A Phase 2, Randomized, Placebo-controlled, Participant and Investigator Blinded, Multi-center Study to Assess Efficacy and Safety of MAS825 for the Treatment of SARS-CoV-2 Infected Patients With COVID-19 Pneumonia and Impaired Respiratory Function
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier)
研究概览
简要总结
This clinical study was designed to assess the efficacy and safety of MAS825 for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infected patients with coronavirus disease 2019 (COVID-19) pneumonia and impaired respiratory function.
详细描述
This was a Phase 2, randomized, placebo -controlled, participant and investigator blinded, multi-center study to assess efficacy and safety of MAS825 for the treatment of SARS-CoV-2 infected patients with COVID-19 pneumonia and impaired respiratory function.
The study consisted of five study periods:
Screening / Baseline / Treatment visit (Day -1 to 1): Lasted up to a maximum of 24 hours and comprised a screening / baseline assessment. This visit was used to confirm that the study inclusion and exclusion criteria were met and served as baseline assessment prior to randomization. Participants were randomized as soon as possible, but within a maximum of 24 hours after screening in a 1:1 ratio receiving a single intravenous infusion of MAS825 or placebo in addition to standard of care (SoC) on Day -1 to 1.
Treatment period (Day 2-15): Study assessments were conducted every 2 days for hospitalized participants. If participants were discharged from the hospital prior to Day 15, assessments on the day of discharge were performed according to the schedule listed under Day 15 and those participants returned to the site for the Day 15 assessment (all other visits between discharge and Day 15 were omitted).
Follow-up (Day 16-29): After completion of the treatment period, participants were observed until Day 29 or discharged from hospital, whichever was sooner. Study assessments were conducted every 2 days for domiciled participants. If participants were discharged from hospital prior to Day 29, a study visit conducted by telephone was performed on Day 29 (all other visits between discharge and Day 29 were omitted).
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients aged ≥18 years at screening
- •Signed Informed Consent Form (ICF) by patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representative (if allowed according to local requirements)
- •Clinically diagnosed with the SARS-CoV-2 virus by polymerase chain reaction (PCR) or by other approved diagnostic methodology within 7 days prior to randomization
- •Hospitalized with COVID-19-induced pneumonia evidenced by chest x-ray, computed tomography scan (CT scan) or magnetic resonance scan (MR scan) (taken within 5 days prior to randomization)
- •Impaired respiratory function, defined as peripheral oxygen saturation (SpO2) ≤93% on room air or partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) <300 millimeter of mercury (mmHg) at time of screening For cities located at altitudes greater than 2500 m above sea level, these will be substituted with SpO2 <90% and PaO2/FiO2 <250 mmHg
- •Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score of ≥10 at time of screening
- •CRP ≥20 mg/L or ferritin level ≥600 μg/L at screening
- •Body weight between 45 kg and 145 kg, inclusive, at screening
- •Ability to comply with the study protocol, in the investigator's judgment
排除标准
- •History of hypersensitivity to the investigational treatment or their excipients or to drugs of similar chemical classes
- •Suspected active or chronic bacterial (including Mycobacterium tuberculosis), fungal, viral, or other infection with the exception of SARS-CoV-2
- •In the opinion of the investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatment
- •Intubated prior to randomization
- •Patients who have explicitly expressed the wish not to receive intensive care support when this would be indicated based on their condition
- •Previous treatment with anti-rejection and immunomodulatory drugs within the past 2 weeks, or within the past 30 days or 5 half-lives (whichever is the longer) for immunomodulatory therapeutic antibodies or prohibited drugs, with the exception of anti-viral therapies or corticosteroids
- •For COVID-19 infection, ongoing corticosteroid treatment is permitted at doses as per local SoC
- •For non-COVID-19 disorders, ongoing corticosteroid treatment is permitted at doses up to and including prednisolone 10 mg daily or equivalent.
- •Serum alanine transaminase (ALT) or aspartate transaminase (AST) >5 times upper limit of normal detected within 24 hours at screening/baseline (according to local laboratory reference ranges) or other evidence of severe hepatic impairment.
- •Absolute peripheral blood neutrophil count of ≤1000/mm^3
- •Estimated GFR (eGFR) ≤30 mL/min/1.73m^2 (based on CKD-EPI formula)
- •Pregnant or breastfeeding, or positive urine or serum pregnancy test in a pre-dose examination
- •Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they agree to abstain from any sexual intercourse for a total of 29 days after randomization (the 14-day treatment period plus a 14-day follow-up period).
- •Current participation in any other investigational trials, with the exception of (not yet) approved COVID-19 therapies that are considered (local) standard of care.
研究组 & 干预措施
MAS825 + SoC
Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC
干预措施: MAS825 (Drug)
MAS825 + SoC
Single dose of MAS825 10 mg/kg by intravenous infusion in addition to SoC
干预措施: Standard of Care (SoC) (Drug)
Placebo + SoC
Single dose of matching Placebo by intravenous infusion in addition to SoC
干预措施: Placebo (Other)
Placebo + SoC
Single dose of matching Placebo by intravenous infusion in addition to SoC
干预措施: Standard of Care (SoC) (Drug)
结局指标
主要结局
APACHE II Severity of Disease Score on Day 15 or on the Day of Discharge (Whichever is Earlier)
时间窗: up to Day 15
The APACHE II ("Acute Physiology And Chronic Health Evaluation II") is a severity-of-disease classification system. An integer score from 0 to 71 is computed based on several measurements; higher scores correspond to more severe disease and a higher risk of death. In practice, it is rare for any participant to accumulate more than 55 points. APACHE II score was measured on Day 15 or on the day of discharge (whichever was earlier). Participants who died on Day 15 or earlier were assigned the highest observed APACHE II score of any of the participants at any time during the trial (worst case imputation for deaths). Missing data values of the parameters required for the derivation of the APACHE II score were replaced by the last available assessment.
次要结局
- Serum C-reactive Protein (CRP) Levels(Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15)
- Ferritin Levels(Baseline, days 2, 4, 6, 8, 10, 12, 14 and 15)
- Number of Participants Not Requiring Mechanical Ventilation for Survival(Until Day 15 (Assessments on Days 2, 4, 6, 8, 10, 12, 14 and 15) and until Day 29 (Additional assessments on Days 17, 19, 21, 23, 25, 27 and 29))
- Number of Participants With at Least One-point Improvement From Baseline in Clinical Status(Baseline, Day 15 and Day 29)
- Clinical Status Over Time(Baseline, days 2, 4, 6, 8, 10, 12, 14, 15, 17, 19, 21, 23, 25, 27, 29, 45 and 127)