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Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Prevention of Multi-Organ Failure on Patients After Open Surgery for a RAAA (INFORAAA)

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ClinicalTrials.gov Identifier: NCT03119701
Recruitment Status : Terminated (IDMC recommendation. Unexpectedly high use of concomitant corticosteroid treatment.)
First Posted : April 19, 2017
Results First Posted : January 14, 2021
Last Update Posted : January 14, 2021
Sponsor:
Information provided by (Responsible Party):
Faron Pharmaceuticals Ltd

Tracking Information
First Submitted Date  ICMJE March 3, 2017
First Posted Date  ICMJE April 19, 2017
Results First Submitted Date  ICMJE September 22, 2020
Results First Posted Date  ICMJE January 14, 2021
Last Update Posted Date January 14, 2021
Actual Study Start Date  ICMJE February 18, 2017
Actual Primary Completion Date September 23, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 13, 2017)
The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality [ Time Frame: Day 30 ]
Number of fatalities
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 22, 2020)
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality [ Time Frame: Day 90 ]
    Number of fatalities
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs) [ Time Frame: Day 30 ]
    Number of ventilator free days. VFDs to Day 30 were defined as the number of calendar days after initiating unassisted breathing (UAB) to Day 30 from first treatment, assuming that a patient survives at least 48 consecutive hours after initiating UAB. Patients who die without initiating UAB were assigned a VFD value of zero.
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis [ Time Frame: Day 30 and Day 90 ]
    Number of days receiving hemodialysis. There were only few reported values other than zero.
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Organ Failure Free Days by Means of the Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: Day 30 ]
    Organ failure free days were defined as the number of days in the first 30 days after the first dose of study medication that the patient was alive and free of organ failure with a SOFA score of zero for the following six organ parameters: respiration, coagulation, liver, cardiovascular, central nervous system and renal function. It is graded from 0 to 4 according to the degree of dysfunction/ failure (higher scores indicate more severe organ failure). Patients who died without achieving a SOFA score of zero was assigned an organ failure free days value of zero. Note: the information for organ failure free days has been only collected when the patients have been in the Intensive Care Unit (ICU). As ICU free days have been reported in a separate variable, it was decided that presented information will be kept, without trying to conduct imputation.
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) [ Time Frame: Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay ]
    Intra-abdominal pressure values, which were routinely measured during ICU stay via urine bladder catheter.
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples [ Time Frame: Day 30 ]
    IFN beta-1a neutralizing antibodies immune response. Blood samples for the NAbs assessments were collected at Day 0 pre-dose (baseline) and at Day 30.
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). [ Time Frame: Day 90 ]
    Scale gives the degree of disability or dependence in the daily activities. Single mRS value is applied for every patient based on patient or caregiver interview. The scale runs from 0-6, from perfect health without symptoms to death. Pre-operation Baseline Visit mRS value is collected for reference.
  • Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters [ Time Frame: Day 0 to Day 30 ]
    Number of TEAEs from vital signs data, laboratory data, physical examinations and spontaneous reporting when conscious.
  • Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days [ Time Frame: Day 30 or Day 90 ]
    Economic measurement:
    • 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
    • The number of days on hemodialysis at D30 and at D90
    • The number of organ failure free days at D30
    • The number of ventilation free days at D30
Original Secondary Outcome Measures  ICMJE
 (submitted: April 13, 2017)
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality [ Time Frame: Day 90 ]
    Number of fatalities
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs) [ Time Frame: Day 30 ]
    Number of ventilator free days
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis [ Time Frame: Day 30 and Day 90 ]
    Number of days receiving hemodialysis
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Organ Failure Free Days by Means of the Sequential Organ Failure Assessment (SOFA) Score [ Time Frame: Day 30 ]
    Number of organ failure free days
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) [ Time Frame: Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay ]
    Intra-abdominal pressure values
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples [ Time Frame: Day 30 ]
    IFN beta-1a neutralizing antibodies immune response
  • The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). [ Time Frame: Day 90 ]
    Scale gives the degree of disability or dependence in the daily activities
  • Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters [ Time Frame: Day 0 to Day 30 ]
    Number of treatment emergent adverse events and serious adverse reactions, information of blood pressure, hart rates and temperature,and clinical laboratory parameters for biochemistry and haematology
  • Pharmacoeconomic Information of Length of ICU Stay, Length of Hospital Stay, Length of Stay at Another Health Care Facility, Length of Hemodialysis Needed, Ventilation Free Days [ Time Frame: Day 30 or Day 90 ]
    Economic measurement
Current Other Pre-specified Outcome Measures
 (submitted: December 22, 2020)
  • Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker [ Time Frame: Day 0 up to Day 13 ]
    Concentration of Myxovirus Resistant Protein A (MxA)
  • Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples [ Time Frame: Day 0 up to Day 13 ]
    CD73 (ecto-5'-nucleotidase enzyme) concentration
  • Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples [ Time Frame: Day 0 up to Day 13 ]
    IL-6 concentration.
  • Tentative Disease Specific, Potential Inflammatory Marker - Hepatocyte Growth Factor [HGF]) in Serum Samples [ Time Frame: Day 0 up to Day 13 ]
    HGF concentration.
Original Other Pre-specified Outcome Measures
 (submitted: April 13, 2017)
  • Pharmacodynamic marker by Myxovirus Resistant Protein A (MxA) concentration in whole blood samples [ Time Frame: Day 0 up to Day 13 ]
    Concentration of Myxovirus Resistant Protein A (MxA)
  • Tentative Disease Specific Marker CD73 (ecto-5'-nucleotidase enzyme ) concentration in serum samples [ Time Frame: Day 0 up to Day 13 ]
    CD73 (ecto-5'-nucleotidase enzyme ) concentration
  • Tentative Disease Specific, Potential Inflammatory Markers [Interleukin 6 (IL-6) and Hepatocyte growth factor (HGF)] in serum samples [ Time Frame: Day 0 up to Day 13 ]
    Measurement of Inflammatory Markers (IL-6 and HGF)
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Prevention of Multi-Organ Failure on Patients After Open Surgery for a RAAA
Official Title  ICMJE A Randomised, Parallel Group 2:1 Comparison of the Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) and Placebo in the Prevention of Multi-Organ Failure on Patients Surviving Open Surgery for a Ruptured Abdominal Aortic Aneurysm
Brief Summary A study to assess effectiveness and safety of a drug FP-1201-lyo (Recombinant Human Interferon Beta-1a) in the Prevention of Multi-Organ Failure on patients after Open Surgery for a Ruptured Abdominal Aortic Aneurysm
Detailed Description

This trial is multicentre, randomised, double-blinded, Phase II, parallel group comparison study of the efficacy and safety of FP-1201-lyo compared to placebo in patients surviving emergency open surgery for an infra-renal ruptured abdominal aortic aneurysm. Investigational medicinal product will be administered as post-surgical preventive treatment either 10µg FP-1201-lyo or placebo. Treatment will be administered daily every 24 hrs for 6 days. The first dose will be given after successful surgery at the point when the patient arrives to the Intensive Care Unit (ICU).

Both treatment groups will receive standard supportive care.

Aim is randomise and initiate treatment of 152 patients. For the final analysis, a minimum of 129 evaluable patients will be required.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Multicentre, randomised, double-blinded, Phase II, parallel group comparison study of the efficacy and safety of FP-1201-lyo compared to placebo in patients surviving emergency open surgery for an infra-renal ruptured abdominal aortic aneurysm.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Preventive Medicine
  • Multi Organ Failure
Intervention  ICMJE
  • Drug: Interferon Beta-1A
    Lyophilisate for solution for injection.
    Other Names:
    • FP-1201-lyo
    • ATC code L03AB07
  • Drug: Placebo
    Lyophilisate for solution for injection as placebo.
    Other Name: Placebo for investigational drug
Study Arms  ICMJE
  • Experimental: FP-1201-lyo 10 µg

    FP-12-lyo 10 µg (Interferon Beta-1a) will be administered once daily as an intravenous bolus injection for 6 days.

    Investigational product is lyophilisate for solution for injection which will be reconstituted in water for injection.

    Intervention: Drug: Interferon Beta-1A
  • Placebo Comparator: FP-1201-lyo Placebo

    FP-1201-lyo Placebo will be administered once daily as an intravenous bolus injection for 6 days.

    Investigational placebo is lyophilisate for solution for injection which will be reconstituted in water for injection

    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 5, 2019)
40
Original Estimated Enrollment  ICMJE
 (submitted: April 13, 2017)
152
Actual Study Completion Date  ICMJE October 3, 2019
Actual Primary Completion Date September 23, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 providing informed consent

    and

  5. Age of 18 years or higher

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 Interferon (IFN) alpha or IFN beta
  6. Dialysis therapy for chronic renal failure
  7. Irreversible shock from haemorrhage
  8. Unconsciousness or inability to give consent
  9. Ruptured Endovascular Aortic Repair (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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Estonia,   Finland,   Lithuania
Removed Location Countries United Kingdom
 
Administrative Information
NCT Number  ICMJE NCT03119701
Other Study ID Numbers  ICMJE FP1CLI006
2014-000899-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Faron Pharmaceuticals Ltd
Study Sponsor  ICMJE Faron Pharmaceuticals Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Harri Hakovirta, MD Turku University Hospital
Principal Investigator: Maarit Venermo, MD Helsinki University Central Hospital
PRS Account Faron Pharmaceuticals Ltd
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP