | INTRAMUSCULAR INJECTION | — | — | SUB20079 |
SODIUM CHLORIDE SOLUTION 0.9% | Placebo | — | INTRAMUSCULAR INJECTION | — | — | SUB20079 |