A Randomized, Double-blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Mono and Combination Therapy With Monoclonal Antibodies in Participants With Mild to Moderate COVID-19 Illness (BLAZE-4)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 1,755
- 试验地点
- 138
- 主要终点
- Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Greater Than 5.27
研究概览
简要总结
The purpose of this study is to measure how well monoclonal antibodies work, either alone or in combination, against the virus that causes COVID-19. Study drug(s) will be given to participants with early symptoms of COVID-19. Samples will be taken from the back of the nose to determine how much virus is in the body at various times during the study. Participation could last about 12 or 24 weeks and includes at least 1 visit to the study site, with the remainder of assessments performed in the home, local clinic, or by phone.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Includes open label arms
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For low-risk participant arms 9-11 only: Are greater than or equal to (≥)18 and less than (<)65 years of age at the time of randomization and do not have the risk factors defined in the bullet point directly below
- •For high-risk participant arms 12 and 13 only:
- •- Are ≥18 years of age and satisfy at least one of the following risk factors at the time of screening
- •Are ≥65 years of age
- •Have a body mass index (BMI) ≥ 35
- •Have chronic kidney disease
- •Have type 1 or type 2 diabetes
- •Have immunosuppressive disease
- •Are currently receiving immunosuppressive treatment, or
- •Are ≥55 years of age AND have
- •cardiovascular disease, OR
- •hypertension, OR
- •chronic obstructive pulmonary disease or other chronic respiratory disease
- •For high-risk participant arms 12 and 13 only:
- •Are 12-17 years of age (inclusive) AND satisfy at least one of the following risk factors at the time of screening
- •Have a BMI ≥85th percentile for their age and gender based on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm
- •Have sickle cell disease
- •Have congenital or acquired heart disease
- •Have neurodevelopmental disorders, for example, cerebral palsy
- •Have a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)
- •Have asthma or reactive airway or other chronic respiratory disease that requires daily medication for control
- •Have type 1 or type 2 diabetes
- •Have chronic kidney disease
- •Have immunosuppressive disease, or
- •Are currently receiving immunosuppressive treatment.
- •For high-risk participants arm 14 only:
- •Are ≥12 years of age and satisfy at least one of the following risk factors at the time of screening Are ≥65 years of age
- •Are adults (≥18 years of age) with BMI >25 kg/m2 , or if age 12-17, have BMI ≥85th percentile for their age and gender based on CDC growth charts
- •Have chronic kidney disease
- •Have type 1 or type 2 diabetes
- •Have immunosuppressive disease
- •Are currently receiving immunosuppressive treatment
- •Have cardiovascular disease (including congenital heart disease) or hypertension
- •Have chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension)
- •Have sickle cell disease
- •Have neurodevelopmental disorder (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
- •Have a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation [not related to COVID-19]
- •Are currently not hospitalized
- •Have one or more mild or moderate COVID-19 symptoms: Fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, or shortness of breath with exertion, nasal congestion or runny nose, new loss of smell, chills
- •Must have sample taken for test confirming viral infection no more than 3 days prior to starting the drug infusion
- •Are men or non-pregnant women who agree to contraceptive requirements
- •Understand and agree to comply with planned study procedures
- •Agree to the collection of nasopharyngeal swabs and venous blood
- •The participant or legally authorized representative give signed informed consent and/or assent
排除标准
- •For low-risk participants only: BMI ≥35
- •Have oxygen saturation (SpO2) less than or equal to (≤)93 percent (%) on room air at sea level or ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (FiO2) <300, respiratory rate ≥30 per minute, heart rate ≥125 per minute
- •Require mechanical ventilation or anticipated impending need for mechanical ventilation
- •Have known allergies to any of the components used in the formulation of the interventions
- •Have hemodynamic instability requiring use of pressors within 24 hours of randomization
- •Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking intervention
- •Have any co-morbidity requiring surgery within <7 days, or that is considered life-threatening within 29 days
- •Have any serious concomitant systemic disease, condition or disorder that, in the opinion of the investigator, should preclude participation in this study
- •Have a history of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test prior to the one serving as eligibility for this study
- •Have received an investigational intervention for SARS-CoV-2 prophylaxis within 30 days before dosing
- •Have received treatment with a SARS-CoV-2 specific monoclonal antibody
- •Have a history of convalescent COVID-19 plasma treatment
- •For low-risk arms only: have received a SARS-CoV-2 vaccine or have participated in a previous SARS-CoV-2 vaccine study and are currently blinded to treatment allotment
- •Have participated, within the last 30 days, in a clinical study involving an investigational intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 30 days, whichever is longer, should have passed
- •Are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- •Are pregnant or breast feeding
- •Are investigator site personnel directly affiliated with this study
- •Have body weight <40 kilograms
研究组 & 干预措施
Placebo (Pbo)
Treatment 1: Pbo administered intravenously (IV).
Treatment 8: Pbo For 700 mg Bamlanivimab (BAM) + 500 mg VIR-7831 (Amendment (C-e)) administered IV.
Treatment 11: Pbo For 175 mg Bebtelovimab (BEB) & 700 mg BAM +1400 mg Etesevimab ( ETE) +175 mg BEB (Low Risk Participants) administered IV.
Pooled Placebo (Addendum 4, IV) administered IV.
Pooled Placebo (Addendum 4, SC) administered SC.
干预措施: Placebo (Drug)
BAM + ETE
Treatment 2: 175 mg BAM +350 mg ETE administered IV.
Treatment 3: 700 mg BAM +1400 mg ETE administered IV.
Treatment 4: 2800 mg BAM +2800 mg ETE administered IV.
Treatment 6: 350 mg BAM +700 mg ETE administered IV.
Unintentional Dosing: 700 mg BAM +700 mg ETE administered IV.
700 mg BAM + 1400 mg ETE 30-min (Addendum (2)) administered IV.
700 mg BAM + 1400 mg ETE 15-min (Addendum (2)) administered IV.
干预措施: Bamlanivimab (Drug)
BAM + ETE
Treatment 2: 175 mg BAM +350 mg ETE administered IV.
Treatment 3: 700 mg BAM +1400 mg ETE administered IV.
Treatment 4: 2800 mg BAM +2800 mg ETE administered IV.
Treatment 6: 350 mg BAM +700 mg ETE administered IV.
Unintentional Dosing: 700 mg BAM +700 mg ETE administered IV.
700 mg BAM + 1400 mg ETE 30-min (Addendum (2)) administered IV.
700 mg BAM + 1400 mg ETE 15-min (Addendum (2)) administered IV.
干预措施: Etesevimab (Drug)
BAM
Treatment 5: 700 mg BAM administered IV.
700 mg BAM 15-min (Addendum (2)) administered IV.
干预措施: Bamlanivimab (Drug)
BAM + VIR-7831
Treatment 7: 700 mg BAM + 500 mg VIR-7831 (Amendment (C-e)) administered IV.
干预措施: Bamlanivimab (Drug)
BAM + VIR-7831
Treatment 7: 700 mg BAM + 500 mg VIR-7831 (Amendment (C-e)) administered IV.
干预措施: VIR-7831 (Drug)
BEB
Treatment 9: 175 mg BEB (Amendment (f), Low Risk Participants) administered IV.
Treatment 12: 175 mg BEB (Amendment (f), High Risk Participants) administered IV.
70 mg BEB 140 mg/Min (Addendum 4, IV) administered IV.
175 mg BEB 140 mg/Min (Addendum 4, IV) administered IV.
175 mg BEB 350 mg/Min (Addendum 4, IV) administered IV.
1750 mg BEB 350 mg/Min (Addendum 4, IV) administered IV.
280 mg BEB (Addendum 4, SC) administered SC.
560 mg BEB (Addendum 4, SC) administered SC.
干预措施: Bebtelovimab (Drug)
BAM+ ETE + BEB
Treatment 10: 700 mg BAM +1400 mg ETE +175 mg BEB (Amendment (f), Low Risk Participants) administered IV.
Treatment 13: 700 mg BAM +1400 mg ETE +175 mg BEB (Amendment (f), High Risk Participants) administered IV.
Treatment 14: 700 mg BAM + 1400 mg ETE + 175 mg BEB(Amendment (g), High Risk, Updated Centers for Disease Control and Prevention (CDC) Criteria) administered IV.
175/700/1400 mg BAM + ETE + BEB 350 mg/Min (Addendum 4, IV) administered IV.
干预措施: Bamlanivimab (Drug)
BAM+ ETE + BEB
Treatment 10: 700 mg BAM +1400 mg ETE +175 mg BEB (Amendment (f), Low Risk Participants) administered IV.
Treatment 13: 700 mg BAM +1400 mg ETE +175 mg BEB (Amendment (f), High Risk Participants) administered IV.
Treatment 14: 700 mg BAM + 1400 mg ETE + 175 mg BEB(Amendment (g), High Risk, Updated Centers for Disease Control and Prevention (CDC) Criteria) administered IV.
175/700/1400 mg BAM + ETE + BEB 350 mg/Min (Addendum 4, IV) administered IV.
干预措施: Etesevimab (Drug)
BAM+ ETE + BEB
Treatment 10: 700 mg BAM +1400 mg ETE +175 mg BEB (Amendment (f), Low Risk Participants) administered IV.
Treatment 13: 700 mg BAM +1400 mg ETE +175 mg BEB (Amendment (f), High Risk Participants) administered IV.
Treatment 14: 700 mg BAM + 1400 mg ETE + 175 mg BEB(Amendment (g), High Risk, Updated Centers for Disease Control and Prevention (CDC) Criteria) administered IV.
175/700/1400 mg BAM + ETE + BEB 350 mg/Min (Addendum 4, IV) administered IV.
干预措施: Bebtelovimab (Drug)
结局指标
主要结局
Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load Greater Than 5.27
时间窗: Day 7
Percentage of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7. Missing data is estimated using Relevance Sequence Imputation (RSI). RSI is defined as follows: If Day 7 SARS-CoV-2 viral load is missing, then Day 7 will be imputed using data from the first available for Day 5, Day 3, Day 11, or Day 1.
Treatment 7-8, Amendments (C-e): Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27
时间窗: Day 7
Percentage of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7. Missing data is estimated using Last Observation Carried Forward (LOCF).
Treatment 9-11 Amendment (f), Low Risk Participants: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27
时间窗: Day 7
Percentage of participants with SARS-CoV-2 viral load greater than 5.27 on Day 7. Missing data is estimated using Last Observation Carried Forward (LOCF).
次要结局
- Addendum (2): Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27(Day 7)
- Treatment 14 Amendment (f) High Risk Participants, Updated CDC Criteria: Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause(Baseline through Day 29)
- Treatment 1-6 and Unintentional Dosing Arms: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load(Baseline, Day 7)
- Treatment 7-8 Amendments (C-e): Change From Baseline to Day 7 in SARS-CoV-2 Viral Load(Baseline, Day 7)
- Treatment 9-11 Amendment (f), Low Risk Participants: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load(Baseline, Day 7)
- Treatment 12 -13 Amendment (f), High Risk Participants: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load(Baseline, Day 7)
- Addendum 4, SC: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load(Baseline, Day 7)
- Treatment 9-11 Amendment (f), Low Risk Participants: Percentage of Participants Demonstrating Symptom Resolution(Day 7)
- Treatment 12 -13 Amendment (f), High Risk Participants: Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause(Baseline through Day 29)
- Treatment 14, Amendment (f) High Risk Participants Updated CDC Criteria: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load(Baseline, Day 7)
- Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants Demonstrating Symptom Resolution(Day 7)
- Treatment 12 -13, Amendment (f) High Risk Participants: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27(Day 7)
- Treatment 14, Amendment (f) High Risk Participants Updated CDC Criteria: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27(Day 7)
- Addendum (4), Arm A - Intravenous: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27(Day 7)
- Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause(Baseline through Day 29)
- Treatment 7-8, Amendment (C-E): Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause(Baseline through Day 29)
- Treatment 9-11 Amendment (f), Low Risk Participants: Percentage of Participants Who Experience COVID-19 Related Hospitalization or Death From Any Cause(Baseline through Day 29)
- Addendum 4, IV: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load(Baseline, Day 7)
- Addendum (2): Change From Baseline to Day 7 in SARS-CoV-2 Viral Load(Baseline, Day 7)
- Treatment 7-8 Amendments (C-e): Percentage of Participants Demonstrating Symptom Resolution(Day 7)
- Treatment 12 -13 Amendment (f), High Risk Participants: Percentage of Participants Demonstrating Symptom Resolution(Day 7)
- Addendum (4) Arm B - Subcutaneous: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than 5.27(Day 7)
- Treatment 14, Amendment (g) High Risk Participants Updated CDC Criteria Amendment (g): Percentage of Participants Demonstrating Symptom Resolution(Day 7)
- Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants Demonstrating Symptom Improvement(Day 7)
- Treatment 7-8 Amendments (C-E): Percentage of Participants Demonstrating Symptom Improvement(Day 7)
- Treatment 9-11 Amendment (f), Low Risk Participants: Percentage of Participants Demonstrating Symptom Improvement(Day 7)
- Treatment 12 -13 Amendment (f), High Risk Participants: Percentage of Participants Demonstrating Symptom Improvement(Day 7)
- Treatment 14 Amendment (g): Percentage of Participants Demonstrating Symptom Improvement(Day 7)
- Treatment 7-8 Amendments (C-E): Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause(Baseline through Day 29)
- Treatment 12 -13 Amendment (f), High Risk Participants: Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause(Baseline through Day 29)
- Treatment 14 Amendment (g): Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause(Baseline through Day 29)
- Treatment 1-6 and Unintentional Dosing Arms: Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause(Baseline through Day 29)
- Treatment 9-11 Amendment (f), Low Risk Participants: Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-19 Related Emergency Room Visit, or Death From Any Cause(Baseline through Day 29)
- Pharmacokinetics (PK): Mean Concentration of Bamlanivimab(Day 29)
- Pharmacokinetics (PK): Mean Concentration of Etesevimab(Day 29)
- Pharmacokinetics (PK): Mean Concentration of VIR-7831(Day 29)
- Pharmacokinetics (PK): Mean Concentration of Bebtelovimab(Day 29)