COVID-19: A Phase 2b/3, Randomized, Observer-Blinded, Placebo-Controlled, Multicenter Clinical Study Evaluating the Efficacy and Safety of Investigational SARS-CoV-2 mRNA Vaccine CVnCoV in Adults 18 Years of Age and Older
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- CureVac
- 入组人数
- 39,680
- 试验地点
- 92
- 主要终点
- Number of Participants Who Experienced a Fatal SAE
研究概览
简要总结
The primary objective of the randomized observer-blinded phase 2b/3 part of this trial is to demonstrate the efficacy of a 2-dose schedule of CVnCoV in the prevention of first episodes of virologically-confirmed cases of COVID-19 of any severity in SARS-CoV-2 naïve participants.
详细描述
This clinical trial information was submitted voluntarily under the applicable law and, therefore, certain submission deadlines may not apply. (That is, clinical trial information for this applicable clinical trial was submitted under section 402(j)(4)(A) of the Public Health Service Act and 42 CFR 11.60 and is not subject to the deadlines established by sections 402(j)(2) and (3) of the Public Health Service Act or 42 CFR 11.24 and 11.44.).
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)
盲法说明
The randomized observer-blinded phases of this study are participant and investigator blinded. This is followed by an open-label phase.
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
- •Male or female participants 18 years of age or older.
- •Be willing and able to provide written informed consent prior to initiation of any trial procedures.
- •Expected compliance with protocol procedures and availability for clinical follow-up through the last planned visit.
- •Females of non-childbearing potential defined as follows: surgically sterile (history of bilateral tubal ligation/occlusion, bilateral oophorectomy or hysterectomy) or postmenopausal {defined as amenorrhea for ≥12 consecutive months prior to screening (Day 1) without an alternative medical cause}. A follicle-stimulating hormone (FSH) level may be measured at the discretion of the Investigator to confirm postmenopausal status.
- •Females of childbearing potential: negative pregnancy test (human chorionic gonadotropin [hCG]) within 24 hours prior to each trial vaccination on Day 1 and Day
- •Females of childbearing potential must use highly effective methods of birth control from 2 weeks before the first administration of the trial vaccine until 3 months following the last administration. The following methods of birth control are considered highly effective when used consistently and correctly:
- •Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal);
- •Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable);
- •Intrauterine devices;
- •Intrauterine hormone-releasing systems;
- •Bilateral tubal ligation;
- •Vasectomized or infertile partner;
- •Sexual abstinence {periodic abstinence (e.g., calendar, ovulation, symptothermal and post-ovulation methods) and withdrawal are not acceptable}.
排除标准
- •History of virologically-confirmed COVID-19 illness.
- •For females: pregnancy or lactation.
- •Use of any investigational or non-registered product (vaccine or drug) within 28 days preceding the administration of trial vaccine or planned use during the trial.
- •Receipt of any licensed vaccines within 28 days (for live vaccines) or 14 days (for inactivated or any other vaccines) prior to administration of the first trial vaccine.
- •Prior administration of any investigational SARS-CoV-2 vaccine or another coronavirus (SARS-CoV, Middle East Respiratory Syndrome-CoV) vaccine or planned used during the trial.
- •Any treatment with immunosuppressants or other immune-modifying drugs (including but not limited to anabolic steroids, corticosteroids, biologicals and methotrexate) for > 14 days total within 6 months preceding the administration of trial vaccine or planned use during the trial. For corticosteroid use, this means prednisone or equivalent, 0.5 mg/kg/day for 14 days or more. The use of inhaled, topical, or localized injections of corticosteroids (e.g., for joint pain/inflammation) is permitted.
- •Any medically diagnosed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination including known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); current diagnosis of or treatment for cancer including leukemia, lymphoma, Hodgkin disease, multiple myeloma or generalized malignancy; chronic renal failure or nephrotic syndrome; and receipt of an organ or bone marrow transplant.
- •History of angioedema (hereditary or idiopathic) or history of any anaphylactic reaction.
- •History of potential immune-mediated disease (pIMD).
- •History of allergy to any component of CVnCoV.
- •Administration of immunoglobulins or any blood products within 3 months prior to the administration of trial vaccine or planned receipt during the trial.
- •Participants with a significant acute or chronic medical or psychiatric illness that, in the opinion of the Investigator, precludes trial participation (e.g., may increase the risk of trial participation, render the participant unable to meet the requirements of the trial, or may interfere with the participant's trial evaluations). These include severe and/or uncontrolled cardiovascular disease, gastrointestinal disease, liver disease, renal disease, respiratory disease, endocrine disorder, and neurological and psychiatric illnesses. However, those with controlled and stable cases can be included in the trial.
- •Participants with impaired coagulation or any bleeding disorder in whom an IM injection or a blood draw is contraindicated.
- •Foreseeable non-compliance with the trial procedure as judged by the Investigator.
- •Roll-over Criteria for the Open-label Phase:
- •Participants must have received at least 1 dose of CVnCoV during the randomized observer blinded phase.
- •Participants must provide additional written informed consent to be eligible for the open label phase.
结局指标
主要结局
Number of Participants Who Experienced a Fatal SAE
时间窗: Day 1 to Day 393
A fatal SAE was defined as an SAE that resulted in death. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Number of Participants Who Experienced a First Episode of Virologically-confirmed {Reverse Transcription Polymerase Chain Reaction (RT-PCR) Positive} Case of COVID-19 of Any Severity
时间窗: Day 44 to Day 393
A case of COVID-19 meeting the definition for primary efficacy analysis was defined as follows: * Virologically-confirmed case of COVID-19 (of any severity) defined as a positive SARS-CoV-2 specific RT-PCR test in a person with clinically symptomatic COVID-19. * Symptom onset ≥ 15 days after second trial vaccination. * First episode of virologically-confirmed COVID-19, i.e. the participant must not have had a history of virologically-confirmed COVID-19 illness at enrollment or have had developed a case of virologically-confirmed COVID-19 before 15 days after the second trial vaccination. * Participant was SARS-CoV-2 naïve at baseline and Day 43 (defined as seronegative to N protein in the blood samples collected at baseline and Day 43). * Primary efficacy cases were confirmed by an Adjudication Committee. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Intensity of SAEs as Per Investigator Assessment
时间窗: Day 1 to Day 393
An SAE was defined as any untoward medical occurrence that, at any dose: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of existing hospitalization. * Resulted in persistent disability/incapacity. * Was a congenital anomaly/birth defect in the offspring of the participant. * Was an important medical event. The Investigator made an assessment of intensity of each SAE reported during the trial. Each SAE was graded from Mild (Grade 1) to Severe (Grade 3), where higher grades indicated a worse outcome. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Phase 2b Participants Only: Intensity of Solicited AEs as Per Investigator Assessment
时间窗: Up to 7 days after vaccination (Days 1 to 7 and Days 29 to 36)
Solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) were recorded on the day of vaccination and the following 7 days using an eDiary. The Investigator made an assessment of intensity of each solicited AE reported during the trial. Each solicited AE was graded from Mild (Grade 1) to Severe (Grade 3), where higher grades indicated a worse outcome. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Number of Participants Who Experienced One or More Medically-attended Adverse Events (AE)
时间窗: Day 1 to Day 211
Medically-attended AEs were defined as AEs with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Clinic visits for COVID-19 testing resulting in negative test results were not considered as medically attended visits, if there is no confirmed diagnosis and no prescribed concomitant medication. The Investigator assessed the relationship between trial vaccine and occurrence of each AE. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Number of Participants Who Experienced One or More Serious AE (SAE)
时间窗: Day 1 to Day 393
An SAE was defined as any untoward medical occurrence that, at any dose: * Resulted in death. * Was life-threatening. * Required inpatient hospitalization or prolongation of existing hospitalization. * Resulted in persistent disability/incapacity. * Was a congenital anomaly/birth defect in the offspring of the participant. * Was an important medical event. The Investigator assessed the relationship between trial vaccine and occurrence of each SAE. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Number of Participants Who Experienced One or More Adverse Event of Special Interest (AESI)
时间窗: Day 1 to Day 393
AESIs included: * AEs with a suspected immune-medicated etiology. * Other AEs relevant to SARS-CoV-2 vaccine development or the target disease. The Investigator assessed the relationship between trial vaccine and occurrence of each AESI. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Phase 2b Participants Only: Duration of Solicited AEs
时间窗: Up to 7 days after vaccination (Days 1 to 7 and Days 29 to 36)
Solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) were recorded on the day of vaccination and the following 7 days using an eDiary. Duration is calculated as consecutive days with a respective solicited AE regardless of the grade of the AE. AEs ongoing after Day 8 are included. In each case only the longest consecutive duration is displayed. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Phase 2b Participants Only: Number of Participants Who Experienced One or More Unsolicited AE
时间窗: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
eDiaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants received a prompt (by e.g., a phone call or text message) to verify whether the participants had any health concerns since the last visit. The Investigator assessed the relationship between trial vaccine and each occurrence of each AE. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Phase 2b Participants Only: Intensity of Unsolicited AEs as Per Investigator Assessment
时间窗: Up to 28 days after vaccination (Days 1 to 29 and Days 29 to 57)
eDiaries were used for collection of unsolicited AEs on each vaccination day and the following 28 days. In addition, participants received a prompt (by e.g., a phone call or text message) to verify whether the participants had any health concerns since the last visit. The Investigator made an assessment of intensity of each unsolicited AE reported during the trial. Each unsolicited AE was graded from Mild (Grade 1) to Severe (Grade 3), where higher grades indicated a worse outcome. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Number of Participants Who Experienced One or More AEs Leading to Vaccine Withdrawal or Trial Discontinuation
时间窗: Day 1 to Day 393
Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
Phase 2b Participants Only: Number of Participants Who Experienced One or More Solicited AE
时间窗: Up to 7 days after vaccination (Days 1 to 7 and Days 29 to 36)
Solicited local AEs (injection site pain, redness, swelling, and itching) and solicited systemic AEs (fever, headache, fatigue, chills, myalgia, arthralgia, nausea/vomiting, and diarrhea) were recorded on the day of vaccination and the following 7 days using an eDiary. Participants were censored at the first day after unblinding or at the day after receiving the authorized/licensed vaccine, whichever was earlier.
次要结局
- Number of Participants Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Severe Case of COVID-19(Day 44 to Day 393)
- Number of Participants Aged ≥ 61 Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Case of COVID-19 of Any Severity(Day 44 to Day 393)
- SARS-CoV-2 Receptor Binding Domain (RBD) of Spike (S) Protein Antibody Levels on Days 1, 29, 43, 120 and 211(Days 1 (baseline), 29, 43, 120 and 211)
- Burden of Disease (BoD) Score #1 Based on First Episodes of Virologically-confirmed (RT-PCR Positive) Cases of COVID-19(Day 44 to Day 393)
- Percentage of Participants Seroconverting to SARS-CoV-2 Viral Neutralizing Antibodies on Days 29, 43, 120 and 211(Baseline and Days 29, 43, 120 and 211)
- BoD Score #2 Based on First Episodes of Virologically-confirmed (RT-PCR Positive) Cases of COVID-19(Day 44 to Day 393)
- SARS-CoV-2 Viral Neutralizing Antibody Levels on Days 1, 29, 43, 120 and 211(Days 1 (baseline), 29, 43, 120 and 211)
- Number of Participants Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Moderate to Severe Case of COVID-19(Day 44 to Day 393)
- Number of Participants Who Experienced a First Episode of Virologically-confirmed (RT-PCR Positive) Case of COVID-19 of Any Severity Due to Infection With "Wild Type" and "Alpha" SARS-CoV-2 Strains in SARS-CoV-2 Naïve Participants(Day 44 to Day 393)
- Percentage of Participants Seroconverting to SARS-CoV-2 RBD of S Protein Antibodies on Days 29, 43, 120 and 211(Baseline and Days 29, 43, 120 and 211)