E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS) |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of FP-1201 in patients with ALI/ARDS
To assess the safety, tolerability and preliminary efficacy of the Optimum tolerated dose in patients likely to derive clinical benefit
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E.2.2 | Secondary objectives of the trial |
To establish appropriate dose(s) of FP-1201 for use in future studies of patients with ALI/ARDS.
To determine the pharmacokinetics (PK) of FP-1201 when administered intravenously daily as a single injection for a maximum of 6 days, to patients with ALI/ARDS.
To demonstrate the pharmacodynamic activity of FP-1201 in patients with ALI/ARDS.
To assess for evidence of neutralizing antibodies to interferon beta in patients with ALI/ARDS.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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: Pa02 /Fi02 ratio ≤ 300 in a stable state after the patient has adapted to standardised ventilation.(Within the UK this equates to <40 kPa) •ARDS: Pa02 /Fi02 ≤ 200 in a stable state after the patient has adapted to standardised ventilation.(Within the UK this equates to <26.7 kPa)
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
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E.4 | Principal exclusion criteria |
Patients with burns
Women known to be pregnant, lactating or having a positive or indeterminate pregnancy test.
Patients with significant COPD 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 immumodulatory 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Safety Endpoints:
Clinically significant treatment emergent adverse events, physical examination. Vital signs (i.e. Blood Pressure (BP) and heart rate (P/R) electrocardiogram (ECG) and laboratory finding including clinical chemistry, haematology and urinalysis.
2. Efficacy Endpoints:
Primary Endpoint.
Measurable objective response criteria All cause mortality at Day 28 following the commencement of FP-1201 therapy.
Secondary Endpoints to be analysed at Day 28 following the commencement of FP-1201 therapy:
Days alive and off ventilation Days on ITU (or up to the point when patient is ready for discharge from ITU) Days on vaso-active drugs Frequency of complications such as neck/thoracic, gastrointestinal, cardiac, haemodynamic, vascular or barotrauma.
Short-term Secondary Endpoints:
Changes in Pa02 /Fi02 ratio, and other relevant lung parameters during mechanical ventilation. Time to the development/resolution of clinically significant organ dysfunction e.g. renal, hepatic, haematological, and cardiovascular.
Long-term Secondary Endpoints:
All cause mortality rate at six months following the commencement of FP-1201 therapy.
3. Pharmacokinetic and Pharmacodynamic Endpoints:
Serum levels of Interferon-Beta will be measured to characterise the pharmacokinetics of FP-1201 in ALI/ARDS patients.
The effects of FP-1201 on pharmacodynamic endpoints will be determined in blood samples measuring the following biomarkers:
- CD73 activity from serum samples - MxA concentration and MxA mRNA levels as measured from plasma samples - Pro-collagen III N-terminal peptide concentrations from serum samples - Biological markers in serum known to be affected by IFN treatment in patients with multiple sclerosis: a. β2 – macroglobulin concentration b. Neopterin concentration
The presence of neutralizing antibodies to Interferon-Beta will also be determined.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
First administration to ALI/ARDS patients |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |