A Study of mRNA-1018 Pandemic Influenza Candidate Vaccines in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this Phase 1/2 study is to generate sufficient safety and immunogenicity data of mRNA-1018 pandemic influenza candidate vaccines in healthy adults ≥18 years of age to enable the initiation of a large Phase 3 trial with one selected vaccine candidate. The study will be conducted in 2 Parts (Part A and Part B) that will enroll and run concurrently. Part A of the study will evaluate 4 vaccine candidates (H5N8, H7N9, H5 only, and H7 only). Part B of the study will evaluate a single vaccine candidate (H5 only-CG).

Official Title
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Phase 1/2, Randomized, Observer-Blind, Parallel, Dose-Ranging Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1018 Pandemic Influenza Candidate Vaccines in Healthy Adults ≥18 Years of Age

Conditions
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Influenza

Intervention / Treatment
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* Biological: mRNA-1018 for H5N8
* Biological: mRNA-1018 for H7N9
* Biological: mRNA-1018 for H5 Only
* Biological: mRNA-1018 for H7 Only
* Biological: mRNA-1018 for H5 Only-CG


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and results of electrocardiogram testing. Body mass index of 18 kilograms (kg)/square meter (m^2) to 39 kg/m^2 (inclusive) at the Screening visit. For female participants of childbearing potential: negative pregnancy test, adequate contraception, and not currently breastfeeding. Key Exclusion Criteria: Participant is acutely ill or febrile (body temperature ≥ 38.0 degrees Celsius [°C]/100.4 degrees Fahrenheit [°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. Any medical, psychiatric, or occupational condition, including reported history of substance abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results. Participant has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 180 days prior to Screening Visit (for corticosteroids ≥10 milligrams [mg]/day of prednisone equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. Participant has received any vaccine authorized or approved by local health agency including mRNA vaccine ≤28 days prior to study intervention (Day 1) or plans to receive a vaccine authorized or approved by local health agency within 28 days before or after the study intervention. Participant has participated in an interventional clinical study within 28 days prior to the Screening visit based on the medical history interview or plans to do so while participating in this study. Other inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A Group 1 Vaccine: mRNA-1018 for H5N8 Dose Level 1<br>Participants will receive mRNA-1018 for H5N8 at dose level 1 by intramuscular (IM) injection on Day 1 and Day 22. | Biological: mRNA-1018 for H5N8<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 1 Vaccine: mRNA-1018 for H5N8 Dose Level 2<br>Participants will receive mRNA-1018 for H5N8 at dose level 2 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H5N8<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 1 Vaccine: mRNA-1018 for H5N8 Dose Level 3<br>Participants will receive mRNA-1018 for H5N8 at dose level 3 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H5N8<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 1 Vaccine: mRNA-1018 for H5 Only Dose Level 1<br>Participants will receive mRNA-1018 for H5 only at dose level 1 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H5 Only<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 1 Vaccine: mRNA-1018 for H5 Only Dose Level 2<br>Participants will receive mRNA-1018 for H5 only at dose level 2 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H5 Only<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 1 Vaccine: mRNA-1018 for H5 Only Dose Level 3<br>Participants will receive mRNA-1018 for H5 only at dose level 3 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H5 Only<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 2 Vaccine: mRNA-1018 for H7N9 Dose Level 1<br>Participants will receive mRNA-1018 for H7N9 at dose level 1 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H7N9<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 2 Vaccine: mRNA-1018 for H7N9 Dose Level 2<br>Participants will receive mRNA-1018 for H7N9 at dose level 2 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H7N9<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 2 Vaccine: mRNA-1018 for H7N9 Dose Level 3<br>Participants will receive mRNA-1018 for H7N9 at dose level 3 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H7N9<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 2 Vaccine: mRNA-1018 for H7 Only Dose Level 1<br>Participants will receive mRNA-1018 for H7 only at dose level 1 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H7 Only<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 2 Vaccine: mRNA-1018 for H7 Only Dose Level 2<br>Participants will receive mRNA-1018 for H7 only at dose level 2 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H7 Only<br>* Sterile liquid for injection<br>|
| Experimental: Part A Group 2 Vaccine: mRNA-1018 for H7 Only Dose Level 3<br>Participants will receive mRNA-1018 for H7 only at dose level 3 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H7 Only<br>* Sterile liquid for injection<br>|
| Experimental: Part B Group 1 Vaccine: mRNA-1018 for H5 Only-CG Dose Level 1<br>Participants will receive mRNA-1018 for H5 Only-CG at dose level 1 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H5 Only-CG<br>* Sterile liquid for injection<br>|
| Experimental: Part B Group 1 Vaccine: mRNA-1018 for H5 Only-CG Dose Level 2<br>Participants will receive mRNA-1018 for H5 Only-CG at dose level 2 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H5 Only-CG<br>* Sterile liquid for injection<br>|
| Experimental: Part B Group 1 Vaccine: mRNA-1018 for H5 Only-CG Dose Level 3<br>Participants will receive mRNA-1018 for H5 Only-CG at dose level 3 by IM injection on Day 1 and Day 22. | Biological: mRNA-1018 for H5 Only-CG<br>* Sterile liquid for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Solicited Local and Systemic Adverse Reactions (ARs) |  | Up to Day 29 (7 days after each injection) | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 43 (21 days after each injection) | 
| Number of Participants with AEs Leading to Discontinuation From Study |  | Day 1 to Day 205 (end of study [EoS]) | 
| Number of Participants with Medically-Attended AEs (MAAEs) |  | Day 1 to Day 205 (EoS) | 
| Number of Participants with Serious Adverse Events (SAEs) |  | Day 1 to Day 205 (EoS) | 
| Number of Participants with Adverse Events of Special Interest (AESIs) |  | Day 1 to Day 205 (EoS) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) of Anti-Hemagglutinin (HA) Antibodies at Days 22, 29, and 43, as Measured by Hemagglutination Inhibition (HAI) Assay |  | Days 22, 29, and 43 | 
| Geometric Mean Fold Rise (GMFR) of Anti-HA Antibodies From Baseline to Days 22, 29, and 43, as Measured by HAI Assay |  | Baseline (Day 1), Days 22, 29, and 43 | 
| Number of Participants With Seroconversion at Days 22, 29, and 43, as Measured by HAI Assay | Seroconversion is defined as a Day 22, 29, or 43 titer ≥1:40 if baseline is <1:10 or a 4-fold or greater rise if baseline is ≥1:10 in anti-HA antibodies measured by HAI assay. | Baseline (Day 1) to Days 22, 29, and 43 | 
| Number of Participants With HAI Titer ≥ 1:40 at Days 22, 29, and 43 |  | Days 22, 29, and 43 | 
| GMT of Anti-Neuraminidase (NA) Antibodies at Days 22, 29, and 43, as Measured by Neuraminidase Inhibition (NAI) Assay |  | Days 22, 29, and 43 | 
| GMFR of Anti-NA Antibodies From Baseline to Days 22, 29, and 43, as Measured by NAI Assay |  | Baseline (Day 1), Days 22, 29, and 43 | 
| Number of Participants with a Change in the Days 22, 29, and 43 NAI Titer of at Least 2-/3-/4-Fold Rise | Number of participants with a change in the Days 22, 29, or 43 NAI titer of at least 2-/3-/4-fold rise, defined as ≥2-/3-/4-fold of the lower level of quantitation (LLOQ) if the Day 1 titer is <LLOQ; or ≥2-/3-/4-fold of the Day 1 titer if the Day 1 titer is ≥LLOQ. | Baseline (Day 1) to Days 22, 29, and 43 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza vaccine, Moderna, mRNA-1018, Virus Diseases, Vaccines, Pandemic influenza