Clinical trial NCT00789685: Safety, Tolerability and Preliminary Efficacy of FP-1201 in ALI and ARDS. Phase I/II
Official title: A Phase I/II Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of FP-1201 (Recombinant Human Interferon Beta) in the Treatment of Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Acute Lung Injury
Acute Respiratory Distress Syndrome
Keywords: Open label
Lead sponsor: Faron Pharmaceuticals Ltd
Sponsor class: INDUSTRY
First posted: 2008-11-13
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to assess the safety, tolerability and preliminary efficacy of FP-1201 (Interferon Beta) in patients with Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).

Detailed description: This was a phase I/II open-label study to assess the safety, tolerability and preliminary efficacy of FP-1201 (IFN β-1a) in the treatment of patients with ALI and ARDS.

The primary objective in the study was to evaluate the safety and tolerability of FP-1201 in patients with ALI/ARDS and to assess the safety, tolerability and preliminary efficacy of the optimum tolerated dose (OTD) in patients likely to derive clinical benefit.

The study consisted of a dose escalation phase to determine the maximum tolerated dose (MTD) and OTD followed by a separate cohort expansion phase in which the OTD was administered.

Eligibility criteria: Inclusion Criteria:

* Adult male or female patients with ALI/ARDS confirmed by the combination of the following diagnostic criteria:

  * An initiating clinical condition (e.g. sepsis, pneumonia, aspiration pneumonia, pancreatitis etc.)
  * Acute onset
  * Bilateral infiltrates documented by chest radiograph at end-aspiratory position
  * The absence of clinical evidence of left atrial hypertension
  * ALI: partial pressure of oxygen (PaO2) / fraction of inspired oxygen (FiO2) ratio ≤300 mmHg in a stable state after the patient has adapted to standardised ventilation. (Within the UK this equates to \<40kPa)
  * ARDS: PaO2 /FiO2 ≤200 mmHg in a stable state after the patient has adapted to standardised ventilation. (Within the UK this equates to \<26.7kPa)
* Provision of signed written informed consent from the patient or patients legally authorized representative.
* Age greater than or equal to 18.
* Initiation of study drug within 48 hours of the diagnosis of ALI/ARDS.
* All patients at entry are required to be receiving mechanical ventilatory support.
* Only patients who are considered suitable for active life support should be enrolled in the study.
* No clinical evidence of left atrial hypertension that would explain the pulmonary infiltrates; if measured the pulmonary arterial wedge pressure should be less than or equal to 18mmHg

Exclusion Criteria:

* Patients with burns.
* Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.
* Patients with significant Chronic Obstructive Pulmonary Disease requiring ongoing treatment e.g. chronic use of oxygen or ventilatory support at home prior to admission.
* Patients with primary lung cancer or the presence of secondary metastases in the lungs.
* Patients requiring treatment for congestive heart failure.
* Patients receiving renal dialysis therapy for chronic renal failure.
* Patients taking immunomodulatory therapy or oral steroids on admission.
* Prior use of interferon.
* Inability to maintain blood pressure to ensure adequate end organ perfusion. It should be noted that the use of plasma colloids or vasopressor agents is allowed to achieve the maintenance of blood pressure.
* Current participation in another experimental treatment protocol.

Primary outcomes:
measure: Clinically Significant Treatment Emergent Events
timeFrame: From first dose up until Day 28
measure: All Cause Mortality at Day 28
timeFrame: 28 days following commencement of therapy
Secondary outcomes:
measure: All Cause Mortality Rate at 6 Months
timeFrame: 6 months following commencement of therapy
Other outcomes:
Locations:
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Edinburgh
country: United Kingdom
facility: Edinburgh Royal Infirmary
city: Glasgow
country: United Kingdom
facility: Western Infirmary
city: Glasgow
country: United Kingdom
facility: Victoria Infirmary
city: London
country: United Kingdom
facility: Whittington Hospital
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: St Thomas' Hospital
city: London
country: United Kingdom
facility: St Mary's Hospital
Study officials:
affiliation: University College London Hospital
name: Geoff Bellingan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Whittington Hospital
name: Martin Kuper, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St Mary's Hospital, London
name: Martin Stotz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St Thomas' Hospital
name: Richard Beale, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital of Wales
name: Mathew Wise, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Western Infirmary
name: Alexander Binning, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Victoria Infirmary
name: Alan Davidson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Edinburgh Royal Infirmary
name: Timothy Walsh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kiss J, Yegutkin GG, Koskinen K, Savunen T, Jalkanen S, Salmi M. IFN-beta protects from vascular leakage via up-regulation of CD73. Eur J Immunol. 2007 Dec;37(12):3334-8. doi: 10.1002/eji.200737793.
citation: Bellingan G, Maksimow M, Howell DC, Stotz M, Beale R, Beatty M, Walsh T, Binning A, Davidson A, Kuper M, Shah S, Cooper J, Waris M, Yegutkin GG, Jalkanen J, Salmi M, Piippo I, Jalkanen M, Montgomery H, Jalkanen S. The effect of intravenous interferon-beta-1a (FP-1201) on lung CD73 expression and on acute respiratory distress syndrome mortality: an open-label study. Lancet Respir Med. 2014 Feb;2(2):98-107. doi: 10.1016/S2213-2600(13)70259-5. Epub 2013 Dec 23.