A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 31,835
- 试验地点
- 120
- 主要终点
- Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 in Seronegative Participants With Onset at Least 14 Days After the Second Vaccination
研究概览
简要总结
The study will evaluate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed moderate to severe/critical coronavirus disease-2019 (COVID-19), as compared to placebo, in SARS-CoV-2 seronegative adults in the double-blind phase and to describe COVID-19 outcomes, safety, and immunogenicity in the different study cohorts in open-label phase.
详细描述
The aim of the COVID-19 vaccine clinical development program is to develop a safe and effective vaccine for the prevention of COVID-19. Ad26.COV2.S, a COVID-19 vaccine based on a human replication-incompetent Ad26 vector, constructed to encode the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus spike (S) protein, is being developed. The study will consist of: a screening phase (up to 28 days), study period (60-week), and a long-term follow-up period (1 additional year). The total study duration will be maximum 2 years and 3 months for the participants. Assessments for efficacy (COVID-19 signs and symptoms, etc.), immunogenicity (such as humoral immune responses), and safety (such as adverse events [AEs] monitoring) will be performed throughout 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
- Double (Participant, Investigator)
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
- •Contraceptive (birth control) use should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies
- •All participants of childbearing potential must: have a negative highly sensitive urine pregnancy test at screening; and have a negative highly sensitive urine pregnancy test immediately prior to each study vaccine administration
- •Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after receiving the last dose of study vaccine
- •Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study
- •Must be able to read, understand, and complete questionnaires in the electronic clinical outcome assessment (eCOA) (that is, the coronavirus disease-2019 [COVID 19] signs and symptoms surveillance question, the e-Diary, and the electronic patient-reported outcomes (ePROs)
排除标准
- •Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature greater than or equal to (>=) 38.0 degree Celsius (100.4-degree Fahrenheit) within 24 hours prior to the planned first dose of study vaccine; randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor
- •Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients
- •Participant received or plans to receive: (a) licensed live attenuated vaccines - within 28 days before or after planned administration of study vaccine; and (b) other licensed (not live) vaccines - within 14 days before or after planned administration of study vaccine
- •Participant previously received a coronavirus vaccine
- •Participant received an investigational drug within 30 days (including investigational drugs for prophylaxis of COVID-19) or used an invasive investigational medical device within 30 days or received investigational immunoglobulin (Ig) or investigational monoclonal antibodies within 3 months, or received convalescent serum for COVID-19 treatment within 4 months or received an investigational vaccine (including investigational Adenoviral-vectored vaccines) within 6 months before the planned administration of the first dose of study vaccine or is currently enrolled or plans to participate in another investigational study during the course of this study
研究组 & 干预措施
Ad26.COV2.S
Participants will receive intramuscular (IM) injection of Ad26.COV2.S vaccine on Day 1 and Day 57 in the double-blind phase. At unblinding visit (open-label phase), participants who have not yet received second vaccination will receive second dose of Ad26.COV2.S vaccine on Day 57, if applicable and newly enrolled participants will either receive IM injection of one dose of Ad26.COV2.S vaccine on Day 1 or two doses of Ad26.COV2.S vaccine on Day 1 and Day 57. All ongoing participants who only received a single vaccination with Ad26.COV2.S in the study will be offered to receive single booster dose of Ad26.COV2.S in the open label phase preferably within 6 to 12 months after the participant's first Ad26.COV2.S vaccination.
干预措施: Ad26.COV2.S (Biological)
Placebo
Participants will receive IM injection of placebo on Day 1 and Day 57 in the double-blind phase. At unblinding visit (open-label phase), participants initially receiving placebo will be offered to receive IM injection of a single dose of Ad26.COV2.S vaccine. All ongoing participants who only received a single vaccination with Ad26.COV2.S in the study will be offered to receive single booster dose of Ad26.COV2.S in the open label phase preferably within 6 to 12 months after the participant's first Ad26.COV2.S vaccination.
干预措施: Ad26.COV2.S (Biological)
Placebo
Participants will receive IM injection of placebo on Day 1 and Day 57 in the double-blind phase. At unblinding visit (open-label phase), participants initially receiving placebo will be offered to receive IM injection of a single dose of Ad26.COV2.S vaccine. All ongoing participants who only received a single vaccination with Ad26.COV2.S in the study will be offered to receive single booster dose of Ad26.COV2.S in the open label phase preferably within 6 to 12 months after the participant's first Ad26.COV2.S vaccination.
干预措施: Placebo (Other)
结局指标
主要结局
Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 in Seronegative Participants With Onset at Least 14 Days After the Second Vaccination
时间窗: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)
Molecularly confirmed moderate to severe/critical COVID-19 was defined as a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive reverse transcription/polymerase chain reaction (RT-PCR) or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Moderate included one sign or symptom such as respiratory rate \>=20 breaths per minute (min) and symptoms such as shortness of breath or two signs or symptoms such as heart rate \>=90 beats/min and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate \>=30 breaths/min, heart rate \>=125 beats/min, oxygen saturation (SpO2) \<=93 percent (%) on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to Intensive Care Unit (ICU), death defined as per FDA guidance.
次要结局
- Double Blind Phase: Number of Participants With First Occurrence of COVID-19 Requiring Medical Intervention With Onset at Least 14 Days After the Second Vaccination(From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of Serostatus With Onset At Least 1 Day After the First Day 1 Vaccination(From at least 1 day after first vaccination on Day 1 (Day 2) up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of Serostatus With Onset at Least 14 Days After the Second Vaccination(From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 in Seronegative Participants With Onset at Least 1 Day After the First Day 1 Vaccination(From at least 1 day after first vaccination on Day 1 (Day 2) up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 With Onset at Least 14 Days After the First Day 1 Vaccination(From at least 14 days after first vaccination on Day 1 (Day 15) up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 With Onset at Least 28 Days After the First Day 1 Vaccination(From at least 28 days after the first vaccination on Day 1 (Day 29) up to end of double blind phase (7.2 months))
- Double Blind Phase: Area Under the Curve (AUC) of SARS-CoV-2 Viral Load as Assessed by Quantitative RT-PCR in Participants With Molecularly Confirmed Symptomatic COVID-19 With Onset at Least 14 Days After Second Vaccination(From Day 71 up to end of the COVID-19 episode (up to 90 days))
- Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Mild COVID-19 With Onset at Least 14 Days After the Second Vaccination(From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed COVID-19 Defined by the US FDA Harmonized Case Definition With Onset at Least 14 Days After the Second Vaccination(From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With Burden of Disease (BOD) Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19 With Onset at Least 14 Days After the Second Vaccination(From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With Serologic Conversion Between Day 71 up to Unblinding Visit Using an Enzyme-linked Immunosorbent Assay (ELISA)(From Day 71 up to unblinding visit (7.2 months))
- Double Blind Phase: Number of Participants With Asymptomatic Infection Detected By Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) With Onset at Least 14 Days After the Second Vaccination(From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With First Occurrence of SARS-CoV-2 Infection (Serologically and/or Molecularly Confirmed) With Onset at Least 14 Days After the Second Vaccination(From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With Serious Adverse Events (SAEs)(From Day 1 up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With Adverse Events of Special Interest (AESIs)(From Day 1 up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With Medically-Attended Adverse Events (MAAEs)(From Day 1 up to 7.2 months)
- Double-Blind: Number of Participants With MAAEs Leading to Study Discontinuation(From Day 1 up to end of double blind phase (7.2 months))
- Double Blind Phase: Number of Participants With Solicited Local Adverse Events (AEs) During 7 Days Following Each Vaccination(7 days after first vaccination on Day 1 (up to Day 8), 7 days after second vaccination on Day 57 (up to Day 64))
- Double Blind Phase: Number of Participants With Solicited Systemic AEs During 7 Days Following Each Vaccination(7 days after first vaccination on Day 1 (up to Day 8), 7 days after second vaccination on Day 57 (up to Day 64))
- Double Blind Phase: Number of Participants With Unsolicited Adverse Events (AEs) During 28 Days Post Each Vaccination(28 days after first vaccination on Day 1 (up to Day 29), 28 days after second vaccination on Day 57 (up to Day 85))
- Double Blind Phase: SARS-CoV-2 Binding Antibodies Assessed by ELISA(At Baseline (Day 1), Days 29, 57 and 71)