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

NCT02622724 | Terminated Phase 3 Results DMC

• 2 other identifiers: FPCLI0022014-005260-15
• Study Type: interventional
• Target: 301
• Locations: 8 countries
• Sites: 71

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.

Conditions

Respiratory Distress Syndrome, Adult

Keywords

ARDS, human; Acute Respiratory Distress Syndrome; Respiratory Insufficiency

Outcome Measures

Primary Outcomes (1)

• Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at 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).

  Day 28

Secondary Outcomes (15)

• 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 Outcomes (19)

• Evaluation of Safety: Vital Signs - Heart Rate

  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)

• Evaluation of Safety: Vital Signs - Body Temperature

  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)

• Evaluation of Safety: Vital Signs - Blood Pressure

  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)

Study Arms (2)

FP-1201-lyo 10 μg

EXPERIMENTAL

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

FP-1201-lyo Placebo

PLACEBO COMPARATOR

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

Interventions

Interferon beta-1a DRUG

Investigational drug

Also known as: FP-1201-lyo, Traumakine, ATC code L03AB07

FP-1201-lyo 10 μg

Placebo DRUG

Placebo for investigational drug

Also known as: FP-1201-lyo Placebo

FP-1201-lyo Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Faron Pharmaceuticals Ltd: lead
• Seventh Framework Programme: collaborator

Study Sites (71)

Erasmus Hospital

Brussels, B-1070, Belgium

Location

UZ Brussel

Brussels, B-1090, Belgium

Location

UZ Antwerpen

Edegem, B-2650, Belgium

Location

UZ Gent

Ghent, B-9000, Belgium

Location

CHU Charleroi Site Hôpital Civil Marie Curie

Lodelinsart, B-6042, Belgium

Location

CHU Dinant Godinne UCL Namur

Yvoir, B-5530, Belgium

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 50005, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, 10034, Czechia

Location

Hospital Usti nad Labem

Ústí nad Labem, 40011, Czechia

Location

Helsinki University Hospital

Helsinki, FI-00290, Finland

Location

Kuopio University Hospital

Kuopio, FI-70210, Finland

Location

Tampere University Hospital

Tampere, FI-33521, Finland

Location

Turku University Central Hospital

Turku, 20520, Finland

Location

Nouvel Hôpital Civil

Strasbourg, Alsace, 67091, France

Location

Centre Hospitalier Régional d'Orléans

Orléans, Loiret, 45067, France

Location

CHU D'Angers

Angers, Pays de la Loire Region, 49100, France

Location

CHU De Poitiers

Poitiers, Poitou-Charentes, 86021, France

Location

Hôpital de la Croix Rousse

Lyon, Rhône, 69004, France

Location

Hôpital Charles-Nicolle

Rouen, Seine-Maritime, 76038, France

Location

CHU Cavale Blanche

Brest, 29609, France

Location

Centre Hospitalier Universitaire de Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

Centre Hospitalier Le Mans

Le Mans, 35033, France

Location

Hôpital Nord AP-HM

Marseille, 13015, France

Location

CHRU Nancy

Nancy, 54000, France

Location

Pitié-Salpêtrière Hospital

Paris, 75013, France

Location

CHU Pontchaillou

Rennes, 35033, France

Location

CHU Bretonneau

Tours, 37044, France

Location

Hôpital Cochin, Réanimation Médicale Hospitalisation

Paris, Île-de-France Region, 75014, France

Location

Klinikum Augsburg Klinik für Anästhesiologie

Augsburg, 86156, Germany

Location

Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Universitätsklinikum Bonn Klinik und Poliklinik für Anästhesiologie

Bonn, 53127, Germany

Location

Kliniken der Stadt Köln Klinikum Merheim

Cologne, 51109, Germany

Location

Universitätsklinikum Carl Gustav Carus Klinik für Anästhesiologie und Intensivmedizin

Dresden, 01307, Germany

Location

Universitätsmedizin Göttingen Klinik für Anästhesiologie

Göttingen, 37075, Germany

Location

Universitätsklinikum Hamburg-Eppendorf Klinik für Intesivmedizin

Hamburg, 20246, Germany

Location

Universitätsklinik Leipzig Klinik und Poliklinik für Anäesthesiologie und Intensivtherapie

Leipzig, 04103, Germany

Location

Azienda Ospedaliera Universitaria Sant' Anna

Cona, 44124, Italy

Location

IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

ASST Monza

Monza, 209000, Italy

Location

Universita degli Studi di Roma "La Sapienza"

Roma, 00161, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

AOU Città della Salute e della Scienza di Torino

Torino, 10126, Italy

Location

Hospital Universitario Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital de la Santa Creu I Sant Pau

Barcelona, 08026, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitario del Henares

Coslada, 28822, Spain

Location

Hospital Universitario de Getafe

Getafe, 28905, Spain

Location

Hospital Universitario de Gran Canaria Dr Negrin

Las Palmas de Gran Canaria, 35010, Spain

Location

Hospital Universitario La Paz

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitari Son Espases

Palma de Mallorca, 07120, Spain

Location

Corporació Sanitària Parc Taulí

Sabadell, 08208, Spain

Location

Hospital Universitari Mútua de Terrassa

Terrassa, 08221, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Hospital Universitario Rio Hortega

Valladolid, 47012, Spain

Location

Bristol Royal Infirmary University Hospitals, Bristol Foundation Trust

Bristol, BS2 8HW, United Kingdom

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

University College London Hospitals, NHS Foundation Trust

London, NW1 2BU, United Kingdom

Location

Guy's and St Thomas' NHS Foundation Trust

London, SE1 7EH, United Kingdom

Location

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

St George's University Hospitals, NHS Foundation Trust

London, SW17 0QT, United Kingdom

Location

Hammersmith Hospital Imperial College Healthcre NHS Trust

London, W12 0HS, United Kingdom

Location

Charing Cross Hospital St Mary's Hospital, Imperial College Healthcare NHS Trust

London, W21NY, United Kingdom

Location

Charing Cross Hospital Imperial College Healthcare NHS Trust

London, W6 8RF, United Kingdom

Location

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, NR4 7UY, United Kingdom

Location

Nottingham University Hospitals NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

Lancashire Treaching Hospitals NHS Foundation Trust

Preston, PR2 9HT, United Kingdom

Location

Southampton General Hospital, University Hospital Southampton NHS Foundation Trust

Southampton, SO16 6YD, United Kingdom

Location

Related Publications (2)

• Jalkanen J, Khan S, Elima K, Huttunen T, Wang N, Hollmen M, Elo LL, Jalkanen S. Polymorphism in interferon alpha/beta receptor contributes to glucocorticoid response and outcome of ARDS and COVID-19. Crit Care. 2023 Mar 16;27(1):112. doi: 10.1186/s13054-023-04388-8.

  PMID: 36927455 DERIVED

• 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.

  PMID: 32065831 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; Respiratory Insufficiency

Interventions

Interferon beta-1a

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

As the study was terminated early, only a limited amount of data was available at Day 180 and Day 360.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Faron Pharmaceuticals

medical@faron.com

+3584005529411

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2015
• First Posted: December 4, 2015
• Study Start: December 23, 2015
• Primary Completion: May 17, 2018
• Study Completion: May 23, 2018
• Last Updated: March 30, 2020
• Results First Posted: March 30, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (15); GB (14); IT (6); FI (4); ES (15); CZ (3); BE (6); DE (8)