A Phase 1/2/3 Adaptive Study to Evaluate the Safety, Tolerability, and Efficacy of REGN14256+Imdevimab for the Treatment of COVID-19 Patients Without Risk Factors for Progression to Severe Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 19
- 主要终点
- Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
Primary Objectives Phase 1 (Safety and Tolerability)
• Evaluate the safety and tolerability of REGN14256+imdevimab and REGN14256 monotherapy, as measured by treatment-emergent adverse events (TEAEs), injection-site reactions (ISRs), and hypersensitivity reactions
Phase 1/2 (Virologic Efficacy) • Evaluate the virologic efficacy of REGN14256+imdevimab and REGN14256 monotherapy compared to placebo, as measured by time-weighted average (TWA) change from baseline in viral load through day 7
Phase 1/2/3 (Clinical Efficacy)
• Evaluate the clinical efficacy of REGN14256+imdevimab compared to placebo, as measured by COVID-19 symptoms resolution
Secondary Objectives Phase 1 (Safety and Tolerability) • Evaluate the safety and tolerability of REGN14256+imdevimab and REGN14256 monotherapy, as measured by treatment-emergent serious adverse events (SAEs)
Phase 2 and Phase 3 (Safety and Tolerability)
• Evaluate the safety and tolerability of REGN14256+imdevimab and REGN14256 monotherapy, as measured by TEAEs, ISRs, hypersensitivity reactions, and SAEs
Phase 1, Phase 2, and Phase 3 (Virologic Efficacy, Drug Concentration, and Immunogenicity)
- Evaluate additional indicators of virologic efficacy of REGN14256+imdevimab and REGN14256 monotherapy
- Characterize the concentration-time profile of REGN14256 administered in combination with imdevimab or alone as a monotherapy
- Assess the immunogenicity of REGN14256 administered in combination with imdevimab or alone as a monotherapy
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •For the adolescent cohort in Phase 3 only: Weighs ≥40 kg at randomization
- •Has SARS-CoV-2-positive antigen or molecular diagnostic test (by validated SARSCoV-2 antigen, RT-PCR, or other molecular diagnostic assay, using an appropriate sample such as nasopharyngeal [NP], nasal, oropharyngeal [OP], or saliva) ≤72 hours prior to randomization. A historical record of a positive result is acceptable as long as the sample was collected ≤72 hours prior to randomization
- •Has symptoms consistent with COVID-19 (as determined by the investigator) with onset ≤7 days before randomization, and doesn't have a medical condition or other factors associated with high risk for progression to severe COVID-19 as outlined in the exclusion criteria
- •Maintains O2 saturation ≥93% on room air
排除标准
- •Has a medical condition or other factors associated with high risk for progression to severe COVID-19:
- •Cardiovascular disease (such as heart failure, coronary artery disease, cardiomyopathies, congenital heart disease or hypertension)
- •Chronic lung disease including chronic obstructive pulmonary disease, asthma (moderate to severe), interstitial lung disease, cystic fibrosis, and pulmonary hypertension
- •Chronic kidney disease at any stage
- •Chronic liver disease (such as alcohol-related, nonalcoholic fatty liver disease, cirrhosis)
- •Dementia or other chronic neurological condition
- •Diabetes mellitus (type 1 or type 2)
- •Immunodeficiency disease or taking immunosuppressive treatment
- •Medical-related technological dependence [for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19)]
- •Neurodevelopmental disorder (for example, cerebral palsy) or other condition that confers medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
- •Overweight (defined as BMI >25 kg/m2) or obesity (defined as BMI ≥30 kg/m2)
- •Poorly controlled HIV infection or AIDS
- •Sickle cell disease or thalassemia
- •Stroke or cerebrovascular disease
- •Prior, current (at randomization) or planned use (within time period given per CDC guidance [90 days]) of any authorized or approved vaccine for COVID-19
- •Was admitted to a hospital for COVID-19 prior to randomization, or is hospitalized (inpatient) for any reason at randomization
- •Has a known prior SARS-CoV-2 infection or positive SARS-CoV-2 serologic test
- •Has a positive SARS-CoV-2 antigen or molecular diagnostic test from a sample collected >72 hours prior to randomization
- •Has participated, or is participating, in a clinical research study evaluating COVID-19 convalescent plasma, mAbs against SARS-CoV-2, or intravenous immunoglobulin (IVIG) within 3 months or within 5 half-lives of the investigational product (whichever is longer) prior to the screening visit
- •Prior, current, or any of the following treatments: COVID-19 convalescent plasma, mAbs against SARS-CoV-2, IVIG (any indication), systemic corticosteroids (any indication), or COVID-19 treatments (authorized, approved, or investigational)
- •Has known active infection with influenza or other non-SARS-CoV-2 respiratory pathogen, confirmed by a diagnostic test
- •Has been discharged, or is planned to be discharged, to a quarantine center
- •Has participated, is participating, or plans to participate in a clinical research study evaluating any authorized, approved, or investigational vaccine for COVID-19
- •For Phase 1only: Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment and for at least 6 months after study drug administration as described in the protocol
- •Note: Other protocol-defined inclusion/ exclusion criteria apply
研究组 & 干预措施
REGN14256 + imdevimab
Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1 Phase 3: (Open label) (≥12 and <18 Years)
干预措施: REGN14256 (Drug)
REGN14256 + imdevimab
Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1 Phase 3: (Open label) (≥12 and <18 Years)
干预措施: imdevimab (Drug)
REGN14256
Phase 1, Phase 2: Randomized 1:1:1:1:1
干预措施: REGN14256 (Drug)
Imdevimab
Phase 1, Phase 2: Randomized 1:1:1:1:1
干预措施: imdevimab (Drug)
casirivimab + imdevimab
Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1
干预措施: imdevimab (Drug)
casirivimab + imdevimab
Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1
干预措施: casirivimab + imdevimab (Drug)
Placebo
Phase 1, Phase 2: Randomized 1:1:1:1:1 Phase 3: (≥18 Years): Randomized 1:1:1
干预措施: Placebo (Drug)
结局指标
主要结局
Treatment Emergent Adverse Events (TEAEs)
时间窗: Through Day 29
Phase 1
Severity of TEAEs
时间窗: Through Day 29
Severity was based on Grading. Grade 1 was less severe. Grade 5 was more severe. 1. \- Mild; Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated 2. \- Moderate; Minimal, local, or noninvasive intervention indicated; limiting age appropriate instrumental activities of daily living (ADL) 3. \- Severe; Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; ADL2 limiting self-care 4. \- Life-threatening; Life threatening consequences; urgent intervention indicated 5. \- Death; Death related to adverse events
Percentage of Participants With Injection-site Reactions (ISRs)
时间窗: Through Day 169
Phase 1 only
Severity of ISRs (Injection Site Reactions)
时间窗: Through Day 29
Severity was based on Grading. Grade 1 was less severe. Grade 5 was more severe. Grade 1 - Tenderness with or without associated symptoms (eg, warmth, erythema, itching) Grade 2 - Pain; lipodystrophy; edema; phlebitis Grade 3 - Ulceration or necrosis; severe tissue damage; operative intervention indicated Grade 4 - Life-threatening consequences; urgent intervention indicated Grade 5 - Death
Percentage of Participants With Hypersensitivity Reactions
时间窗: Through Day 169
Phase 1
Severity of Hypersensitivity Reactions Over Time
时间窗: Through Day 169
Grade 1 - Systemic intervention not indicated. Grade 2 - Oral intervention indicated Grade 3 - Bronchospasm; hospitalization indicated for clinical sequelae; intravenous intervention indicated Grade 4 - Life-threatening consequences; urgent intervention indicated Grade 5 - Death
Time-weighted Average (TWA) Daily Change From Baseline in Viral Load (log10 Copies/mL)
时间窗: Day 1 to day 7
Phase 1 Measured by SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) in nasopharyngeal (NP) swab samples
次要结局
- Severity of ISRs (Injection-Site Reactions)(Through Day 169)
- Change From Baseline in Viral Load (Phase 1)(Through Day 7)
- Change From Baseline in Viral Load(Through Day 7)
- Concentrations of REGN14256 in Serum Over Time(Through Day 169)
- Incidence and Titer of ADA to Imdevimab Over Time(Through Day 169)
- TEAEs (Treatment-Emergent Adverse Events)(Through Day 29)
- Concentrations of Imdevimab in Serum Over Time(Through Day 169)
- Incidence and Titer of Anti-drug Antibodies (ADA) to REGN14256 Over Time(Through Day 169)
- Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs)(Through Day 169)
- Severity of TEAEs (Treatment-Emergent Adverse Event)(Through Day 29)
- Percentage of Participants With ISRs (Injection-Site Reactions)(Through Day 169)
- Percentage of Participants With Hypersensitivity Reactions(Through Day 169)
- Severity of Hypersensitivity Reactions Over Time(Through Day 169)
- Percentage of Participants With Treatment-emergent SAEs (Serious Adverse Events)(Through Day 169)
- Time-weighted Average Change From Baseline in Viral Load(Through Day 169)
- Percentage of Participants With Viral Loads Below the Limit of Detection(Through Day 169)
- Concentrations of REGN14256 in Serum Over Time (Phase 1)(Through Day 169)
- Concentrations of Imdevimab in Serum Over Time (Phase 1)(Through Day 169)