Clinical trial NCT05137236: A Study to Evaluate the Immunogenicity and Safety of mRNA-1283 COVID-19 Vaccine Boosters
Official title: A Phase 2A, Randomized, Stratified, Observer-Blind Study to Evaluate the Immunogenicity and Safety of mRNA-1283 Vaccine Boosters for SARS-CoV-2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: SARS-CoV-2
Keywords: mRNA-1273
mRNA-1273 vaccine
SARS-CoV-2
SARS-CoV-2 Vaccine
Coronavirus
Virus Diseases
Messenger RNA
COVID-19
COVID-19 Vaccine
Moderna
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2021-11-30
Enrollment: 540
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Parts A and B: Number of Participants with Solicited Local and Systemic Reactogenicity Adverse Reactions (ARs)
timeFrame: Up to Day 7 (7-day follow-up after vaccination)
measure: Parts A and B: Number of Participants with Unsolicited Adverse Events (AEs)
timeFrame: Up to Day 28 (28-day follow-up after vaccination)
measure: 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)
timeFrame: Day 1 to end of study (EOS) (Day 366)
measure: 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
timeFrame: Day 29
measure: 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
timeFrame: Day 29
measure: Part B: GMT of SARS-CoV-2 Specific nAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Day 29
timeFrame: Day 29
measure: Part B: GMT of SARS-CoV-2 Specific bAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Day 29
timeFrame: Day 29
measure: 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
timeFrame: Day 29
measure: 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
timeFrame: Day 29
measure: Part B: GMFR of SARS-CoV-2 Specific nAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Day 29
timeFrame: Day 29
measure: Part B: GMFR of SARS-CoV-2 Specific bAb Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Day 29
timeFrame: Day 29
measure: 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
timeFrame: Day 29
measure: Part B: Number of Participants With Seroresponse Against SARS-CoV-2 Omicron Variant (B.1.1.529) at Day 29
timeFrame: Day 29
Secondary outcomes:
measure: 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
timeFrame: Days 1, 15, 29, 90, 181, and 366
measure: 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
timeFrame: Days 1, 15, 29, 90, 181, and 366
measure: 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
timeFrame: Days 1, 15, 29, 90, 181, and 366
measure: 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
timeFrame: Days 1, 15, 29, 90, 181, and 366
measure: 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
timeFrame: Days 1, 15, 29, 90, 181, and 366
measure: 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
timeFrame: Days 1, 15, 29, 90, 181, and 366
measure: 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
timeFrame: Days 1, 15, 29, 90, 181, and 366
measure: 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
timeFrame: Days 1, 15, 29, 90, 181, and 366
measure: 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
timeFrame: Days 1, 15, 29, 90, 181, and 366
measure: 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
timeFrame: Days 1, 15, 29, 90, 181, and 366
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: MedPharmics, LLC
state: Arizona
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Sunrise
country: United States
facility: Precision Clinical Research
state: Florida
city: Chamblee
country: United States
facility: Tekton Research
state: Georgia
city: Metairie
country: United States
facility: MedPharmics
state: Louisiana
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Clinical Research Institute, Inc - CRN
state: Minnesota
city: Lincoln
country: United States
facility: Meridian Clinical Research (Nebraska)
state: Nebraska
city: Albuquerque
country: United States
facility: MedPharmics, LLC. - Albuquerque
state: New Mexico
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.
state: New York
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Cincinnati
country: United States
facility: Meridian Clinical Research (Cincinnati)
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research Inc
state: Ohio
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Frisco
country: United States
facility: ACRC Trials
state: Texas
city: Houston
country: United States
facility: Ventavia Research Group
state: Texas
city: Newport News
country: United States
facility: Health Research of Hampton Roads Inc.
state: Virginia
Study officials:
References:
citation: Stewart-Jones GBE, Elbashir SM, Wu K, Lee D, Renzi I, Ying B, Koch M, Sein CE, Choi A, Whitener B, Garcia-Dominguez D, Henry C, Woods A, Ma L, Montes Berrueta D, Avena LE, Quinones J, Falcone S, Hsiao CJ, Scheaffer SM, Thackray LB, White P, Diamond MS, Edwards DK, Carfi A. Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains. bioRxiv [Preprint]. 2022 Oct 7:2022.10.07.511319. doi: 10.1101/2022.10.07.511319.