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

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ClinicalTrials.gov Identifier: NCT02622724
Recruitment Status : Terminated (Day 90 results indicate that IMP not reduced a mortality or ventilator free days)
First Posted : December 4, 2015
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
Faron Pharmaceuticals Ltd

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Respiratory Distress Syndrome, Adult Drug: Interferon beta-1a Drug: Placebo Phase 3

Detailed Description:

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 301 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 28, 2015
Actual Primary Completion Date : May 17, 2018
Actual Study Completion Date : May 17, 2018


Arm Intervention/treatment
Experimental: 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.

Drug: Interferon beta-1a
Investigational drug
Other Names:
  • FP-1201-lyo
  • Traumakine
  • ATC code L03AB07

Placebo Comparator: 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.

Drug: Placebo
Placebo for investigational drug
Other Name: FP-1201-lyo Placebo




Primary Outcome Measures :
  1. Efficacy Endpoint: Any cause death [ Time Frame: Day 28 ]
    Primary Efficacy Endpoint: Composite endpoint including any cause death at D28

  2. Efficacy Endpoint: Days free of mechanical ventilation [ Time Frame: Day 28 ]
    Primary Efficacy Endpoint: Composite endpoint including days free of mechanical ventilation (VFDsurv) within 28 days among survivors


Secondary Outcome Measures :
  1. Evaluation of Safety: Adverse events and all deaths [ Time Frame: Up to Day 28, after Day 28 and up to Day 360 ]
    Adverse events [AE] up to Day 28, AEs occurring after Day 28 if the investigator considers there is a causal relationship with the study drug and all deaths up to Day 360

  2. Efficacy Endpoint: All-cause mortality [ Time Frame: At Day 28, Day 90 and Day 180 ]
    Fatalities

  3. Efficacy Endpoint: Mortality in ICU [ Time Frame: Up to Day 28 ]
    Fatalities

  4. Efficacy Endpoint: Mortality in hospital [ Time Frame: Up to Day 28 ]
    Fatalities

  5. Other secondary efficacy endpoints: Days free of organ failure [ Time Frame: Day 28 or last day in intensive care unit [ICU] if patient has left the ICU earlier than Day 28 ]
    Sequential Organ Failure Assessment methodology

  6. Other secondary efficacy endpoints: Days free of renal support [ Time Frame: Day 28 ]
    Without renal support

  7. Other secondary efficacy endpoints: Days free of vasoactive support [ Time Frame: Day 28 ]
    Without vasoactive support

  8. Other secondary efficacy endpoints: Days free of mechanical ventilation [ Time Frame: Day 28 ]
    Without mechanical ventilation

  9. Other secondary efficacy endpoints: Number of ICU-free days [ Time Frame: Day 28 ]
    Patient not in ICU

  10. Other secondary efficacy endpoints: Number of days in hospital [ Time Frame: Day 28 ]
    Hospitalisation days

  11. Efficacy Endpoint: Presence of neutralising antibodies to IFN beta-1a [ Time Frame: Baseline and Day 28 (or last day in intensive care unit [ICU] or at withdrawal, if earlier) ]
    Immunogenicity to IFN beta-1a

  12. Efficacy Endpoint: Evaluation of pharmacodynamic [PD] using Myxovirus resistance protein A [MxA] biomarker [ Time Frame: From baseline to Day 14 ]
    Myxovirus resistance protein A

  13. Long-term efficacy endpoints relating to Quality of Life [Qol] [ Time Frame: Day 180 ]
    EuroQol 5-Dimensions 3-Levels questionnaire [EQ-5D-3L]

  14. Long-term efficacy endpoints relating to respiratory functioning [ Time Frame: Day 180 ]
    Forced expiratory volume in 1 second [FEV1]

  15. Long-term efficacy endpoints relating to neurological functioning [ Time Frame: Day 180 ]
    6-minute walk test [6MWT]

  16. Evaluation of Safety: Physical examination [ Time Frame: From baseline to Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Physical examination

  17. Evaluation of Safety: Vital signs [ Time Frame: From baseline to Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Blood pressure, heart rate, temperature

  18. Evaluation of Safety: Laboratory results [ Time Frame: From baseline to Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Biochemistry, haematology and urinalysis


Other Outcome Measures:
  1. Evaluation of Pharmacoeconomics: Days free of organ failure [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Pharmacoeconomic evaluation

  2. Evaluation of Pharmacoeconomics: Days free of renal support [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Pharmacoeconomic evaluation

  3. Evaluation of Pharmacoeconomics: Days free of vasoactive support [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Pharmacoeconomic evaluation

  4. Evaluation of Pharmacoeconomics: Days free of mechanical ventilation [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Pharmacoeconomic evaluation

  5. Evaluation of Pharmacoeconomics: Number of ICU-free days [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Pharmacoeconomic evaluation

  6. Evaluation of Pharmacoeconomics: Number of days in hospital [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Pharmacoeconomic evaluation

  7. Evaluation of Exploratory Variables relating to efficacy: Composite mortality and days free of mechanical ventilation [ Time Frame: Within 90 days ]
    Composite endpoint including mortality and days free of mechanical ventilation (VFDsurv) among survivors

  8. Evaluation of Exploratory Variables relating to efficacy: Ordered categorical endpoint defined as improvement, no change or worsening in terms of gas exchange [ Time Frame: From baseline to Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Ordered categorical endpoint defined as improvement, no change or worsening in terms of gas exchange (Partial pressure of oxygen [PaO2]/ Fraction of inspired oxygen [FiO2 ratio])

  9. Change in the treatment-specific exploratory biomarker Cluster of differentiation 73 [CD73] concentration [ Time Frame: From baseline to Day 14 ]
    Biomarker measurement

  10. Changes in levels of potential inflammatory markers [PIMs], including but not limited to, interleukin-6 and -8 [ Time Frame: From baseline to Day 14 ]
    Measurement of inflammatory markers

  11. A blood sample will be taken for pharmacogenetic analysis and correlation with other markers of the activity of FP-1201-lyo [ Time Frame: From baseline to Day 28 ]
    Any time patient is in the ICU

  12. Extended long-term follow-up: 12-month mortality rate [ Time Frame: Day 360 ]
    Fatalities

  13. Extended long-term follow-up: Quality of Life [ Time Frame: Day 360 ]
    EuroQol 5-Dimensions 3-Levels questionnaire [EQ-5D-3L]

  14. Extended long-term follow-up: Neurological functioning [ Time Frame: Day 360 ]
    6MWT

  15. Extended long-term follow-up: Respiratory functioning [ Time Frame: Day 360 ]
    FEV1



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02622724


  Show 71 Study Locations
Sponsors and Collaborators
Faron Pharmaceuticals Ltd
Investigators
Study Director: Geoffrey Bellingan, MD University College London Hospitals, NHS, London, UK
Study Director: V Marco Ranieri, Prof. MD Universita La Sapeinza Policlinico Umberto I, Rome, Italy

Responsible Party: Faron Pharmaceuticals Ltd
ClinicalTrials.gov Identifier: NCT02622724     History of Changes
Other Study ID Numbers: FPCLI002
First Posted: December 4, 2015    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Faron Pharmaceuticals Ltd:
ARDS, human
Acute Respiratory Distress Syndrome
Respiratory Insufficiency

Additional relevant MeSH terms:
Syndrome
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Interferons
Interferon-beta
Interferon beta-1a
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic