Clinical trial NCT04927065: A Study to Evaluate the Immunogenicity and Safety of mRNA Vaccine Boosters for SARS-CoV-2 (COVID-19) Variants
Official title: A Phase 2/3 Study to Evaluate the Immunogenicity and Safety of mRNA Vaccine Boosters for SARS-CoV-2 Variants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SARS-CoV-2
Keywords: mRNA-1273
mRNA-1273 vaccine
mRNA-1273.211
mRNA-1273.617.2
mRNA-1273.213
mRNA-1273.529
mRNA-1273.214
mRNA-1273.815
mRNA-1273.231
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: 2021-06-15
Enrollment: 5161
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Parts A-H: Sequential Part J: Parallel (participants were randomized to receive either mRNA-1273.815 or mRNA-1273.231)
Primary purpose: PREVENTION

Brief summary: This is a study to evaluate the immunogenicity, safety, and reactogenicity of mRNA-1273.211, mRNA-1273, mRNA-1273.617.2, mRNA-1273.213, mRNA-1273.529, mRNA-1273.214, mRNA-1273.222, mRNA-1273.815, and mRNA-1273.231 administered as booster doses.

Detailed description: This clinical study will consist of 9 parts: A (1 and 2), B, C, D, E, F, G, H, and J.

Part A.1 will evaluate 2 dose levels of the mRNA-1273.211 vaccine when administered as a single booster dose to adult participants of the mRNA-1273-P301 (COVE \[NCT04470427\]) study who have previously received 2 doses of mRNA-1273.

Part A.2 will evaluate the immunogenicity, safety, and reactogenicity of the mRNA-1273.214 vaccine candidate when administered as a second booster dose to adult participants of the mRNA-1273-P205 study who have previously received 2 doses of mRNA-1273 as a primary series and a first booster of (50 μg total mRNA content) of the mRNA-1273.211 in Part A.1 of this study.

Part B will evaluate the mRNA-1273 vaccine when administered as a single booster dose to adult participants of the mRNA-1273-P301 (COVE \[NCT04470427\]) study who have previously received 2 doses of mRNA-1273.

Part C will evaluate 2 dose levels of the mRNA-1273.617.2 vaccine when administered as a single booster dose to adult participants of the mRNA-1273-P301 (COVE \[NCT04470427\]) study who have previously received 2 doses of mRNA-1273.

Part D will evaluate 2 dose levels of the mRNA-1273.213 vaccine when administered as a single booster dose to adult participants of the mRNA-1273-P301 (COVE \[NCT04470427\]) study who have previously received 2 doses of mRNA-1273.

Part E will be enrolled at a single clinical study site. Part E will evaluate the mRNA-1273.213 vaccine when administered as a single booster dose to adult participants who have previously received 2 doses of any SARS-CoV-2 mRNA authorized vaccine, including mRNA-1273.

Part F will consist of 2 cohorts: Cohort 1 will consist of adults who have previously received 2 doses of mRNA-1273 as primary series. Cohort 1 will evaluate the mRNA-1273.529 vaccine as a single booster dose. Cohort 2 will consist of adults who have previously received 2 doses of mRNA-1273 as a primary series and a single booster dose of mRNA-1273 in study mRNA-1273-P301 (COVE \[NCT04470427\]) or under the emergency use authorization (EUA). Cohort 2 will evaluate the mRNA-1273.529 and mRNA-1273 vaccines as a single booster dose.

Part G will evaluate the mRNA1273.214 vaccine candidate when administered as a second booster dose to adults who have previously received 2 doses of mRNA-1273 as a primary series and a single booster dose of mRNA-1273.

Part H will evaluate the immunogenicity, safety, and reactogenicity of the mRNA- 1273.222 vaccine candidate when administered as a second booster dose to adults who have previously received 2 doses of mRNA-1273 as a primary series and a single booster dose of mRNA-1273.

Part J will evaluate mRNA-1273.815 and mRNA-1273.231 when administered as a booster dose to adults who previously received a primary series of mRNA vaccine, a first booster dose of a monovalent mRNA vaccine, and a second booster dose of a bivalent mRNA vaccine against SARS-COV-2.

Eligibility criteria: Key Inclusion Criteria:

* For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, agreement to continue adequate contraception or abstinence through 3 months following the vaccination, and not currently breastfeeding.
* Participants must have been either previously enrolled in the mRNA-1273-P301 (COVE) study, must have received 2 doses of mRNA-1273 in that study, with their second dose at least 6 months prior to enrollment in this study (mRNA-1273-P205), and must be currently enrolled and compliant in that study (that is, has not withdrawn or discontinued early); or participant must have received 2 doses of mRNA-1273 under the EUA with their second dose at least 6 months prior to enrollment in mRNA-1273-P205; or have received a 2 dose primary series of mRNA-1273 followed by a 50 μg booster dose of mRNA-1273 in the mRNA-1273-P301 (COVE) study or under EUA at least 3 months prior to enrolment in mRNA-1273-P205; and able to provide proof of vaccination status at the time of screening (Day 1); or for enrollment in Part A.2, participant must be currently enrolled and compliant in Part A.1 of the mRNA 1273 P205 study and must have received their first booster dose of mRNA 1273.211 50 μg; or for enrollment in Part J, participant must meet at least 1 of the following criteria: completed enrollment in Part H of the mRNA-1273-P205 study; or received a 2-dose primary series of mRNA-1273 (100 μg) followed by a 50 μg booster dose of mRNA-1273 in the mRNA-1273-P301 (COVE) study or under EUA, followed by a 50 μg booster dose of mRNA-1273.222 under EUA at least 3 months prior to enrollment in Part J of mRNA-1273-P205; or previously received a 2-dose primary series of mRNA vaccine against SARS-CoV-2 followed by a booster dose of a monovalent mRNA vaccine, followed by a second booster dose of a bivalent mRNA vaccine. Participants in Part J must also provide proof of vaccination status at the time of screening (Day 0 or Day 1).

Key Exclusion Criteria:

* Significant exposure to someone with SARS-CoV-2 infection or COVID-19 in the past 14 days, as defined by the US Centers for Disease Control and Prevention (CDC) as a close contact of someone who has had COVID-19.
* Known history of SARS-CoV-2 infection within 3 months prior to enrollment.
* Is acutely ill or febrile (temperature ≥38.0°Celsius/\[100.4°Fahrenheit\]) less than 72 hours prior to or at the Screening Visit (Day 0) 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.
* Known or suspected allergy or history of anaphylaxis, urticaria, or other significant AR to the vaccine or its excipients.
* Has a documented history of myocarditis or pericarditis within 2 months prior to Screening Visit (Day 0).
* Has received or plans to receive any licensed vaccine ≤28 days prior to the injection (Day 1) or a licensed vaccine within 28 days before or after they 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 (Day 0) or plans for receipt during the study.
* Has donated ≥450 milliliters (mL) of blood products within 28 days prior to the Screening Visit (Day 0) or plans to donate blood products during the study.
* Is currently experiencing an SAE in Study mRNA-1273-P301 (COVE) at the time of screening for this study.

Note: Other inclusion and exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants With Solicited Local and Systemic ARs
timeFrame: 7 days post-vaccination
measure: Number of Participants With Unsolicited AEs
timeFrame: Up to 28 days post-vaccination
measure: Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs), and AEs Leading to Study or Treatment Discontinuation
timeFrame: Day 1 to EOS (Day 366 for Parts A.1, B, C, D, E, and F; and Day 181 for Parts A.2, H, and J)
measure: Geometric Mean Titer (GMT) of Serum Pseudovirus Neutralizing Antibody (nAb) ID50 Titers Against Omicron BA.1 Variant and Ancestral SARS-CoV-2 at Day 29 - mRNA-1273.214 (50 μg) (Part A.2) Compared to mRNA-1273.211 (50 μg) (Part A.1)
timeFrame: Day 29
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant and Ancestral SARS-CoV-2 at Day 181 - mRNA-1273.214 (50 μg) (Part A.2) Compared to mRNA-1273.211 (50 μg) (Part A.1)
timeFrame: Day 181
measure: Seroresponse Rate (SRR) (Based on Pre-vaccination Baseline) For Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant and Ancestral SARS-CoV-2 at Day 29 - mRNA-1273.214 (50 μg) (Part A.2) Compared to mRNA-1273.211 (50 μg) (Part A.1)
timeFrame: Day 29
measure: SRR (Based on Pre-booster Baseline) For Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant and Ancestral SARS-CoV-2 at Day 29 - mRNA-1273.214 (50 μg) (Part A.2) Compared to mRNA-1273.211 (50 μg) (Part A.1)
timeFrame: Day 29
measure: SRR (Based on Pre-vaccination Baseline) For Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant and Ancestral SARS-CoV-2 at Day 181 - mRNA-1273.214 (50 μg) (Part A.2) Compared to mRNA-1273.211 (50 μg) (Part A.1)
timeFrame: Day 181
measure: SRR (Based on Pre-booster Baseline) For Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant and Ancestral SARS-CoV-2 at Day 181 - mRNA-1273.214 (50 μg) (Part A.2) Compared to mRNA-1273.211 (50 μg) (Part A.1)
timeFrame: Day 181
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) at Day 29 - Part F (Cohort 2): mRNA-1273.529 and mRNA-1273
timeFrame: Day 29
measure: SRR (Based on Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) at Day 29 - Part F (Cohort 2): mRNA-1273.529 and mRNA-1273
timeFrame: Day 29
measure: SRR (Based on Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) at Day 29 - Part F (Cohort 2): mRNA-1273.529 and mRNA-1273
timeFrame: Day 29
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) and Ancestral SARS-CoV-2 (D614G) at Day 29 - mRNA-1273.214 (Part G) Compared to mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 29
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) and Ancestral SARS-CoV-2 (D614G) at Day 91 - mRNA-1273.214 (Part G) Compared to mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 91
measure: SRR (Based on the Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) at Day 29 - mRNA-1273.214 (Part G) Compared to mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 29
measure: SRR (Based on the Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) at Day 29 - mRNA-1273.214 (Part G) Compared to mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 29
measure: SRR (Based on the Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) at Day 91 - mRNA-1273.214 (Part G) Compared to mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 91
measure: SRR (Based on the Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) at Day 91 - mRNA-1273.214 (Part G) Compared to mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 91
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against Omicron BA.4/BA.5 Variant and Ancestral SARS-CoV-2 (D614G) at Day 29 - mRNA-1273.222 (Part H) Compared to mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 29
measure: SRR (Based on Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against Omicron BA.4/BA.5 Variant and Ancestral SARS-CoV-2 (D614G) at Day 29 - mRNA-1273.222 (Part H) Compared to mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 29
measure: SRR (Based on Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against Omicron BA.4/BA.5 Variant and Ancestral SARS-CoV-2 (D614G) at Day 29 - mRNA-1273.222 (Part H) Compared to mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 29
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against SARS-CoV-2 XBB.1.5, BA.4/BA.5, and SARS-CoV-2 BQ.1.1 at Day 15 - Part J: mRNA-1273.231 and mRNA-1273.815
timeFrame: Day 15
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against SARS-CoV-2 XBB.1.5, BA.4/BA.5, and SARS-CoV-2 BQ.1.1 at Day 29 - Part J: mRNA-1273.231 and mRNA-1273.815
timeFrame: Day 29
measure: Geometric Mean Fold Rise (GMFR) of Serum Pseudovirus nAb ID50 Titers Against SARS-CoV-2 XBB.1.5, BA.4/BA.5, and SARS-CoV-2 BQ.1.1 at Day 15 - Part J: mRNA-1273.231 and mRNA-1273.815
timeFrame: Day 15
measure: GMFR of Serum Pseudovirus nAb ID50 Titers Against SARS-CoV-2 XBB.1.5, BA.4/BA.5, and SARS-CoV-2 BQ.1.1 at Day 29 - Part J: mRNA-1273.231 and mRNA-1273.815
timeFrame: Day 29
measure: SRR (Based on the Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against BA.4/BA.5 at Day 15 - Part J: mRNA-1273.231 and mRNA-1273.815
timeFrame: Day 15
measure: SRR (Based on the Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against BA.4/BA.5 at Day 15 - Part J: mRNA-1273.231 and mRNA-1273.815
timeFrame: Day 15
measure: SRR (Based on the Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against BA.4/BA.5 at Day 29 - Part J: mRNA-1273.231 and mRNA-1273.815
timeFrame: Day 29
measure: SRR (Based on the Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against BA.4/BA.5 at Day 29 - Part J: mRNA-1273.231 and mRNA-1273.815
timeFrame: Day 29
Secondary outcomes:
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against Ancestral SARS-CoV-2 (D614G) at Day 29 - Part F (Cohort 2): mRNA-1273.529 and mRNA-1273
timeFrame: Day 29
measure: SRR (Based on the Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against Ancestral SARS-CoV-2 (D614G) at Day 29 - Part F (Cohort 2): mRNA-1273.529 and mRNA-1273
timeFrame: Day 29
measure: SRR (Based on the Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against Ancestral SARS-CoV-2 (D614G) at Day 29 - Part F (Cohort 2): mRNA-1273.529 and mRNA-1273
timeFrame: Day 29
measure: SRR (Based on the Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against Ancestral SARS-CoV-2 (D614G) on Days 29, 91, 181, and 366 - mRNA-1273.214 (Part G) and mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Days 29, 91, 181, and 366
measure: SRR (Based on the Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against Ancestral SARS-CoV-2 (D614G) on Days 29, 91, 181, and 366 - mRNA-1273.214 (Part G) and mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Days 29, 91, 181, and 366
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against BA.4/BA.5 at Day 181 - mRNA-1273.222 (Part H)
timeFrame: Day 181
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against Ancestral SARS-CoV-2 (D614G) at Day 181 - mRNA-1273.222 (Part H) and mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 181
measure: SRR (Based on Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against BA.4/BA.5 at Day 181 - mRNA-1273.222 (Part H)
timeFrame: Day 181
measure: SRR (Based on Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against Ancestral SARS-CoV-2 (D614G) at Day 181 - mRNA-1273.222 (Part H) and mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 181
measure: SRR (Based on Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against BA.4/BA.5 at Day 181 - mRNA-1273.222 (Part H)
timeFrame: Day 181
measure: SRR (Based on Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against Ancestral SARS-CoV-2 (D614G) at Day 181 - mRNA-1273.222 (Part H) and mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Day 181
measure: SRR (Based on the Pre-vaccination Baseline) for Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) at Days 181 and 366 - mRNA-1273.214 (Part G) and mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Days 181 and 366
measure: SRR (Based on the Pre-booster Baseline) for Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) at Days 181 and 366 - mRNA-1273.214 (Part G) and mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Days 181 and 366
measure: GMT of Serum Pseudovirus nAb ID50 Titers Against Omicron BA.1 Variant (B.1.1.529) and Ancestral SARS-CoV-2 (D614G) on Days 181 and 366 - mRNA-1273.214 (Part G) and mRNA-1273 (Part F, Cohort 2, 50 μg mRNA-1273)
timeFrame: Days 181 and 366
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Benchmark Research (California)
state: California
city: Hollywood
country: United States
facility: Research Centers of America
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center For Clinical Research
state: Florida
city: Savannah
country: United States
facility: Meridian Clinical Research-(Savannah Georgia)
state: Georgia
city: Sioux City
country: United States
facility: Meridian Clinical Research (Iowa)
state: Iowa
city: Lenexa
country: United States
facility: Johnson County Clinical Trials
state: Kansas
city: Baton Rouge
country: United States
facility: Meridian Clinical Research-(Baton Rouge, Louisiana)
state: Louisiana
city: Metairie
country: United States
facility: Benchmark Research
state: Louisiana
city: Rockville
country: United States
facility: Meridian Clinical Research-(Rockville Maryland)
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington State University
state: Missouri
city: Saint Louis
country: United States
facility: Sundance Clinical Research
state: Missouri
city: Grand Island
country: United States
facility: Meridian Clinical Research (Grand Island, Nebraska)
state: Nebraska
city: Norfolk
country: United States
facility: Meridian Clinical Research (Norfolk-Nebraska)
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research-(Omaha Nebraska)
state: Nebraska
city: New York
country: United States
facility: Meridian Clinical Research, LLC
state: New York
city: Wilmington
country: United States
facility: Trial Management Associates
state: North Carolina
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Austin
country: United States
facility: Benchmark Research - Austin - HyperCore
state: Texas
city: Austin
country: United States
facility: Tekton Research, Inc.
state: Texas
city: Fort Worth
country: United States
facility: Benchmark Research - Fort Worth - HyperCore
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development, Inc.
state: Texas
city: Tomball
country: United States
facility: DM Clinical Research
state: Texas
Study officials:
References:
citation: Chalkias S, Harper C, Vrbicky K, Walsh SR, Essink B, Brosz A, McGhee N, Tomassini JE, Chen X, Chang Y, Sutherland A, Montefiori DC, Girard B, Edwards DK, Feng J, Zhou H, Baden LR, Miller JM, Das R. A Bivalent Omicron-Containing Booster Vaccine against Covid-19. N Engl J Med. 2022 Oct 6;387(14):1279-1291. doi: 10.1056/NEJMoa2208343. Epub 2022 Sep 16.
citation: Chalkias S, Schwartz H, Nestorova B, Feng J, Chang Y, Zhou H, Dutko FJ, Edwards DK, Montefiori D, Pajon R, Leav B, Miller JM, Das R. Safety and Immunogenicity of a 100 mug mRNA-1273 Vaccine Booster for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). medRxiv [Preprint]. 2022 Mar 7:2022.03.04.22271830. doi: 10.1101/2022.03.04.22271830.