Safety, Tolerability and Preliminary Efficacy of FP-1201 in ALI and ARDS. Phase I/II

Acute Respiratory Distress Syndrome Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00789685
• Other study ID #: FPCLI001
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: November 11, 2008
• Last updated: May 11, 2015
• Start date: February 2009
• Est. completion date: September 2011

Study information

• Verified date: May 2015
• Source: Faron Pharmaceuticals Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Lung Injury
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• Interferon Beta
Interferon Beta administered intravenously daily for 6 days. Doses of 0.12 MIU, 1.2 MIU, 2.7 MIU or 6.0 MIU (dose escalation phase) or 2.7 MIU (dose expansion phase) were administered.

Locations

Country	Name	City	State
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Edinburgh Royal Infirmary	Edinburgh
United Kingdom	Victoria Infirmary	Glasgow
United Kingdom	Western Infirmary	Glasgow
United Kingdom	St Mary's Hospital	London
United Kingdom	St Thomas' Hospital	London
United Kingdom	University College London Hospital	London
United Kingdom	Whittington Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Faron Pharmaceuticals Ltd

Country where clinical trial is conducted

United Kingdom, 

References & Publications (2)

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 — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinically Significant Treatment Emergent Events	Treatment-emergent adverse events (TEAEs) in safety population	From first dose up until Day 28	Yes
Primary	All Cause Mortality at Day 28	The primary efficacy variable was all cause mortality at Day 28 following commencement of treatment	28 days following commencement of therapy	Yes
Secondary	All Cause Mortality Rate at 6 Months	A long-term secondary efficacy variable was all cause mortality at 6 months following commencement of treatment	6 months following commencement of therapy	Yes

External Links

•   Sponsor's website