A Phase 3, Randomized, Stratified, Observer-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA-1273 SARS-CoV-2 Vaccine in Adults Aged 18 Years and Older
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 30,415
- 试验地点
- 188
- 主要终点
- Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose
研究概览
简要总结
The mRNA-1273 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of mRNA-1273 to prevent COVID-19 for up to 2 years after the second dose of mRNA-1273.
详细描述
This is a 3-part Phase 3 study, with Part A (Blinded Phase), Part B (Open-label Observational Phase), and Part C (Booster Dose Phase). Participants in Part A are blinded to their treatment assignment, with participants receiving either mRNA-1273 vaccine or placebo. Part B of the study is designed to offer participants to be unblinded so that participants who received placebo in Part A can request 2 doses of open-label mRNA-1273 vaccine. Additionally, participants who choose to be unblinded and were only able to receive 1 dose of mRNA-1273 due to administrative reasons, can choose to receive the second dose of mRNA-1273 during Part B. In Part C, a booster dose will be provided for all eligible participants who choose to receive one.
Please access www.modernatx.com/cove-study for additional information, such as Study Overview, Participation, and Site Locations along with contact numbers for each location for the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part A is observer-blind. Part B is open-label; participants can request to be unblinded by scheduling a Participant Decision clinic visit. Part C offers participants the option to receive a booster dose for those participants who received at least one dose of mRNA-1273 in the study.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •(Part A only) Participants who are at high risk of SARS-CoV-2 infection, defined as adults whose locations or circumstances put them at appreciable risk of exposure to SARS-CoV-2 and COVID-
- •Understands and agrees to comply with the study procedures and provides written informed consent.
- •Able to comply with study procedures based on the assessment of the Investigator.
- •Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as surgically sterile (history of bilateral tubal ligation, bilateral oophorectomy, hysterectomy) or postmenopausal (defined as amenorrhea for ≥12 consecutive months prior to Screening without an alternative medical cause). A follicle-stimulating hormone (FSH) level may be measured at the discretion of the Investigator to confirm postmenopausal status.
- •Female participants of childbearing potential may be enrolled in the study if the participant fulfills all the following criteria:
- •Has a negative pregnancy test at Screening and on the day of the first dose (Day 1, open-label Day 1, and booster dose Day 1).
- •Has practiced adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to the first dose (Day 1).
- •Has agreed to continue adequate contraception through 3 months following the last dose (Day 29, open-label Day 29, and booster dose Day 1).
- •Is not currently breastfeeding.
- •Healthy adults or adults with pre-existing medical conditions who are in stable condition. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrollment.
- •(Part C Only) Is currently enrolled in Part B of the current study (mRNA-1273-P301).
- •(Part C Only) Has received at least 1 dose of mRNA-1273 in the current study (mRNA-1273-P301).
排除标准
- •Is acutely ill or febrile 72 hours prior to or at Screening or dosing (Part B and Part C). Fever is defined as a body temperature ≥38.0°Celsius/100.4°Fahrenheit. Participants meeting this criterion may be rescheduled within the relevant window periods. Afebrile participants with minor illnesses can be enrolled/dosed at the discretion of the Investigator.
- •Is pregnant or breastfeeding.
- •(Part A Only) Known history of SARS-CoV-2 infection.
- •Prior (Part A) or concurrent (Part B and Part C) administration of non-study coronavirus (SARS-CoV, Middle East Respiratory Syndrome [MERS]-CoV) vaccine or current/planned simultaneous participation in another interventional study to prevent or treat COVID-
- •(Part A Only) Demonstrated inability to comply with the study procedures.
- •An immediate family member or household member of this study's personnel.
- •Known or suspected allergy or history of anaphylaxis, urticaria, or other significant adverse reaction to the vaccine or its excipients.
- •Bleeding disorder considered a contraindication to intramuscular injection or phlebotomy.
- •Has received or plans to receive a vaccine within 28 days prior to the first dose (Day 1) or plans to receive a non-study vaccine within 28 days prior to or after any dose of investigational product (IP) (except for seasonal influenza vaccine).
- •(Part A only) Has participated in an interventional clinical study within 28 days prior to the day of enrollment.
- •Immunosuppressive or immunodeficient state, including human immunodeficiency virus (HIV) infection, asplenia, and recurrent severe infections.
- •Has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to IP dose administration (for corticosteroids ≥20 milligram (mg)/day of prednisone equivalent).
- •Has received systemic immunoglobulins or blood products within 3 months prior to the day of IP dose administration.
- •Has donated ≥450 milliliters (mL) of blood products within 28 days prior to IP dose administration.
研究组 & 干预措施
mRNA-1273
Part A (Blinded): Participants will receive 1 intramuscular (IM) injection of 100 microgram (μg) mRNA-1273 on Day 1 and on Day 29.
Part B (Open-label): Participants who receive mRNA-1273-matching placebo during Part A and choose to be unblinded by participating in Part B, will receive 1 IM injection of 100 μg mRNA-1273 on Day 1 and Day 29. Participants who are only able to receive 1 dose of mRNA-1273 due to administrative reasons, will receive 1 IM injection of 100 μg mRNA-1273 on Day 1, if the participant chooses.
Part C: Eligible participants in Part B who choose to receive booster dose of mRNA-1273, will receive 1 IM injection of 50 μg mRNA-1273 on Day 1.
干预措施: Placebo (Biological)
Placebo
Part A only: Participants will receive 1 IM injection of mRNA-1273-matching placebo on Day 1 and on Day 29, if the participant chooses.
干预措施: Placebo (Biological)
结局指标
主要结局
Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After First Dose
时间窗: up to Day 7 (7 days after first dose)
Solicited ARs (local and systemic) were collected in electronic diary (eDiary) within 7 days of dosing. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. Severity grading for solicited ARs is based on modified Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials. Severity was graded 0-4; a lower score indicated lower severity and a higher score indicated greater severity. The Investigator determined if solicited AR was also to be recorded as an AE. Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is in Reported "Adverse Events" section.
Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose
时间窗: From Day 43 (14 days after second dose) up to approximately 7 months after the second dose
COVID-19 cases were defined as participants meeting clinical criteria based both on symptoms for COVID-19 and on RT-PCR detection of SARS-CoV-2 from samples collected within 72 hours of the study participant reporting symptoms that met the definition of COVID-19. An adjudication committee was assembled for the purpose of reviewing potential cases to determine if the criteria for COVID-19 were met.
Parts A and B: Number of Participants With Serious AEs (SAEs)
时间窗: Day 1 (after dosing) through end of study (up to Day 759)
An SAE was defined as any AE that resulted in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.
Parts A and B: Number of Participants With Medically Attended AEs (MAAEs) and AEs Leading to Discontinuation
时间窗: Day 1 (after dosing) through end of study (up to Day 759)
An MAAE is an AE that leads to an unscheduled visit to a healthcare practitioner (HCP). A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section.
Part A: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) After Second Dose
时间窗: Day 29 to Day 35 (from second dose to 7 days after second dose)
Solicited ARs (local and systemic) were collected in eDiary within 7 days of dosing. Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. Severity grading for solicited ARs is based on modified Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventative Vaccine Clinical Trials. Severity was graded 0-4; lower score indicated lower severity and a higher score indicated greater severity. The Investigator determined if solicited AR was also to be recorded as an AE. Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is in Reported "Adverse Events" section
次要结局
- Parts A and B: Number of Participants With a First Occurrence of Severe COVID-19 Starting 14 Days After Second Dose(From Day 43 (14 days after second dose) up to approximately 8 months for Part A and from PDV/unblinding (at 4 months) to up to 8 months for Part B)
- Part A: Number of Participants With a Secondary Case Definition of COVID-19 Starting 14 Days After Second Dose(From Day 43 (14 days after second dose) up to approximately 7 months after the second dose)
- Part C: Geometric Mean Concentration (GMC) of SARS-CoV-2 Specific nAb After BD Compared to After Second Dose in Part A Measured by Pseudovirus (VAC62)(Part C BD Day 29 and Part A Day 57)
- Part A: Number of Participants With a First Occurrence of SARS-CoV-2 Infection in the Absence of Symptoms Defining COVID-19 Starting 14 Days After Second Dose(From Day 43 (14 days after second dose) up to approximately 7 months after the second dose)
- Part A: Number of Participants With Unsolicited AEs up to 28 Days After Any Injection Dose(Up to 28 days after any dose)
- Part A: Number of Participants With a First Occurrence of Either COVID-19 or SARS-CoV-2 Infection Regardless of Symptomatology or Severity Starting 14 Days After Second Dose(From Day 43 (14 days after second dose) up to approximately 7 months after the second dose)
- Parts A and B: Number of Participants Who Died Due to a Cause Directly Attributed to a Complication of COVID-19 Starting 14 Days After Second Dose(From Day 43 (14 days after second dose) up to approximately 8 months for Part A and from PDV/unblinding (at 4 months) to up to 8 months for Part B)
- Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After Second Dose Regardless of Evidence of Prior SARS-CoV-2 Infection(From Day 43 (14 days after second dose) up to approximately 7 months after the second dose)
- Part C: GMT of SARS-CoV-2 Specific nAb Measured by Pseudovirus (VAC62)(Pre-booster (Baseline), post-booster Day 29 and post-booster Day 181)
- Part A: Number of Participants With a First Occurrence of COVID-19 Starting 14 Days After First Dose(From 14 days after first dose up to approximately 8 months)
- Part A: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb)(Day 1, Day 29, Day 57)
- Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 After BD Compared to After Second Dose in Part A(Part C BD Day 29 and Part A Day 57)
- Part A: Geometric Mean Fold Rise (GMFR) of SARS-CoV-2 Specific nAb(Day 29, Day 57)
- Part A: Percentage of Participants With Seroresponse Against SARS-CoV-2(Day 29, Day 57)
- Part C: Percentage of Participants With Seroresponse Against SARS-CoV-2 Measured by Pseudovirus (VAC62)(Post-booster Day 29 and post-booster Day 181)