Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Patients Having Acute Respiratory Distress Syndrome (ARDS)

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

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.

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.

Inclusion Criteria:

All patients must be intubated and mechanically ventilated to diagnose ARDS and be eligible for the study

1. 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]

2. 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

3. Administration of the first dose of study drug must be planned to take place within 48 hours of moderate or severe ARDS diagnosis

4. Patient is intubated and mechanically ventilated

5. A signed informed consent form from the patient or the patient's personal legal representative or a professional legal representative must be available

6. Patient is aged ≥18 years

Exclusion Criteria:

1. Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
2. Patient is simultaneously taking part in another pharmacotherapy protocol
3. Patient is not expected to survive for 24 hours
4. 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
5. 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
6. Patient has congestive heart failure, defined as New York Heart Association class IV
7. Patient has acute left ventricular failure
8. Patient has liver failure (Child-Pugh grade C)
9. Patient has received any prior interferon
10. Patient has known hypersensitivity to natural or recombinant IFN beta or to any of the excipients
11. Patient is receiving renal dialysis therapy for chronic renal failure
12. Patient is receiving extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support
13. 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
14. Patient has burns to ≥15% of their total body surface area