Acute Lung Injury, Acute Respiratory Distress Syndrome
Conditions
Keywords
Open label
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.
Interventions
DRUGInterferon 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.
Sponsors
Faron Pharmaceuticals Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinically Significant Treatment Emergent Events | From first dose up until Day 28 | Treatment-emergent adverse events (TEAEs) in safety population |
| All Cause Mortality at Day 28 | 28 days following commencement of therapy | The primary efficacy variable was all cause mortality at Day 28 following commencement of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Cause Mortality Rate at 6 Months | 6 months following commencement of therapy | A long-term secondary efficacy variable was all cause mortality at 6 months following commencement of treatment |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Safety Population Safety population includes all patients who received at least one dose of study medication, and was used for summaries of demographic and other baseline characteristics | 37 |
| Total | 37 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 52.6 years |
| Race/Ethnicity, Customized Asian | 2 participants |
| Race/Ethnicity, Customized Black or African | 3 participants |
| Race/Ethnicity, Customized Caucasian | 31 participants |
| Race/Ethnicity, Customized South American | 1 participants |
| Region of Enrollment United Kingdom | 37 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 37 / 37 |
| serious Total, serious adverse events | 22 / 37 |
Outcome results
Primary
All Cause Mortality at Day 28
The primary efficacy variable was all cause mortality at Day 28 following commencement of treatment
Time frame: 28 days following commencement of therapy
Population: Patients included in Safety population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Population | All Cause Mortality at Day 28 | 8.1 percentage of patients who died |
Primary
Clinically Significant Treatment Emergent Events
Treatment-emergent adverse events (TEAEs) in safety population
Time frame: From first dose up until Day 28
Population: Patients included in Safety population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Safety Population | Clinically Significant Treatment Emergent Events | Severe TEAEs | 30 Number of patients |
| Safety Population | Clinically Significant Treatment Emergent Events | TEAEs | 37 Number of patients |
| Safety Population | Clinically Significant Treatment Emergent Events | Serious TEAEs | 22 Number of patients |
| Safety Population | Clinically Significant Treatment Emergent Events | Drug-Related TEAEs | 20 Number of patients |
| Safety Population | Clinically Significant Treatment Emergent Events | Serious Drug-Related TEAEs | 8 Number of patients |
| Safety Population | Clinically Significant Treatment Emergent Events | TEAEs leading to withdrawal | 6 Number of patients |
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
Time frame: 6 months following commencement of therapy
Population: Number of patients whose survival status at 6 months was known
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Safety Population | All Cause Mortality Rate at 6 Months | 11.1 percentage of patients who died |