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

NCT ID: NCT02622724

Last Updated: 2020-03-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 301 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-23
• Study Completion Date: 2018-05-23

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.

Conditions

Respiratory Distress Syndrome, Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Interferon beta-1a

Intervention Type: DRUG

Investigational 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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo for investigational drug

Interventions

Interferon beta-1a

Investigational drug

Intervention Type: DRUG

Placebo

Placebo for investigational drug

Intervention Type: DRUG

Other Intervention Names

FP-1201-lyo; Traumakine; ATC code L03AB07; FP-1201-lyo Placebo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Seventh Framework Programme

OTHER

Sponsor Role: collaborator

Faron Pharmaceuticals Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Geoffrey Bellingan, MD

Role: STUDY_DIRECTOR

University College London Hospitals, NHS, London, UK

V Marco Ranieri, Prof. MD

Role: STUDY_DIRECTOR

Universita La Sapeinza Policlinico Umberto I, Rome, Italy

Locations

Erasmus Hospital

Brussels, , Belgium

UZ Brussel

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

UZ Gent

Ghent, , Belgium

CHU Charleroi Site Hôpital Civil Marie Curie

Lodelinsart, , Belgium

CHU Dinant Godinne UCL Namur

Yvoir, , Belgium

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Fakultni nemocnice Kralovske Vinohrady

Prague, , Czechia

Hospital Usti nad Labem

Ústí nad Labem, , Czechia

Helsinki University Hospital

Helsinki, , Finland

Kuopio University Hospital

Kuopio, , Finland

Tampere University Hospital

Tampere, , Finland

Turku University Central Hospital

Turku, , Finland

Nouvel Hôpital Civil

Strasbourg, Alsace, France

Centre Hospitalier Régional d'Orléans

Orléans, Loiret, France

CHU D'Angers

Angers, Pays de la Loire Region, France

CHU De Poitiers

Poitiers, Poitou-Charentes, France

Hôpital de la Croix Rousse

Lyon, Rhône, France

Hôpital Charles-Nicolle

Rouen, Seine-Maritime, France

CHU Cavale Blanche

Brest, , France

Centre Hospitalier Universitaire de Bicêtre

Le Kremlin-Bicêtre, , France

Centre Hospitalier Le Mans

Le Mans, , France

Hôpital Nord AP-HM

Marseille, , France

CHRU Nancy

Nancy, , France

Pitié-Salpêtrière Hospital

Paris, , France

CHU Pontchaillou

Rennes, , France

CHU Bretonneau

Tours, , France

Hôpital Cochin, Réanimation Médicale Hospitalisation

Paris, Île-de-France Region, France

Klinikum Augsburg Klinik für Anästhesiologie

Augsburg, , Germany

Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum

Berlin, , Germany

Universitätsklinikum Bonn Klinik und Poliklinik für Anästhesiologie

Bonn, , Germany

Kliniken der Stadt Köln Klinikum Merheim

Cologne, , Germany

Universitätsklinikum Carl Gustav Carus Klinik für Anästhesiologie und Intensivmedizin

Dresden, , Germany

Universitätsmedizin Göttingen Klinik für Anästhesiologie

Göttingen, , Germany

Universitätsklinikum Hamburg-Eppendorf Klinik für Intesivmedizin

Hamburg, , Germany

Universitätsklinik Leipzig Klinik und Poliklinik für Anäesthesiologie und Intensivtherapie

Leipzig, , Germany

Azienda Ospedaliera Universitaria Sant' Anna

Cona, , Italy

IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, , Italy

ASST Monza

Monza, , Italy

Universita degli Studi di Roma "La Sapienza"

Roma, , Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, , Italy

AOU Città della Salute e della Scienza di Torino

Torino, , Italy

Hospital Universitario Germans Trias i Pujol

Badalona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital de la Santa Creu I Sant Pau

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clínic i Provincial de Barcelona

Barcelona, , Spain

Hospital Universitario del Henares

Coslada, , Spain

Hospital Universitario de Getafe

Getafe, , Spain

Hospital Universitario de Gran Canaria Dr Negrin

Las Palmas de Gran Canaria, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitari Son Espases

Palma de Mallorca, , Spain

Corporació Sanitària Parc Taulí

Sabadell, , Spain

Hospital Universitari Mútua de Terrassa

Terrassa, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Hospital Universitario Rio Hortega

Valladolid, , Spain

Bristol Royal Infirmary University Hospitals, Bristol Foundation Trust

Bristol, , United Kingdom

University Hospital of Wales

Cardiff, , United Kingdom

Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

University College London Hospitals, NHS Foundation Trust

London, , United Kingdom

Guy's and St Thomas' NHS Foundation Trust

London, , United Kingdom

King's College Hospital NHS Foundation Trust

London, , United Kingdom

St George's University Hospitals, NHS Foundation Trust

London, , United Kingdom

Hammersmith Hospital Imperial College Healthcre NHS Trust

London, , United Kingdom

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

London, , United Kingdom

Charing Cross Hospital Imperial College Healthcare NHS Trust

London, , United Kingdom

Norfolk and Norwich University Hospitals NHS Foundation Trust

Norwich, , United Kingdom

Nottingham University Hospitals NHS Trust

Nottingham, , United Kingdom

Lancashire Treaching Hospitals NHS Foundation Trust

Preston, , United Kingdom

Southampton General Hospital, University Hospital Southampton NHS Foundation Trust

Southampton, , United Kingdom

Countries

Belgium; Czechia; Finland; France; Germany; Italy; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36927455 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32065831 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-005260-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FPCLI002

Identifier Type: -

Identifier Source: org_study_id