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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Acute Lung Injury, Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: Interferon Beta


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interferon Beta<br>Interferon Beta | Drug: Interferon Beta<br>* 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.<br>* Other names: IFN-beta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically Significant Treatment Emergent Events | Treatment-emergent adverse events (TEAEs) in safety population | From first dose up until Day 28 | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Open label