A Study to Evaluate the Immunogenicity and Safety of mRNA-1283 COVID-19 Vaccine Boosters

Study Overview
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Brief Summary
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The main goal of Part A of this study is to assess the safety, reactogenicity, and immunogenicity of the study vaccine candidates. The main goal of Part B of this study is to assess the safety, reactogenicity, and immunogenicity of the mRNA-1283.529 booster vaccine candidate.

Detailed Description
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Part A of this study will assess whether a single dose of mRNA-1283 at three different dose levels or mRNA-1283.211 at two different dose levels will boost antibody responses to the Wuhan-Hu-1 (ancestral strain of SARS-CoV-2) virus, and to the B.1.351 variant, and potentially other SARS-CoV-2 variants, and it will also be used to select a dose for subsequent clinical evaluation. The study will include an active comparator group of participants who will receive mRNA-1273. Participants in Part A who received the primary series of mRNA-1273 with appropriate documentation at least 6 months prior will be randomized 1:1:1:1:1:1 to receive a single boost of mRNA-1283 at one of three dose levels, a single boost of mRNA-1283.211 at one of two dose levels, or a single dose of the active comparator, mRNA-1273. Part B of this study will assess whether a single dose of mRNA-1283.529 at two different dose levels as the second booster after a first booster of mRNA- 1273, at least 3 months prior, will boost antibody response to the ancestral strain of the SARS-CoV-2 virus, the B.1.1.529 variant, and potentially other SARS-CoV-2 variants, and inform dose selection for mRNA-1283.529 booster vaccine candidate for subsequent clinical evaluation. Participants in Part B who received the primary series of mRNA 1273 and who received a first booster dose of mRNA-1273 at least 3 months prior will be enrolled in a 1:1 ratio to receive a single boost of mRNA 1283.529 at one of two dose levels.

Official Title
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A Phase 2A, Randomized, Stratified, Observer-Blind Study to Evaluate the Immunogenicity and Safety of mRNA-1283 Vaccine Boosters for SARS-CoV-2

Conditions
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SARS-CoV-2

Intervention / Treatment
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* Biological: mRNA-1283
* Biological: mRNA-1283.211
* Biological: mRNA-1273
* Biological: mRNA-1283.529


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female participants of nonchildbearing potential may be enrolled in the study. Nonchildbearing potential is defined as bilateral tubal ligation >1 year prior to screening, bilateral oophorectomy, hysterectomy, or menopause. Female participants of childbearing potential may be enrolled in the study if the participant has a negative pregnancy test on the day of vaccination (Day 1), practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, agreed to continue adequate contraception through 3 months following the last vaccine administration, and not currently breastfeeding. Participant must have received their second dose of the mRNA-1273 primary series at least 6 months prior to screening and enrollment (Part A) or have received the mRNA-1273 series and an mRNA-1273 booster dose at least 3 months prior to screening and enrollment (Part B). Exclusion Criteria: Had significant exposure to someone with SARS-CoV-2 infection or COVID-19 in the past 14 days, defined by the US Centers for Disease Control and Prevention (CDC) as a close contact of someone who has COVID-19. Is acutely ill or febrile (temperature ≥38.0 degree Celsius [°C]/100.4 degree Fahrenheit [°F]) less than 72 hours prior to or at the screening visit or Day 1. Has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation, or that could interfere with safety assessments or interpretation of results according to the investigator's judgment. Has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to screening (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. Has received or plans to receive any licensed vaccine ≤28 days prior to the injection (Day 1) or plans to receive a licensed vaccine within 28 days before or after the study injection, with the exception of influenza vaccines, which may be given 14 days before or after receipt of a study vaccine. Has received systemic immunoglobulins or blood products within 3 months prior to the screening visit, or plans to receive these during the study. Has donated ≥ 450 milliliters (mL) of blood products within 28 days prior to the screening visit or plans to donate blood products during the study. Plans to participate in an interventional clinical trial of an investigational vaccine or drug while participating in this study. Note: Other inclusion and 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: mRNA-1283 Dose Level 1<br>Participants will receive single intramuscular (IM) injection of mRNA-1283 at Dose Level 1 on Day 1. | Biological: mRNA-1283<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1283 Dose Level 2<br>Participants will receive single IM injection of mRNA-1283 at Dose Level 2 on Day 1. | Biological: mRNA-1283<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1283 Dose Level 3<br>Participants will receive single IM injection of mRNA-1283 at Dose Level 3 on Day 1. | Biological: mRNA-1283<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1283.211 Dose Level 1<br>Participants will receive single IM injection of mRNA-1283.211 at Dose Level 1 on Day 1. | Biological: mRNA-1283.211<br>* Sterile liquid for injection<br>|
| Experimental: Part A: mRNA-1283.211 Dose Level 2<br>Participants will receive single IM injection of mRNA-1283.211 at Dose Level 2 on Day 1. | Biological: mRNA-1283.211<br>* Sterile liquid for injection<br>|
| Active Comparator: Part A: mRNA-1273<br>Participants will receive single IM injection of mRNA-1273 on Day 1. | Biological: mRNA-1273<br>* Sterile liquid for injection<br>|
| Experimental: Part B: mRNA-1283.529 Dose Level 1<br>Participants will receive single IM injection of mRNA-1283.529 as a second booster at Dose Level 1 on Day 1. | Biological: mRNA-1283.529<br>* Sterile liquid for injection<br>|
| Experimental: Part B: mRNA-1283.529 Dose Level 2<br>Participants will receive single IM injection of mRNA-1283.529 as a second booster at Dose Level 2 on Day 1. | Biological: mRNA-1283.529<br>* Sterile liquid for injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts A and B: Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs) |  | Up to Day 7 (7-day follow-up after vaccination) | 
| Parts A and B: Number of Participants with Unsolicited Adverse Events (AEs) |  | Up to Day 28 (28-day follow-up after vaccination) | 
| Parts A and B: Number of Participants with Any Serious AEs (SAEs), Medically Attended AEs (MAAEs), AEs Leading to Withdrawal From Study, and AEs of Special Interest (AESIs) |  | Day 1 to end of study (EOS) (Day 366) | 
| Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) Against Ancestral SARS-CoV-2 and Against SARS-CoV-2 Variants, Including B.1.351 at Day 29 |  | Day 29 | 
| Part A: GMT of SARS-CoV-2 Specific Binding Antibody (bAb) Against Ancestral SARS-CoV-2 and Against SARS-CoV-2 Variants, Including B.1.351 at Day 29 |  | Day 29 | 
| Part B: GMT of SARS-CoV-2 Specific nAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Day 29 |  | Day 29 | 
| Part B: GMT of SARS-CoV-2 Specific bAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Day 29 |  | Day 29 | 
| Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb Against Ancestral SARS-CoV-2 and Against SARS-CoV-2 Variants, Including B.1.351 at Day 29 |  | Day 29 | 
| Part A: GMFR of SARS-CoV-2 Specific bAb Against Ancestral SARS-CoV-2 and Against SARS-CoV-2 Variants, Including B.1.351 at Day 29 |  | Day 29 | 
| Part B: GMFR of SARS-CoV-2 Specific nAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Day 29 |  | Day 29 | 
| Part B: GMFR of SARS-CoV-2 Specific bAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Day 29 |  | Day 29 | 
| Part A: Number of Participants With Seroresponse Against Ancestral SARS-CoV-2 and Against SARS-CoV-2 Variants, Including B.1.351 at Day 29 |  | Day 29 | 
| Part B: Number of Participants With Seroresponse Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Day 29 |  | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: GMT of SARS-CoV-2 Specific nAb Against Ancestral SARS-CoV-2 and Against SARS-CoV-2 Variants, Including B.1.351 at Days 1, 15, 29, 181, and 366 |  | Days 1, 15, 29, 90, 181, and 366 | 
| Part A: GMT of SARS-CoV-2 Specific bAb Against Ancestral SARS-CoV-2 and Against SARS-CoV-2 Variants, Including B.1.351 at Days 1, 15, 29, 181, and 366 |  | Days 1, 15, 29, 90, 181, and 366 | 
| Part B: GMT of SARS-CoV-2 Specific nAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Days 1, 15, 29, 181, and 366 |  | Days 1, 15, 29, 90, 181, and 366 | 
| Part B: GMT of SARS-CoV-2 Specific bAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Days 1, 15, 29, 181, and 366 |  | Days 1, 15, 29, 90, 181, and 366 | 
| Part A: GMFR of SARS-CoV-2 Specific nAb Against Ancestral SARS-CoV-2 and Against SARS-CoV-2 Variants, Including B.1.351 at Days 1, 15, 29, 181, and 366 |  | Days 1, 15, 29, 90, 181, and 366 | 
| Part A: GMFR of SARS-CoV-2 Specific bAb Against Ancestral SARS-CoV-2 and Against SARS-CoV-2 Variants, Including B.1.351 at Days 1, 15, 29, 181, and 366 |  | Days 1, 15, 29, 90, 181, and 366 | 
| Part B: GMFR of SARS-CoV-2 Specific nAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Days 1, 15, 29, 181, and 366 |  | Days 1, 15, 29, 90, 181, and 366 | 
| Part B: GMFR of SARS-CoV-2 Specific bAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Days 1, 15, 29, 181, and 366 |  | Days 1, 15, 29, 90, 181, and 366 | 
| Part A: Number of Participants With Seroresponse Against Ancestral SARS-CoV-2 and Against SARS-CoV-2 Variants, Including B.1.351 at Days 1, 15, 29, 181, and 366 |  | Days 1, 15, 29, 90, 181, and 366 | 
| Part B: Number of Participants With Seroresponse Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Days 1, 15, 29, 181, and 366 |  | Days 1, 15, 29, 90, 181, and 366 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-1273, mRNA-1273 vaccine, SARS-CoV-2, SARS-CoV-2 Vaccine, Coronavirus, Virus Diseases, Messenger RNA, COVID-19, COVID-19 Vaccine, Moderna