Clinical trial NCT02622724: Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Patients Having Acute Respiratory Distress Syndrome (ARDS)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Respiratory Distress Syndrome, Adult
Keywords: ARDS, human
Acute Respiratory Distress Syndrome
Respiratory Insufficiency
Lead sponsor: Faron Pharmaceuticals Ltd
Sponsor class: INDUSTRY
Collaborators: name: Seventh Framework Programme
First posted: 2015-12-04
Enrollment: 301
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28
timeFrame: Day 28
Secondary outcomes:
measure: Efficacy Endpoint: All-cause Mortality
timeFrame: At Day 28
measure: Efficacy Endpoint: Mortality in ICU
timeFrame: Up to Day 28
measure: Efficacy Endpoint: Mortality in Hospital
timeFrame: Up to Day 28
measure: Other Secondary Efficacy Endpoints: Days Free of Organ Failure
timeFrame: Day 28 or last day in intensive care unit [ICU] if patient has left the ICU earlier than Day 28
measure: Other Secondary Efficacy Endpoints: Days Free of Renal Support
timeFrame: Day 28
measure: Other Secondary Efficacy Endpoints: Days Free of Vasoactive Support
timeFrame: Day 28
measure: Other Secondary Efficacy Endpoint: Days Free of Mechanical Ventilation
timeFrame: Day 28
measure: Other Secondary Efficacy Endpoints: Number of ICU-free Days
timeFrame: Day 28
measure: Other Secondary Efficacy Endpoints: Number of Days in Hospital
timeFrame: Day 28
measure: Evaluation of Safety: Adverse Events and Deaths
timeFrame: AEs up to Day 28, only related after Day 28 and deaths up to Day 360
measure: Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a
timeFrame: Baseline and Day 28 (or last day in intensive care unit [ICU] or at withdrawal, if earlier)
measure: Efficacy Endpoint: Evaluation of Pharmacodynamic (PD) Using Myxovirus Resistance Protein A (MxA) Biomarker
timeFrame: From baseline to Day 14
measure: Long-term Efficacy Endpoint: Change in Quality of Life From Baseline to Day 180
timeFrame: Change from baseline to Day 180
measure: Long-term Efficacy Endpoints Relating to Respiratory Functioning (FEV1)
timeFrame: Day 180
measure: Long-term Efficacy Endpoints Relating to Neurological Functioning (6MWT)
timeFrame: Day 180
Other outcomes:
measure: Evaluation of Safety: Vital Signs - Heart Rate
timeFrame: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Evaluation of Safety: Vital Signs - Body Temperature
timeFrame: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Evaluation of Safety: Vital Signs - Blood Pressure
timeFrame: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Evaluation of Safety: Physical Examination
timeFrame: From baseline to Last Observation Performed (D28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Evaluation of Safety: Laboratory Results
timeFrame: From baseline to Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Evaluation of Pharmacoeconomics: Days Free of Organ Failure
timeFrame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Evaluation of Pharmacoeconomics: Days Free of Renal Support
timeFrame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Evaluation of Pharmacoeconomics: Days Free of Vasoactive Support
timeFrame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Evaluation of Pharmacoeconomics: Days Free of Mechanical Ventilation
timeFrame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Evaluation of Pharmacoeconomics: Number of ICU-free Days
timeFrame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Evaluation of Pharmacoeconomics: Number of Days in Hospital
timeFrame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal)
measure: Exploratory Variables Relating to Efficacy: Composite Endpoint (Mortality and Days Free of Mechanical Ventilation) at Day 90
timeFrame: Within 90 days
measure: Change in the Treatment-specific Exploratory Biomarker Cluster of Differentiation 73 (CD73) Concentration
timeFrame: From baseline to Day 14
measure: Changes in Levels of Potential Inflammatory Markers (PIMs)
timeFrame: From baseline to Day 14
measure: Pharmacogenetic Analysis
timeFrame: Anytime from baseline to Day 28
measure: Exploratory, Extended Long-term Follow-up: Overall Mortality at Day 360
timeFrame: Day 360 /termination of study
measure: Extended Long-term Follow-up Exploratory Endpoint: Change in Quality of Life From Baseline to Day 360
timeFrame: Change from baseline to Day 360
measure: Neurological Functioning (6MWT) at Extended Long-term Follow-up
timeFrame: Day 360
measure: Extended Long-term Follow-up Endpoint: Respiratory Functioning (FEV1) at Day 360
timeFrame: Day 360
Locations:
city: Brussels
country: Belgium
facility: Erasmus Hospital
city: Brussels
country: Belgium
facility: UZ Brussel
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: UZ Gent
city: Lodelinsart
country: Belgium
facility: CHU Charleroi Site Hôpital Civil Marie Curie
city: Yvoir
country: Belgium
facility: CHU Dinant Godinne UCL Namur
city: Hradec Králové
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Praha 10
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Usti nad Labem
country: Czechia
facility: Hospital Usti nad Labem
city: Helsinki
country: Finland
facility: Helsinki University Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Central Hospital
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil
state: Alsace
city: Orléans
country: France
facility: Centre Hospitalier Régional d'Orléans
state: Loiret
city: Angers
country: France
facility: CHU D'Angers
state: Pays-de-la-Loire
city: Poitiers
country: France
facility: CHU De Poitiers
state: Poitou-Charentes
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
state: Rhône
city: Rouen
country: France
facility: Hôpital Charles-Nicolle
state: Seine-Maritime
city: Brest
country: France
facility: CHU Cavale Blanche
city: Le Kremlin-Bicêtre
country: France
facility: Centre Hospitalier Universitaire de Bicêtre
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans
city: Marseille
country: France
facility: Hôpital Nord AP-HM
city: Nancy
country: France
facility: CHRU Nancy
city: Paris
country: France
facility: Pitié-Salpêtrière Hospital
city: Rennes
country: France
facility: CHU Pontchaillou
city: Tours
country: France
facility: CHU Bretonneau
city: Paris
country: France
facility: Hôpital Cochin, Réanimation Médicale Hospitalisation
state: Île-de-France
city: Augsburg
country: Germany
facility: Klinikum Augsburg Klinik für Anästhesiologie
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn Klinik und Poliklinik für Anästhesiologie
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus Klinik für Anästhesiologie und Intensivmedizin
city: Göttingen
country: Germany
facility: Universitätsmedizin Göttingen Klinik für Anästhesiologie
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf Klinik für Intesivmedizin
city: Köln
country: Germany
facility: Kliniken der Stadt Köln Klinikum Merheim
city: Leipzig
country: Germany
facility: Universitätsklinik Leipzig Klinik und Poliklinik für Anäesthesiologie und Intensivtherapie
city: Cona
country: Italy
facility: Azienda Ospedaliera Universitaria Sant' Anna
city: Milano
country: Italy
facility: IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: Monza
country: Italy
facility: ASST Monza
city: Roma
country: Italy
facility: Universita degli Studi di Roma "La Sapienza"
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli
city: Torino
country: Italy
facility: AOU Città della Salute e della Scienza di Torino
city: Badalona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Coslada
country: Spain
facility: Hospital Universitario del Henares
city: Getafe
country: Spain
facility: Hospital Universitario de Getafe
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Dr Negrin
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Palma De Mallorca
country: Spain
facility: Hospital Universitari Son Espases
city: Sabadell
country: Spain
facility: Corporació Sanitària Parc Taulí
city: Terrassa
country: Spain
facility: Hospital Universitari Mútua de Terrassa
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Valladolid
country: Spain
facility: Hospital Universitario Rio Hortega
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary University Hospitals, Bristol Foundation Trust
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
city: London
country: United Kingdom
facility: University College London Hospitals, NHS Foundation Trust
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: St George's University Hospitals, NHS Foundation Trust
city: London
country: United Kingdom
facility: Hammersmith Hospital Imperial College Healthcre NHS Trust
city: London
country: United Kingdom
facility: Charing Cross Hospital St Mary's Hospital, Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: Charing Cross Hospital Imperial College Healthcare NHS Trust
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospitals NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Preston
country: United Kingdom
facility: Lancashire Treaching Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital, University Hospital Southampton NHS Foundation Trust
Study officials:
affiliation: University College London Hospitals, NHS, London, UK
name: Geoffrey Bellingan, MD
role: STUDY_DIRECTOR
affiliation: Universita La Sapeinza Policlinico Umberto I, Rome, Italy
name: V Marco Ranieri, Prof. MD
role: STUDY_DIRECTOR
References:
citation: Ranieri VM, Pettila V, Karvonen MK, Jalkanen J, Nightingale P, Brealey D, Mancebo J, Ferrer R, Mercat A, Patroniti N, Quintel M, Vincent JL, Okkonen M, Meziani F, Bellani G, MacCallum N, Creteur J, Kluge S, Artigas-Raventos A, Maksimow M, Piippo I, Elima K, Jalkanen S, Jalkanen M, Bellingan G; INTEREST Study Group. Effect of Intravenous Interferon beta-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2020 Feb 25;323(8):725-733. doi: 10.1001/jama.2019.22525.