A Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1468 in Healthy Adults ≥50 Years of Age

Study Overview
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Brief Summary
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The main purpose of this first-in-human study is to generate sufficient safety and immunogenicity data to enable the selection of an appropriate dose level for the initiation of a Phase 2/3 study.

Official Title
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A Phase 1/2, Randomized, Observer-Blind, Active-Controlled, Dose-Ranging Study to Evaluate the Safety, Reactogenicity and Immunogenicity of mRNA-1468, a Candidate Vaccine to Prevent Herpes Zoster (HZ) in Healthy Adults ≥50 Years of Age

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: mRNA-1468
* Biological: Placebo
* Biological: Shingrix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a body mass index of 18 to <40 kilograms/meter squared at the Screening Visit. Females of childbearing potential: have a negative pregnancy test at the Screening Visit and on the day of the first vaccination (Day 1); have practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1; have agreed to continue adequate contraception through 3 months following vaccine administration; are not currently breastfeeding. Exclusion Criteria: Has a history of HZ within the past 10 years. Has been previously vaccinated against varicella or HZ. Is acutely ill or febrile Body temperature ≥38.0°Celsius/100.4°Fahrenheit 72 hours prior to or at the Screening Visit or on Day 1. Participants meeting this criterion may be rescheduled within the allowed window. Has a current or previous diagnosis of congenital or acquired immunodeficiency, immunocompromising/immunosuppressive condition, asplenia, or recurrent severe infections. Certain immune-mediated conditions that are well controlled and stable (for example, Hashimoto thyroiditis) as well as those that do not require systemic immunosuppressive therapy (for example, asthma, psoriasis, or vitiligo) may be permitted at the discretion of the Investigator. Has a dermatologic condition that could affect local solicited adverse reaction assessments (for example, tattoos, psoriasis patches affecting skin over the deltoid areas). Has 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. Has a history of myocarditis, pericarditis, or myopericarditis. Has a reported history of anaphylaxis or severe hypersensitivity reaction after receipt of any mRNA vaccine(s) or any components of the mRNA vaccines. Has received systemic immunosuppressants for >14 days in total within 180 days prior to Screening Visit (for corticosteroids ≥10 milligrams/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study. Inhaled, nasal, intra-articular and topical steroids are allowed. Has received systemic immunoglobulins, long-acting biological therapies that affect immune responses (for example, Infliximab) or blood products within 90 days prior to the Screening Visit or plans to receive them during the study. Other protocol-defined inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 50 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: mRNA-1468: Dose 1<br>Participants will receive placebo by intramuscular (IM) injection on Day 1 followed with mRNA-1468 by IM injection on Day 57. | Biological: mRNA-1468<br>* Sterile liquid dispersion for injection<br>Biological: Placebo<br>* Sterile liquid for injection<br>* Other names: Saline;|
| Experimental: mRNA-1468: Dose 2<br>Participants will receive mRNA-1468 by IM injection on Day 1 and Day 57. | Biological: mRNA-1468<br>* Sterile liquid dispersion for injection<br>|
| Experimental: mRNA-1468: Dose 3<br>Participants will receive mRNA-1468 by IM injection on Day 1 and Day 57. | Biological: mRNA-1468<br>* Sterile liquid dispersion for injection<br>|
| Experimental: mRNA-1468: Dose 4<br>Participants will receive mRNA-1468 by IM injection on Day 1 and Day 57. | Biological: mRNA-1468<br>* Sterile liquid dispersion for injection<br>|
| Active Comparator: Shingrix<br>Participants will receive Shingrix by IM injection on Day 1 and Day 57. | Biological: Shingrix<br>* Sterile suspension for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions |  | Up to Day 64 (7 days after each injection) | 
| Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 85 (28 days after each injection) | 
| Number of Participants with Serious AEs, Medically Attended AEs, AEs Leading to Discontinuation of Study Vaccine or Withdrawal From the Study, and AEs of Special Interest |  | Up to Day 393 (Month 14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer of Anti-glycoprotein E (gE)-specific Binding Antibodies (bAb) as Measured by Enzyme-linked Immunosorbent Assay |  | Day 85 (1 month after injection) | 
| Change from Baseline in Geometric Mean Fold Rise of Anti-gE-specific bAb Titer |  | Baseline, Day 85 and Day 225 (1 and 6 months after each injection) | 
| Vaccine Seroresponse Rate of Participants | Vaccine seroresponse will be defined as an anti-gE-specific bAb titer ≥4-fold if baseline bAb titer is above the lower limit of quantification (LLOQ) or ≥4 * LLOQ if baseline bAb titer is <LLOQ prior to vaccination. | Day 85 and Day 225 (6 months after each injection) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-1468, Herpes Zoster vaccine, Moderna