A Phase III Double-blind, Randomised, Parallel-Group Comparison of the Efficacy and Safety of FP-1201-lyo (Recombinant Human IFN Beta-1a) and Placebo in the Treatment of Patients With Moderate or Severe Acute Respiratory Distress Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 301
- 试验地点
- 71
- 主要终点
- Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28
研究概览
简要总结
In this study effectiveness and safety of a new drug FP-1201-lyo (recombinant human interferon beta-1a) is compared to placebo. Investigation is conducted with patients who have acute respiratory distress syndrome (ARDS). The new drug is expected to reduce the time which a patient need to be on the ventilator and improve patient's chances of survival. Currently there are no approved drugs for treating moderate or severe ARDS patients.
详细描述
This is a Phase III clinical study to investigate the efficacy and safety of FP-1201-lyo (recombinant human interferon [IFN] beta-1a) compared to placebo in patients diagnosed with moderate or severe acute respiratory distress syndrome (ARDS). Primary objective is to demonstrate the efficacy of FP-1201-lyo in improving the clinical course and outcome based on survival and need for mechanical ventilation. Currently there are no approved drugs for treating moderate or severe ARDS patients.
FP-1201-lyo is a lyophilised powder form of recombinant human IFN beta-1a reconstituted in water for injection and is administered intravenously.
Recombinant human IFN beta-1a is an approved treatment for patients for other indication and its safety profile in such patients is well characterised.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must be intubated and mechanically ventilated to diagnose ARDS and be eligible for the study
- •Patient has a diagnosis of moderate or severe ARDS according to the Berlin definition of ARDS:
- •Acute onset of respiratory failure within 1 week of a known clinical insult or new or worsening respiratory symptoms
- •Respiratory failure associated with known ARDS risk factors and not fully explained by either cardiac failure or fluid overload (an objective assessment of cardiac failure or fluid overload is needed if no risk factors for ARDS [moderate or severe ARDS] are present)
- •Radiological abnormalities on chest X-ray or on computerised tomography scan, i.e., bilateral opacities that are not fully explained by effusions, nodules, masses or lobar/lung collapse
- •Hypoxaemia:
- •Moderate ARDS: PaO2/FiO2 >100 mmHg (>13.3 kPa) to ≤200 mmHg (≤26.6 kPa) with positive end expiratory pressure (PEEP) ≥5 cmH2O
- •Severe ARDS: PaO2/FiO2 ≤100 mmHg (≤13.3 kPa) with positive end expiratory pressure [PEEP] ≥5 centimeter of water [cmH2O]
- •The radiological and hypoxaemia criteria (1.3 and 1.4) must be met within the same 24-hour period. The time of onset of ARDS is when the last of the two specified ARDS criteria is met
- •Administration of the first dose of study drug must be planned to take place within 48 hours of moderate or severe ARDS diagnosis
- •Patient is intubated and mechanically ventilated
- •A signed informed consent form from the patient or the patient's personal legal representative or a professional legal representative must be available
- •Patient is aged ≥18 years
排除标准
- •Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
- •Patient is simultaneously taking part in another pharmacotherapy protocol
- •Patient is not expected to survive for 24 hours
- •Patient has an underlying clinical condition where, in the opinion of the Investigator, it would be extremely unlikely that the patient would come off ventilation, e.g., motor neurone disease, Duchenne muscular dystrophy or rapidly progressive interstitial pulmonary fibrosis
- •Patient has severe chronic obstructive pulmonary disease requiring long-term home oxygen therapy or mechanical ventilation (non-invasive ventilation or via tracheotomy) except for continuous positive airway pressure (CPAP) or bi-level positive airway pressure used solely for sleep-disordered breathing
- •Patient has congestive heart failure, defined as New York Heart Association class IV
- •Patient has acute left ventricular failure
- •Patient has liver failure (Child-Pugh grade C)
- •Patient has received any prior interferon
- •Patient has known hypersensitivity to natural or recombinant IFN beta or to any of the excipients
- •Patient is receiving renal dialysis therapy for chronic renal failure
- •Patient is receiving extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support
- •Patient has had any form of mechanical ventilation (invasive or non-invasive, excluding CPAP alone) for longer than 48 hours prior to the diagnosis of ARDS. Non-invasive ventilation has to be continuously applied for at least 12 hours per day in these 48 hours
- •Patient has burns to ≥15% of their total body surface area
研究组 & 干预措施
FP-1201-lyo 10 μg
FP-1201-lyo 10 μg (Interferon beta-1a) will be administered once daily as an intravenous bolus injection for 6 days.
Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection.
干预措施: Interferon beta-1a (Drug)
FP-1201-lyo Placebo
FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days.
Investigational placebo product is lyophilisate for solution for injection which will be reconstituted in water for injection.
干预措施: Placebo (Drug)
结局指标
主要结局
Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28
时间窗: Day 28
VFDsurv is a composite measure of all-cause mortality and the number of days free of mechanical ventilation (VFDsurv) within 28 days among survivors. Ventilator-free days (VFDs) correspond to those days when unassisted breathing (UAB) was possible for a complete calendar day. UAB was defined as: spontaneously breathing with face mask, nasal prong oxygen or room air, T-piece breathing, tracheostomy mask breathing, CPAP less than or equal to 5 cmH2O without pressure support or intermittent mandatory ventilation assistance, use of CPAP or BIPAP solely for sleep apnoea management. A patient was reported as ventilator-free after 2 consecutive calendar days of unassisted breathing (a VFD value of 0 is assigned to patients who die without initiating UAB or who require more than 28 days of mechanical ventilation. All patients who die before Day28 are assigned a VFDsurv value of -1).
次要结局
- Efficacy Endpoint: All-cause Mortality(At Day 28)
- Efficacy Endpoint: Mortality in ICU(Up to Day 28)
- Efficacy Endpoint: Mortality in Hospital(Up to Day 28)
- Other Secondary Efficacy Endpoints: Days Free of Organ Failure(Day 28 or last day in intensive care unit [ICU] if patient has left the ICU earlier than Day 28)
- Other Secondary Efficacy Endpoints: Days Free of Renal Support(Day 28)
- Other Secondary Efficacy Endpoints: Days Free of Vasoactive Support(Day 28)
- Other Secondary Efficacy Endpoint: Days Free of Mechanical Ventilation(Day 28)
- Other Secondary Efficacy Endpoints: Number of ICU-free Days(Day 28)
- Other Secondary Efficacy Endpoints: Number of Days in Hospital(Day 28)
- Evaluation of Safety: Adverse Events and Deaths(AEs up to Day 28, only related after Day 28 and deaths up to Day 360)
- Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a(Baseline and Day 28 (or last day in intensive care unit [ICU] or at withdrawal, if earlier))
- Efficacy Endpoint: Evaluation of Pharmacodynamic (PD) Using Myxovirus Resistance Protein A (MxA) Biomarker(From baseline to Day 14)
- Long-term Efficacy Endpoint: Change in Quality of Life From Baseline to Day 180(Change from baseline to Day 180)
- Long-term Efficacy Endpoints Relating to Respiratory Functioning (FEV1)(Day 180)
- Long-term Efficacy Endpoints Relating to Neurological Functioning (6MWT)(Day 180)