E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of Multi-Organ Failure on Patients Surviving Open Surgery for a Ruptured Abdominal Aortic Aneurysm. |
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E.1.1.1 | Medical condition in easily understood language |
Post-surgical preventive treatment of patients after emergency surgery for a ruptured abdominal aortic aneurysm. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028154 |
E.1.2 | Term | Multi-organ failure |
E.1.2 | System Organ Class | 100000004867 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy and safety of FP-1201-lyo over placebo on all-cause mortality at study day 30; D30 . |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of FP-1201-lyo treatment by assessing short term outcomes (D30) and midterm outcomes (D90 [3 months]) 2. To evaluate the safety and tolerability of FP-1201-lyo treatment 3. To evaluate the pharmacodynamics (PD) of FP-1201-lyo 4. To evaluate the Tentative Disease Specific Marker CD73 and Potential Inflammatory Markers (PIM) 5. To evaluate neutralizing antibodies against IFN beta-1a (NAbs) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for inclusion into this study, each patient must fulfil the following inclusion criteria during screening and prior to the first dose of study medication being administered on D0 (criteria 1 or 2 and all 3, 4 and 5): 1. Patients (male or female) presenting with a ruptured abdominal aortic aneurysm (RAAA) diagnosed by ultrasound or CT-scan in the emergency room • all forms of infrarenal RAAAs with or without coexisting iliac aneurysms are included or 2. Patients (male or female) presenting with symptoms of RAAA known to have an infrarenal AAA and proceeding straight to open repair without radiological assessment and confirmed rupture (=retroperitoneal haematoma) in operation and 3. Aneurysma repair must be infra-renal, i.e. the proximal anastomosis must be below the renal arteries and the renal arteries have to stay intact. Temporary above the renal clamping can be used for a maximum of 30 minutes (total clamping time) and 4. Patients or their next of kin providing informed consent (written signed or witnessed) and 5. Age of 18 years or higher |
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E.4 | Principal exclusion criteria |
To be eligible for inclusion into this study, each patient must not meet any of the following exclusion criteria during screening or prior to the first dose of study medication being administered: 1. Moribund patient not eligible for treatment in ICU or expected to survive surgery 2. Markedly short life expectancy, e.g. advanced malignant disease 3. Current participation in another experimental treatment protocol 4. Significant congestive heart failure, defined as New York Heart Association (NYHA) class IV 5. Current treatment with IFN alpha or IFN beta 6. Dialysis therapy for chronic renal failure 7. Irreversible shock from haemorrhage 8. Unconsciousness when arriving to the hospital and during screening 9. rEVAR first (prior attempt for endovascular aortic repair for the current rupture) 10. Diagnosed cirrhosis 11. Pregnancy and women with child bearing potential without negative pregnancy test 12. Rupture not confirmed by CT or intra-operatively (impending ruptures are excluded) 13. RAAA requiring repair of the renal arteries or the proximal aorta • thoracoabdominal aneurysms requiring immediate repair • damaged renal arteries during emergency clamping requiring repair NOTE: • temporary clamping above the renal arteries (max 30 min total clamping time above the renal arteries) does not lead to exclusion • ligation of the left renal vein does not lead to exclusion
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Efficacy Endpoint: • All cause mortality at D30
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints: • All cause mortality at D90 (3 months) • Number of ventilator free days (VFDs) at D30 • Number of days receiving haemodialysis at D30 and D90 • Number of organ failure free days up to D30 by means of the SOFA score • Prevalence of abdominal compartment syndrome, i.e. intra-abdominal pressure (IAP) between study groups • Neutralizing antibodies against IFN beta-1a (NAbs) in whole blood samples up to D30 • Disability on D90 measured by modified ranking scale (mRS)
Safety: • Clinically significant treatment emergent adverse events (TEAEs) up to D30 from vital signs data, laboratory data, physical examinations and spontaneous reporting when conscious
Pharmacoeconomics: • Length of ICU stay, in terms of ICU free days at D30 • Length of hospital stay, in terms of hospital free days at D90 • Length of stay at another health care facility at D90 • Length of haemodialysis needed • Ventilation free days at D30
Pharmacodynamics (PD): • MxA (protein) concentration in whole blood samples from baseline up to D13
Tentative Disease Specific Marker: • CD73 concentration/activity in serum samples from baseline up to D13 • Potential Inflammatory Markers (IL-6 and HGF) in serum samples from baseline up to D13
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Days 0-13, Day 30, Day 90 |
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tentative disease specific markers |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 4 |