A Randomized, Double-blind, Placebo-Controlled, Phase 2/3 Study to Evaluate the Efficacy and Safety of LY3819253 and LY3832479 in Participants With Mild to Moderate COVID-19 Illness
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 3,307
- 试验地点
- 12
- 主要终点
- Phase 3: Percentage of Participants Who Experience COVID-Related Hospitalization or Death From Any Cause in 2800 mg Bamlanivumab/2800 mg Etesevimab, 700 mg Bamlanivimab/1400mg Etesevimab and Their Placebo Groups
研究概览
简要总结
The purpose of this study is to measure how well LY3819253 and LY3832479 work against the virus that causes COVID-19. LY3819253 and LY3832479 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 weeks and includes one required visit to the study site, with the remainder of assessments performed in the home or by phone.
Pediatric participants, with mild to moderate COVID-19 illness, will enroll in a single-arm (Arm 22), open-label addendum to evaluate the pharmacokinetics and safety of LY3819253 and LY3832479. Enrollment began on March 31, 2021, and completed on September 24, 2021.
Pediatric participants, with mild to moderate COVID-19 illness, will enroll in a single-arm (Arm 23), open-label addendum to evaluate the pharmacokinetics and safety of LY3853113. Enrollment began on August 19, 2022, and completed on February 21, 2023.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Some treatment arms are open label.
入排标准
- 年龄范围
- 0 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Are currently not hospitalized. (Not applicable to participants in treatment arm 22.)
- •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. (Not applicable to participants in treatment arm 22.)
- •Must have sample taken for test confirming viral infection no more than 3 days prior to starting the drug infusion
- •Are males or females, including pregnant females who agree to contraceptive requirements
- •Understand and agree to comply with planned study procedures
- •Agree to the collection of nasopharyngeal swabs and venous blood. (Not applicable to participants in treatment arms 20-21.)
- •The participant or legally authorized representative give signed informed consent and/or assent
- •Participants in treatment arms 7-9, 13-14, and 18-21 ONLY
- •Are greater than or equal to (≥)18 years of age and must satisfy at least one of the following at the time of screening
- •Are pregnant
- •Are ≥65 years of age
- •Have a body mass index (BMI) ≥35
- •Have chronic kidney disease (CKD)
- •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 (CVD), OR
- •hypertension, OR
- •chronic obstructive pulmonary disease (COPD) or other chronic respiratory disease
- •Are 12-17 years of age (inclusive) AND satisfy at least one of the following at the time of screening
- •Are pregnant
- •Have a body mass index (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
- •Participants in treatment arm 22 ONLY
- •Are 0 (≥ 32 weeks gestational age AND ≥ 1.5 kilograms [kg]) to 17 years of age (inclusive) AND satisfy at least one of the following risk factors at the time of screening
- •Are pregnant
- •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, autism, or Down syndrome (FAIR Health 2020; Spreat et al. 2020)
- •Have a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)
- •Have asthma, cystic fibrosis, reactive airways disease 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, or
- •Are less than (<) one year of age.
- •Have one or more COVID-19 symptoms
- •Shortness of breath/difficulty breathing
- •Sore throat
- •Tiredness
- 另有 19 项未显示
排除标准
- •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) less than (<)300, respiratory rate greater than or equal to (≥)30 per minute, heart rate ≥125 per minute due to COVID-19
- •Require mechanical ventilation or anticipated impending need for mechanical ventilation due to COVID-19
- •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 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 received convalescent COVID-19 plasma treatment
- •Have participated in a previous SARS-CoV-2 vaccine study or have received a SARS-CoV-2 vaccine
- •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
- •Mothers who are breast feeding
- •Participants in Treatment Arm 22 ONLY
- •Have a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) in the opinion of the investigator
- •Are currently hospitalized for treatment of COVID-
- •Other reasons for hospitalization are acceptable.
- •Participants in treatment arm 23 ONLY
- •SpO2 ≤ 93% on room air at sea level, or while on chronic oxygen therapy and/or respiratory support due to underlying non-COVID-19 related comorbidity, respiratory rate ≥30 per minute, and heart rate ≥125 per minute due to COVID-19 (FDA February 2021)
- •Require mechanical ventilation or anticipated impending need for mechanical ventilation due to COVID-19
- •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 received treatment with a SARS-CoV-2 specific monoclonal antibody or remdesivir within 90 days before dosing.
- •Have received convalescent COVID-19 plasma treatment within 90 days before dosing
- •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 currently pregnant or breast feeding
研究组 & 干预措施
Placebo
Placebo administered IV
干预措施: Placebo (Drug)
LY3819253
700 mg, 2800 mg, 7000 mg, LY3819253 administered intravenously (IV)
干预措施: LY3819253 (Drug)
LY3819253 + LY3832479
350 mg, 700 mg, 2800 mg LY3819253 + 700 mg, 1400 mg, 2800 mg LY3832479 administered IV or subcutaneously (SQ)
干预措施: LY3819253 (Drug)
LY3819253 + LY3832479
350 mg, 700 mg, 2800 mg LY3819253 + 700 mg, 1400 mg, 2800 mg LY3832479 administered IV or subcutaneously (SQ)
干预措施: LY3832479 (Drug)
LY3819253 + LY3832479 (Pediatric Addendum, Arm 22)
LY3819253 dose based upon weight (weight Group: ≥40 kilogram (kg) = 700 mg dose, >20 kg to <40 kg = 350 mg dose, >12 kg to 20 kg = 175 mg dose and 1.5 kg to 12 kg = 15 mg/kg dose) and LY3832479 dose based upon weight (weight Group: ≥40 kg = 1400 mg dose, >20 kg to <40 kg = 700 mg dose, >12 kg to 20 kg = 350 mg dose and 1.5 kg to 12 kg = 30 mg/kg dose) administered IV.
干预措施: LY3819253 (Drug)
LY3819253 + LY3832479 (Pediatric Addendum, Arm 22)
LY3819253 dose based upon weight (weight Group: ≥40 kilogram (kg) = 700 mg dose, >20 kg to <40 kg = 350 mg dose, >12 kg to 20 kg = 175 mg dose and 1.5 kg to 12 kg = 15 mg/kg dose) and LY3832479 dose based upon weight (weight Group: ≥40 kg = 1400 mg dose, >20 kg to <40 kg = 700 mg dose, >12 kg to 20 kg = 350 mg dose and 1.5 kg to 12 kg = 30 mg/kg dose) administered IV.
干预措施: LY3832479 (Drug)
LY3853113 (Pediatric Addendum, Arm 23)
LY3853113 dose based upon weight (Weight Group: ≥3.3 to ≤12 kg = 3 mg/kg dose, >12 to ≤20 kg = 43.75 mg dose, >20 to <40 kg = 87.5 mg dose, ≥40 kg = 175 mg dose) administered IV.
干预措施: LY3853113 (Drug)
结局指标
主要结局
Phase 3: Percentage of Participants Who Experience COVID-Related Hospitalization or Death From Any Cause in 2800 mg Bamlanivumab/2800 mg Etesevimab, 700 mg Bamlanivimab/1400mg Etesevimab and Their Placebo Groups
时间窗: Baseline through Day 29
COVID-19 Related Deterioration (yes/no) was defined as a participant experiencing COVID-19-related hospitalization (defined as 24 hours of acute care) or death from any cause by Day 29.
Phase 3: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than a Prespecified Threshold in Arms 350 mg Bamlanivimab/700 mg Etesevimab and Placebo
时间窗: Day 7
SARS-CoV-2 persistent high viral load (yes/no) was defined as ribonuclease P(RP) normalized viral load \>=5.27 vs otherwise.
Phase 2: Change From Baseline to Day 11 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load
时间窗: Baseline, Day 11
SARS-CoV-2 viral load was based on nasopharyngeal swab sampling for reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2. Least squares (LS) mean values were determined using a mixed-effects model repeated-measures (MMRM) that included log base 10 transformed baseline as a covariate, treatment, day, treatment-by-day interaction as fixed effects. If Day 11 SARS-CoV-2 viral load was missing, the earliest measurement closest to the Day 11 visit, but within 4 days (Day 7-Day 15), was used for the Day 11 value. If no measurements were available, the Day 11 viral load was treated as missing at random (MAR) in the analysis. Viral load is reported as normalized viral load and is unitless.
Phase 2: Percentage of Participants Who Experience a Serious Adverse Event(s) SAE(s)
时间窗: Baseline through Day 85
An SAE was defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other different situations will have medical or scientific judgment to determine if they are SAE. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality are reported in the Adverse Events section.
Phase 3 and Phase 2/3 [Arm 22], Pharmacokinetics (PK): Mean Concentrations of LY3819253 (Bamlanivimab)
时间窗: Day 29 Post-dose
Mean Concentration of Bamlanivimab in the presence of Etesevimab is reported. Due to the limited number of pediatric participants across all study arms in phase 3, PK concentration summary data was combined including phase 3 and phase 2/3 (Pediatric addendum, Arm 22) reporting arms. All pediatric participants from Phase 3 trial arms including Arm 22 who contributed data to the required outcome (PK concentration at Day 29) were included in the PK summary.
Phase 3 and Phase 2/3 [Arm 22], Pharmacokinetics (PK): Mean Concentrations of LY3832479 (Etesevimab)
时间窗: Day 29 Post-dose
Mean Concentration of Etesevimab in the presence of Bamlanivimab is reported. Due to the limited number of pediatric participants across all study arms in phase 3, PK concentration summary data was combined including phase 3 and phase 2/3 (Pediatric addendum, Arm 22) reporting arms. All pediatric participants from Phase 3 trial arms including Arm 22 who contributed data to the required outcome (PK concentration at Day 29) were included in the PK summary.
Phase 2/3, PK: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-∞) for Bebtelovimab [Arm 23]
时间窗: Day 60 Post-dose
AUC0-∞ for Bebtelovimab was reported.
次要结局
- Phase 3: Percentage of Participants Demonstrating Symptom Improvement(Day 11)
- Phase 3: Time to SARS-CoV-2 Viral Clearance(Baseline through Day 29)
- Phase 2, PK: Mean Concentration of Etesevimab in the Presence of Bamlanivimab(Day 29 Post-dose)
- Phase 2/3: Percentage of Participants With SARS-CoV-2 Viral Load Greater Than a Prespecified Threshold [Arm 22](Day 7)
- Phase 2/3: Time to Complete Symptom Resolution [Arm 22](Baseline through Day 29)
- Phase 3: Percentage of Participants Demonstrating Symptom Resolution(Day 11)
- Phase 3: Change From Baseline to Day 7 in SARS-CoV-2 Viral Load(Baseline, Day 7)
- Phase 3: Time to Sustained Symptom Resolution(Baseline through Day 29)
- Phase 2, Pharmacokinetics (PK): Mean Concentration of Bamlanivimab Alone and in the Presence of Etesevimab(Day 29 Post-dose)
- Phase 2: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death From Any Cause(Baseline through Day 85)
- Phase 2: Time to SARS-CoV-2 Viral Clearance(Baseline through Day 29)
- Phase 2/3: Percentage of Participants Who Experience COVID-19 Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death From Any Cause [Arm 22](Baseline through Day 29)
- Phase 2/3: Change From Baseline to Day 7 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Load [Arm 22](Baseline, Day 7)
- Phase 2/3: Time to Sustained Complete Symptom Resolution [Arm 22](Baseline through Day 29)
- Phase 3: Percentage of Participants Who Experience COVID-Related Hospitalization, COVID-Related Emergency Room (ER) Visit, or Death From Any Cause(Baseline through Day 85)
- Phase 2: Percentage of Participants Demonstrating Symptom Resolution(Day 11)
- Phase 2: Percentage of Participants Demonstrating Symptom Improvement(Day 11)
- Phase 2: Change From Baseline to Day 11 in SARS-CoV-2 Viral Load Among Participants Enrolled With Recent Symptoms Prior to Randomization(Baseline, Day 11)
- Phase 2/3: Time to SARS-CoV-2 Viral Clearance [Arm 22](Baseline through Day 29)