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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions Preventive Medicine
Multi Organ Failure
Interventions Drug: Interferon Beta-1A
Drug: Placebo
Enrollment 40
Recruitment Details  
Pre-assignment Details  
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Period Title: 6-day Dosing
Started 29 11
Completed 22 8
Not Completed 7 3
Reason Not Completed
Death             4             1
Adverse Event             3             0
Physician Decision             0             1
Withdrawal by Subject             0             1
Period Title: Mid-term (Final) Follow-up at D90
Started 25 [1] 10 [2]
Completed 22 9
Not Completed 3 1
Reason Not Completed
Death             3             1
[1]
3 patients who discontinued study drug due to adverse events were also followed up.
[2]
2 patients who did not receive 6 doses were also followed up.
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo Total
Hide Arm/Group Description

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for Investigational drug.

Total of all reporting groups
Overall Number of Baseline Participants 27 11 38
Hide Baseline Analysis Population Description
A total of 40 subjects received at least 1 dose of study drug. 2 patients were excluded from Full Analysis Set for Efficacy (FAS-E) and Per Protocol Set (PPS) populations due to early deaths (within 36 hours from first dose of the study treatment). Therefore, FAS-E and PPS populations consisted of 38 patients.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 11 participants 38 participants
< 70 years
7
  25.9%
3
  27.3%
10
  26.3%
70-80 years
14
  51.9%
6
  54.5%
20
  52.6%
> 80 years
6
  22.2%
2
  18.2%
8
  21.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 11 participants 38 participants
Female
4
  14.8%
0
   0.0%
4
  10.5%
Male
23
  85.2%
11
 100.0%
34
  89.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 11 participants 38 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
27
 100.0%
11
 100.0%
38
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 27 participants 11 participants 38 participants
Finland 23 8 31
Lithuania 3 1 4
Estonia 1 2 3
Baseline Height  
Mean (Standard Deviation)
Unit of measure:  Centimetres
Number Analyzed 27 participants 11 participants 38 participants
172.3  (6.34) 177.5  (7.59) 173.8  (7.05)
Baseline Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 27 participants 11 participants 38 participants
82.0  (16.14) 95.9  (21.21) 86.0  (18.58)
1.Primary Outcome
Title The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Hide Description Number of fatalities
Time Frame Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 27 11
Measure Type: Count of Participants
Unit of Measure: Participants
6
  22.2%
2
  18.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.78
Comments The threshold for statistical significance was p = 0.05.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.30
Confidence Interval (2-Sided) 95%
0.21 to 8.19
Estimation Comments [Not Specified]
2.Secondary Outcome
Title The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Hide Description Number of fatalities
Time Frame Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 27 11
Measure Type: Count of Participants
Unit of Measure: Participants
7
  25.9%
2
  18.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.57
Comments The threshold for statistical significance was p = 0.05.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.7
Confidence Interval (2-Sided) 95%
0.28 to 10.52
Estimation Comments [Not Specified]
3.Secondary Outcome
Title The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs)
Hide Description 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.
Time Frame Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 27 11
Median (Full Range)
Unit of Measure: days
25.0
(0.0 to 30.0)
29.0
(0.0 to 29.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.08
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Secondary Outcome
Title The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis
Hide Description Number of days receiving hemodialysis. There were only few reported values other than zero.
Time Frame Day 30 and Day 90
Hide Outcome Measure Data
Hide Analysis Population Description

The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).

The overall number of participants analyzed reflects the number of patients that had sufficient data to allow for calculation of the outcome measure.

Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 21 9
Mean (Standard Deviation)
Unit of Measure: days
Day 30 Number Analyzed 21 participants 9 participants
0.9  (4.15) 0.0  (0.00)
Day 90 Number Analyzed 20 participants 9 participants
0.6  (2.68) 0.0  (0.00)
5.Secondary Outcome
Title 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
Hide Description

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.

Time Frame Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 27 11
Mean (Standard Deviation)
Unit of Measure: days
0.0  (0.00) 0.0  (0.00)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments The threshold for statistical significance was p = 0.05.
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP)
Hide Description Intra-abdominal pressure values, which were routinely measured during ICU stay via urine bladder catheter.
Time Frame Days 1 - 6, D9 and D13 during Intensive Care Unit (ICU) stay
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The number of participants analyzed reflects the number of patients that were alive and had sufficient data to allow for calculation of the outcome measure.
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 19 9
Mean (Standard Deviation)
Unit of Measure: mmHg
Day 1 Number Analyzed 19 participants 9 participants
15.4  (12.37) 10.3  (4.80)
Day 2 Number Analyzed 19 participants 8 participants
12.2  (3.58) 12.1  (6.01)
Day 3 Number Analyzed 16 participants 6 participants
13.1  (4.62) 10.3  (5.35)
Day 4 Number Analyzed 12 participants 5 participants
11.4  (6.60) 8.6  (5.32)
Day 5 Number Analyzed 10 participants 4 participants
10.5  (3.14) 12.5  (5.45)
Day 6 Number Analyzed 8 participants 1 participants
11.4  (5.29) 15.0  (0)
Day 9 Number Analyzed 4 participants 0 participants
11.0  (5.48)
Day 13 Number Analyzed 6 participants 0 participants
10.8  (4.49)
7.Secondary Outcome
Title The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples
Hide Description 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.
Time Frame Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
At the Baseline Visit, 2 patients in the FP-1201-lyo treatment group and 1 patient in the placebo treatment group were not tested for anti-drug antibodies.
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 25 10
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline Number Analyzed 25 participants 10 participants
0
   0.0%
0
   0.0%
Day 30 Number Analyzed 19 participants 9 participants
0
   0.0%
0
   0.0%
8.Secondary Outcome
Title The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS).
Hide Description 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.
Time Frame Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment).
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 27 11
Measure Type: Count of Participants
Unit of Measure: Participants
No symptoms - 0
5
  18.5%
2
  18.2%
No significant disability - 1
5
  18.5%
5
  45.5%
Slight disability - 2
3
  11.1%
1
   9.1%
Moderate disability - 3
2
   7.4%
0
   0.0%
Moderately severe disability - 4
3
  11.1%
0
   0.0%
Severe disability - 5
2
   7.4%
1
   9.1%
Death - 6
7
  25.9%
2
  18.2%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3620
Comments The threshold for statistical significance was p = 0.05.
Method Mantel Haenszel
Comments Exact Mantel-Haenszel Chi-Square Test
9.Secondary Outcome
Title Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters
Hide Description Number of TEAEs from vital signs data, laboratory data, physical examinations and spontaneous reporting when conscious.
Time Frame Day 0 to Day 30
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Safety (FAS-S) consisted of all randomised patients receiving study treatment and comprised the analysis set on which the evaluation of safety is based.
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 29 11
Measure Type: Number
Unit of Measure: Events
Product-related TEAEs 17 1
Severe TEAEs 28 2
Serious TEAEs 26 5
TEAEs Leading to Study Product Discontinuation 7 1
TEAEs Leading to Death 7 1
10.Secondary Outcome
Title 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
Hide Description

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
Time Frame Day 30 or Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Efficacy (FAS-E). As the study was discontinued, analyses were performed on the available data gathered thus far.
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 27 11
Mean (Standard Deviation)
Unit of Measure: days
ICU free days at Day 30 Number Analyzed 27 participants 11 participants
16.8  (12.39) 21.9  (11.06)
Days in hospital at Day 90 Number Analyzed 20 participants 9 participants
18.1  (9.84) 13.8  (9.97)
Days in another facility at Day 90 Number Analyzed 15 participants 8 participants
11.8  (23.79) 7.0  (19.80)
Days on hemodialysis at Day 30 Number Analyzed 21 participants 9 participants
0.9  (4.15) 0.0  (0.00)
Days on hemodialysis at Day 90 Number Analyzed 20 participants 9 participants
0.6  (2.68) 0.0  (0.00)
Organ failure free days at Day 30 Number Analyzed 27 participants 11 participants
0.0  (0.00) 0.0  (0.00)
Ventilation free days at Day 30 Number Analyzed 27 participants 11 participants
20.6  (10.62) 25.1  (8.85)
11.Other Pre-specified Outcome
Title Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker
Hide Description Concentration of Myxovirus Resistant Protein A (MxA)
Time Frame Day 0 up to Day 13
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that were alive and had data to allow for calculation of the outcome measure.
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 27 11
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng/mL
Baseline Number Analyzed 27 participants 11 participants
3.5
(2.4 to 5.1)
6.0
(3.3 to 11.0)
Day 1 Number Analyzed 27 participants 11 participants
15.0
(10.2 to 22.1)
5.1
(2.8 to 9.3)
Day 2 Number Analyzed 27 participants 10 participants
19.8
(13.5 to 29.1)
3.8
(2.1 to 7.0)
Day 3 Number Analyzed 25 participants 10 participants
21.2
(14.3 to 31.4)
3.3
(1.8 to 6.2)
Day 4 Number Analyzed 23 participants 9 participants
36.4
(24.4 to 54.2)
4.1
(2.2 to 7.7)
Day 5 Number Analyzed 22 participants 9 participants
48.3
(32.3 to 72.3)
3.1
(1.6 to 5.8)
Day 6 Number Analyzed 23 participants 8 participants
50.4
(33.9 to 75.1)
3.6
(1.9 to 6.8)
Day 9 Number Analyzed 20 participants 6 participants
14.3
(9.5 to 21.5)
4.8
(2.4 to 9.7)
Day 13 Number Analyzed 17 participants 3 participants
3.9
(2.5 to 5.9)
8.7
(3.7 to 20.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments The lower limit of quantification (LLOQ) is equal 5 ng/ml. Values below the LLOQ were set to LLOQ/2 = 2.5 ng/ml. Values over the upper limit of quantitation (ULOQ) were set to 320 ng/ml.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments Day 2, Day 3, Day 4, Day 5, and Day 6.
Method ANOVA
Comments Repeated measures ANOVA
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments The lower limit of quantification (LLOQ) is equal 5 ng/ml. Values below the LLOQ were set to LLOQ/2 = 2.5 ng/ml. Values over the upper limit of quantitation (ULOQ) were set to 320 ng/ml.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.13
Comments Baseline visit
Method ANOVA
Comments Repeated measures ANOVA
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments The lower limit of quantification (LLOQ) is equal 5 ng/ml. Values below the LLOQ were set to LLOQ/2 = 2.5 ng/ml. Values over the upper limit of quantitation (ULOQ) were set to 320 ng/ml.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0035
Comments Day 1
Method ANOVA
Comments Repeated measures ANOVA
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments The lower limit of quantification (LLOQ) is equal 5 ng/ml. Values below the LLOQ were set to LLOQ/2 = 2.5 ng/ml. Values over the upper limit of quantitation (ULOQ) were set to 320 ng/ml.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments Day 9
Method ANOVA
Comments Repeated measures ANOVA
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments The lower limit of quantification (LLOQ) is equal 5 ng/ml. Values below the LLOQ were set to LLOQ/2 = 2.5 ng/ml. Values over the upper limit of quantitation (ULOQ) were set to 320 ng/ml.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments Day 13
Method ANOVA
Comments Repeated measures ANOVA
12.Other Pre-specified Outcome
Title Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples
Hide Description CD73 (ecto-5'-nucleotidase enzyme) concentration
Time Frame Day 0 up to Day 13
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that were alive and had data to allow for calculation of the outcome measure.
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 27 11
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng/mL
Baseline Number Analyzed 27 participants 11 participants
2.1
(1.8 to 2.5)
2.2
(1.7 to 2.9)
Day 1 Number Analyzed 27 participants 11 participants
2.0
(1.7 to 2.4)
2.2
(1.6 to 2.8)
Day 2 Number Analyzed 27 participants 9 participants
2.2
(1.8 to 2.6)
2.2
(1.7 to 3.0)
Day 3 Number Analyzed 25 participants 10 participants
2.0
(1.7 to 2.4)
2.3
(1.7 to 3.1)
Day 4 Number Analyzed 24 participants 9 participants
2.3
(1.9 to 2.8)
2.6
(1.9 to 3.5)
Day 5 Number Analyzed 23 participants 9 participants
3.0
(2.4 to 3.6)
3.5
(2.6 to 4.8)
Day 6 Number Analyzed 23 participants 8 participants
3.8
(3.2 to 4.6)
3.8
(2.7 to 5.2)
Day 9 Number Analyzed 20 participants 6 participants
3.9
(3.2 to 4.8)
3.8
(2.6 to 5.4)
Day 13 Number Analyzed 17 participants 3 participants
2.9
(2.3 to 3.6)
2.7
(1.7 to 4.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments Patients with an observation below the lower limit of quantification (LLOQ) value at baseline for CD73 were set to have the LLOQ value (LLOQ = 4 ng/ml) at baseline for subgroup determination purposes (2-fold increase in CD73 from baseline). Values below the LLOQ were set to LLOQ/2 = 2 ng/mL.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.66
Comments The threshold for statistical significance was p = 0.05.
Method ANOVA
Comments Repeated measures ANOVA
13.Other Pre-specified Outcome
Title Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples
Hide Description IL-6 concentration.
Time Frame Day 0 up to Day 13
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set for Efficacy (FAS-E) defined as all randomised patients who received study treatment, excluding the early deaths (within 36 hours from first dose of the study treatment). The overall number of participants analyzed reflects the number of patients that were alive and had data to allow for calculation of the outcome measure.
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 27 11
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mL
Baseline Number Analyzed 27 participants 11 participants
328.9
(223.8 to 483.3)
378.9
(207.3 to 692.6)
Day 1 Number Analyzed 27 participants 11 participants
493.1
(335.5 to 724.5)
460.2
(251.8 to 841.0)
Day 3 Number Analyzed 25 participants 10 participants
181.4
(122.0 to 270.0)
130.7
(69.8 to 244.8)
Day 6 Number Analyzed 22 participants 8 participants
164.1
(108.1 to 249.2)
79.1
(39.8 to 157.1)
Day 9 Number Analyzed 20 participants 6 participants
107.9
(69.9 to 166.5)
74.5
(34.4 to 161.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FP-1201-lyo 10 µg, FP-1201-lyo Placebo
Comments Observations of zero were imputed as 1 pg/ml before logarithmic transformation.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3
Comments The threshold for statistical significance was p = 0.05.
Method ANOVA
Comments Repeated measures ANOVA
14.Other Pre-specified Outcome
Title Tentative Disease Specific, Potential Inflammatory Marker - Hepatocyte Growth Factor [HGF]) in Serum Samples
Hide Description HGF concentration.
Time Frame Day 0 up to Day 13
Hide Outcome Measure Data
Hide Analysis Population Description
Data were not collected or analyzed due to the small groups and interference of corticosteroids it was not meaningful to perform the analyzes.
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description:

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame The Adverse Event (AE) reporting period was up to study D30. In accordance with the protocol, the investigators reported AEs occurring after D30 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until D90.
Adverse Event Reporting Description The "Serious Adverse Event" list and the "Other (Not including Serious) Adverse Event" list present all reported Treatment Emergent Adverse Events (defined as an AE that begins or that worsens in severity after at least one dose of study drug). In 3 study subjects a non-treatment emergent SAE began before first dose of the study drug (included in mortality numbers because these SAEs led to death)
 
Arm/Group Title FP-1201-lyo 10 µg FP-1201-lyo Placebo
Hide Arm/Group Description

FP-1201-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.

Interferon Beta-1a: investigational drug.

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

Placebo: placebo for investigational drug.

All-Cause Mortality
FP-1201-lyo 10 µg FP-1201-lyo Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   7/29 (24.14%)      2/11 (18.18%)    
Hide Serious Adverse Events
FP-1201-lyo 10 µg FP-1201-lyo Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/29 (44.83%)      3/11 (27.27%)    
Cardiac disorders     
Myocardial ischaemia  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Gastrointestinal disorders     
Gastric ulcer haemorrhage  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Gastrointestinal necrosis  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Intestinal ischaemia  1  3/29 (10.34%)  3 1/11 (9.09%)  1
Large intestine perforation  1  3/29 (10.34%)  3 0/11 (0.00%)  0
General disorders     
Condition aggravated  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Multiple organ dysfunction syndrome  1  4/29 (13.79%)  4 0/11 (0.00%)  0
Immune system disorders     
Anaphylactic reaction  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Infections and infestations     
Pneumonia  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Sepsis  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Septic shock  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Injury, poisoning and procedural complications     
Post procedural haemorrhage  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Pulmonary contusion  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Road traffic accident  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Sternal fracture  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Nervous system disorders     
Ischaemic cerebral infarction  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Paraplegia  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Spinal epidural haematoma  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Renal and urinary disorders     
Renal failure  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Pulmonary oedema  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Respiratory disorder  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Respiratory failure  1  1/29 (3.45%)  1 0/11 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
FP-1201-lyo 10 µg FP-1201-lyo Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/29 (93.10%)      9/11 (81.82%)    
Blood and lymphatic system disorders     
Anaemia  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Haemorrhagic anaemia  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Leukocytosis  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Thrombocytopenia  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Cardiac disorders     
Atrial fibrillation  1  5/29 (17.24%)  5 3/11 (27.27%)  4
Cardiac failure congestive  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Tachycardia  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Tachycardia paroxysmal  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Eye disorders     
Eye irritation  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Gastrointestinal disorders     
Constipation  1  3/29 (10.34%)  3 0/11 (0.00%)  0
Diarrhoea  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Ileus  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Nausea  1  2/29 (6.90%)  2 0/11 (0.00%)  0
General disorders     
Chills  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Pain  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Pyrexia  1  6/29 (20.69%)  6 1/11 (9.09%)  1
Systemic inflammatory response syndrome  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Hepatobiliary disorders     
Hepatic failure  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Infections and infestations     
Candida infection  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Catheter site infection  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Clostridium difficile colitis  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Device related infection  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Fungal skin infection  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Infection  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Influenza  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Lung infection  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Pneumonia  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Postoperative wound infection  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Pyelonephritis  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Urinary tract infection  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Injury, poisoning and procedural complications     
Abdominal wound dehiscence  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Anaemia postoperative  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Periprocedural myocardial infarction  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Post procedural constipation  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Post procedural haemorrhage  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Post procedural oedema  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Postoperative delirium  1  1/29 (3.45%)  1 1/11 (9.09%)  1
Procedural pain  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Wound dehiscence  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Wound secretion  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Investigations     
Alanine aminotransferase increased  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Aspartate aminotransferase increased  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Blood alkaline phosphatase increased  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Blood bilirubin increased  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Blood calcium decreased  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Blood creatine increased  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Blood potassium decreased  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Blood pressure increased  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Blood sodium increased  1  1/29 (3.45%)  1 0/11 (0.00%)  0
C-reactive protein increased  1  3/29 (10.34%)  3 1/11 (9.09%)  1
Haemoglobin decreased  1  4/29 (13.79%)  4 1/11 (9.09%)  1
Hepatic enzyme increased  1  3/29 (10.34%)  3 0/11 (0.00%)  0
Inflammatory marker increased  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Intra-abdominal pressure increased  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Liver function test abnormal  1  2/29 (6.90%)  2 1/11 (9.09%)  1
Neutrophil count increased  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Urine output decreased  1  2/29 (6.90%)  2 0/11 (0.00%)  0
White blood cell count increased  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Metabolism and nutrition disorders     
Hyperglycaemia  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Hypokalaemia  1  3/29 (10.34%)  3 1/11 (9.09%)  1
Musculoskeletal and connective tissue disorders     
Rhabdomyolysis  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Soft tissue necrosis  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Nervous system disorders     
Akathisia  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Psychiatric disorders     
Agitation  1  1/29 (3.45%)  1 1/11 (9.09%)  1
Anxiety  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Confusional state  1  4/29 (13.79%)  4 2/11 (18.18%)  2
Delirium  1  2/29 (6.90%)  2 1/11 (9.09%)  1
Disorientation  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Restlessness  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Sleep disorder  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Renal and urinary disorders     
Acute kidney injury  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Oliguria  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Renal failure  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Aspiration  1  2/29 (6.90%)  2 0/11 (0.00%)  0
Atelectasis  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Bronchospasm  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Emphysema  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Lung infiltration  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Obstructive airways disorder  1  0/29 (0.00%)  0 1/11 (9.09%)  1
Pleural effusion  1  2/29 (6.90%)  2 1/11 (9.09%)  1
Pulmonary embolism  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Respiratory failure  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Vascular disorders     
Embolism arterial  1  0/29 (0.00%)  0 1/11 (9.09%)  2
Hypertension  1  4/29 (13.79%)  4 2/11 (18.18%)  2
Hypotension  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Hypovolaemic shock  1  1/29 (3.45%)  1 0/11 (0.00%)  0
Peripheral ischaemia  1  0/29 (0.00%)  0 1/11 (9.09%)  1
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
The study was prematurely stopped and due to this the planned statistical power for the primary comparisons was not reached.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Faron Pharmaceuticals Ltd
Phone: +3584005529411
EMail: medical@faron.com
Layout table for additonal information
Responsible Party: Faron Pharmaceuticals Ltd
ClinicalTrials.gov Identifier: NCT03119701    
Other Study ID Numbers: FP1CLI006
2014-000899-25 ( EudraCT Number )
First Submitted: March 3, 2017
First Posted: April 19, 2017
Results First Submitted: September 22, 2020
Results First Posted: January 14, 2021
Last Update Posted: January 14, 2021