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

• Sponsor: Faron Pharmaceuticals Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00789685
• Collaborator: (none)
• Enrollment: 37
• Locations: 8
• Arm: 1
• Duration (Months): 30.9
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Lung Injury; Acute Respiratory Distress Syndrome	Drug: Interferon Beta	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Feb 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Interferon Beta Interferon Beta	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.; Other Names: FP-1201 IFN-beta

Outcome Measures

Primary Outcome Measures

1. Clinically Significant Treatment Emergent Events [From first dose up until Day 28]

   Treatment-emergent adverse events (TEAEs) in safety population

2. 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 Outcome Measures

1. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital of Wales	Cardiff		United Kingdom	CG14 4XW
2	Edinburgh Royal Infirmary	Edinburgh		United Kingdom	EH16 4SA
3	Western Infirmary	Glasgow		United Kingdom	G11 6NT
4	Victoria Infirmary	Glasgow		United Kingdom	G42 9TY
5	Whittington Hospital	London		United Kingdom	N19 5NF
6	University College London Hospital	London		United Kingdom	NW1 2BU
7	St Thomas' Hospital	London		United Kingdom	SE1 7EH
8	St Mary's Hospital	London		United Kingdom	W2 1NY

Sponsors and Collaborators

• Faron Pharmaceuticals Ltd

Investigators

• Principal Investigator: Geoff Bellingan, MD, University College London Hospital
• Principal Investigator: Martin Kuper, MD, Whittington Hospital
• Principal Investigator: Martin Stotz, MD, St Mary's Hospital, London
• Principal Investigator: Richard Beale, MD, St Thomas' Hospital
• Principal Investigator: Mathew Wise, MD, University Hospital of Wales
• Principal Investigator: Alexander Binning, MD, Western Infirmary
• Principal Investigator: Alan Davidson, MD, Victoria Infirmary
• Principal Investigator: Timothy Walsh, MD, Edinburgh Royal Infirmary

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Sponsor's website

Publications

• 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.

• Responsible Party: Faron Pharmaceuticals Ltd
• ClinicalTrials.gov Identifier: NCT00789685
• Other Study ID Numbers: FPCLI001
• First Posted: Nov 13, 2008
• Last Update Posted: May 27, 2015
• Last Verified: May 1, 2015

• Keywords provided by Faron Pharmaceuticals Ltd: Open label
• Additional relevant MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Syndrome; Interferons; Interferon-beta

Study Results

Participant Flow

Arm/Group Title	Interferon Beta
Arm/Group Description	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.
Period Title: Overall Study
STARTED	37
COMPLETED	25
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Safety Population
Arm/Group Description	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
Overall Participants	37
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	52.6
Sex: Female, Male (Count of Participants)
Female	15 40.5%
Male	22 59.5%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	31 83.8%
Black or African	3 8.1%
South American	1 2.7%
Asian	2 5.4%
Region of Enrollment (participants) [Number]
United Kingdom	37 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Patients included in Safety population

Arm/Group Title	Safety Population
Arm/Group Description	Safety population includes all patients who received at least one dose of study medication
Measure Participants	37
TEAEs	37
Severe TEAEs	30
Serious TEAEs	22
Drug-Related TEAEs	20
Serious Drug-Related TEAEs	8
TEAEs leading to withdrawal	6

2. Primary Outcome

Title	All Cause Mortality at Day 28
Description	The primary efficacy variable was all cause mortality at Day 28 following commencement of treatment
Time Frame	28 days following commencement of therapy

Outcome Measure Data

Analysis Population Description

Patients included in Safety population

Arm/Group Title	Safety Population
Arm/Group Description	Safety population includes all patients who received at least one dose of study medication
Measure Participants	37
Number [percentage of patients who died]	8.1

3. Secondary Outcome

Title	All Cause Mortality Rate at 6 Months
Description	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

Outcome Measure Data

Analysis Population Description

Number of patients whose survival status at 6 months was known

Arm/Group Title	Safety Population
Arm/Group Description	Safety population includes all patients who received at least one dose of study medication
Measure Participants	36
Number [percentage of patients who died]	11.1

Adverse Events

Time Frame	Over the course of the study (Days 1 - 28) and at withdrawal
Adverse Event Reporting Description	Adverse Events (AEs) were reviewed and documented from the time the first dose was given up until Day 28. AEs were also reviewed and documented at the withdrawal visit.
Arm/Group Title	Safety Population
Arm/Group Description	Safety population includes all patients who received at least one dose of study medication
All Cause Mortality
	Safety Population
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Safety Population
	Affected / at Risk (%)	# Events
Total	22/37 (59.5%)
Blood and lymphatic system disorders
Thrombocytosis	1/37 (2.7%)	1
Anaemia	3/37 (8.1%)	4
Hyperbilirubinaemia	1/37 (2.7%)	1
Cardiac disorders
Cardiopulmonary Failure	1/37 (2.7%)	1
Cardiac Arrest	2/37 (5.4%)	4
Pericardial Effusion	1/37 (2.7%)	1
Sinus Tachycardia	1/37 (2.7%)	2
Cardio-Respiratory Arrest	1/37 (2.7%)	1
General disorders
Pyrexia	1/37 (2.7%)	1
Chills	1/37 (2.7%)	2
Multi-Organ Failure	2/37 (5.4%)	2
Hepatobiliary disorders
Cholecystitis Acute	1/37 (2.7%)	1
Hepatic Function Abnormal	1/37 (2.7%)	1
Immune system disorders
Hypersensitivity	1/37 (2.7%)	1
Infections and infestations
Sepsis	1/37 (2.7%)	2
Lower Respiratory Tract Infection	1/37 (2.7%)	1
Klebsiella Sepsis	1/37 (2.7%)	1
Clostridial Infection	1/37 (2.7%)	1
Septic Shock	1/37 (2.7%)	1
Respiratory Tract Infection	1/37 (2.7%)	1
Injury, poisoning and procedural complications
Subdural Haematoma	1/37 (2.7%)	1
Investigations
Haemoglobin Decreased	2/37 (5.4%)	2
Blood Creatine Phosphokinase Increased	1/37 (2.7%)	1
Alanine Aminotransferase Increased	1/37 (2.7%)	1
Platelet Count Decreased	1/37 (2.7%)	1
Metabolism and nutrition disorders
Hypernatraemia	3/37 (8.1%)	3
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	1/37 (2.7%)	1
Pulmonary Oedema	1/37 (2.7%)	1
Other (Not Including Serious) Adverse Events
	Safety Population
	Affected / at Risk (%)	# Events
Total	37/37 (100%)
Blood and lymphatic system disorders
Anaemia	4/37 (10.8%)	6
Thrombocytosis	1/37 (2.7%)	1
Disseminated Intravascular Coagulation	1/37 (2.7%)	1
Thrombocytopenia	1/37 (2.7%)	1
Cardiac disorders
Tachycardia	4/37 (10.8%)	8
Atrial Fibrillation	4/37 (10.8%)	4
Arrhythmia	1/37 (2.7%)	1
Bradycardia	1/37 (2.7%)	1
Right Ventricular Hypertrophy	1/37 (2.7%)	1
Ear and labyrinth disorders
Deafness Unilateral	1/37 (2.7%)	1
Eye disorders
Herpes Simplex Ophthalmic	1/37 (2.7%)	1
Vitreous Floaters	1/37 (2.7%)	1
Gastrointestinal disorders
Diarrhoea	9/37 (24.3%)	11
Constipation	9/37 (24.3%)	10
Mouth Ulceration	3/37 (8.1%)	3
Nausea	3/37 (8.1%)	3
Abdominal distension	2/37 (5.4%)	2
Vomiting	2/37 (5.4%)	2
Abdominal pain	1/37 (2.7%)	1
Faecal volume increased	1/37 (2.7%)	1
Gastrooesophageal reflux disease	1/37 (2.7%)	1
Haematochezia	1/37 (2.7%)	1
Large intestinal obstruction	1/37 (2.7%)	1
Oral pain	1/37 (2.7%)	1
General disorders
Pyrexia	11/37 (29.7%)	17
Hyperpyrexia	2/37 (5.4%)	2
Pain	2/37 (5.4%)	2
Fatigue	1/37 (2.7%)	1
Generalised Oedema	1/37 (2.7%)	1
Influenza Like Illness	1/37 (2.7%)	1
Immune system disorders
Cytokine Release Syndrome	1/37 (2.7%)	3
Infections and infestations
Candidiasis	4/37 (10.8%)	5
Clostridial Infection	3/37 (8.1%)	3
Cellulitis	3/37 (8.1%)	3
Sepsis	1/37 (2.7%)	1
Oral Candidiasis	2/37 (5.4%)	2
Staphylococcal Infection	1/37 (2.7%)	2
Abdominal Sepsis	1/37 (2.7%)	1
Bacterial Infection	1/37 (2.7%)	1
Empyema	1/37 (2.7%)	1
Escherichia Bacteraemia	1/37 (2.7%)	1
Escherichia Infection	1/37 (2.7%)	1
Infection	1/37 (2.7%)	1
Klebsiella Infection	1/37 (2.7%)	1
Lung Infection Pseudomonal	1/37 (2.7%)	1
Pneumonia	1/37 (2.7%)	1
Pneumonia Cytomegaloviral	1/37 (2.7%)	1
Salmonellosis	1/37 (2.7%)	1
Urinary Tract Infection Fungal	1/37 (2.7%)	1
Wound Infection	1/37 (2.7%)	1
Injury, poisoning and procedural complications
Collapse of Lung	1/37 (2.7%)	1
Gastrointestinal Stoma Complication	1/37 (2.7%)	1
Procedural Pain	1/37 (2.7%)	1
Subcutaneous Emphysema	1/37 (2.7%)	1
Investigations
Haemoglobin Decreased	12/37 (32.4%)	22
Electrocardiogram T Wave Inversion	2/37 (5.4%)	2
Nasogastric Output High	2/37 (5.4%)	2
Blood Lactate Dehydrogenase Increased	1/37 (2.7%)	1
Blood Sodium Increased	1/37 (2.7%)	1
Electrocardiogram QT Prolonged	1/37 (2.7%)	1
Oxygen Saturation Decreased	1/37 (2.7%)	1
Troponin T Increased	1/37 (2.7%)	1
Metabolism and nutrition disorders
Hypernatraemia	4/37 (10.8%)	6
Oedema Peripheral	3/37 (8.1%)	3
Hypokalaemia	2/37 (5.4%)	2
Acidosis	1/37 (2.7%)	1
Alkalosis	1/37 (2.7%)	1
Hyperkalaemia	1/37 (2.7%)	1
Hyperlipidaemia	1/37 (2.7%)	1
Metabolic Alkalosis	1/37 (2.7%)	1
Musculoskeletal and connective tissue disorders
Critical Illness Polyneuropathy	2/37 (5.4%)	2
Rib Fracture	1/37 (2.7%)	1
Nervous system disorders
Headache	2/37 (5.4%)	2
Convulsion	1/37 (2.7%)	1
Partial Seizures	1/37 (2.7%)	1
Peroneal Nerve Palsy	1/37 (2.7%)	1
Tremor	1/37 (2.7%)	1
Psychiatric disorders
Insomnia	10/37 (27%)	11
Agitation	5/37 (13.5%)	6
Confusional State	4/37 (10.8%)	5
Delirium	4/37 (10.8%)	4
Anxiety	2/37 (5.4%)	2
Depression	1/37 (2.7%)	1
Post-Traumatic Stress Disorder	1/37 (2.7%)	1
Renal and urinary disorders
Renal Impairment	4/37 (10.8%)	6
Polyuria	1/37 (2.7%)	1
Renal Failure	1/37 (2.7%)	1
Renal Pain	1/37 (2.7%)	1
Reproductive system and breast disorders
Genital Swelling	1/37 (2.7%)	1
Menorrhagia	1/37 (2.7%)	1
Penile Oedema	1/37 (2.7%)	1
Scrotal Oedema	1/37 (2.7%)	1
Scrotal Swelling	1/37 (2.7%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	2/37 (5.4%)	3
Pulmonary Oedema	2/37 (5.4%)	2
Pneumothorax	2/37 (5.4%)	2
Aspiration	1/37 (2.7%)	1
Hiccups	1/37 (2.7%)	1
Hypoxia	1/37 (2.7%)	1
Increased Bronchial Secretion	1/37 (2.7%)	1
Oropharyngeal Pain	1/37 (2.7%)	1
Pulmonary Cavitation	1/37 (2.7%)	1
Respiratory Gas Exchange Disorder	1/37 (2.7%)	1
Skin and subcutaneous tissue disorders
Decubitus Ulcer	9/37 (24.3%)	35
Erythema	1/37 (2.7%)	1
Rash	1/37 (2.7%)	1
Skin Ulcer	1/37 (2.7%)	1
Vascular disorders
Hypertension	2/37 (5.4%)	7
Haemorrhage	2/37 (5.4%)	2
Post Procedural Haemorrhage	2/37 (5.4%)	2
Cerebral Infarction	1/37 (2.7%)	1
Deep Vein Thrombosis	1/37 (2.7%)	1
Extremity Necrosis	1/37 (2.7%)	1
Vasculitis	1/37 (2.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Review by sponsor of related publication & communications