Multi Organ Failure, Preventive Medicine
Conditions
Keywords
Patients Surviving Open Surgery, 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.
Interventions
DRUGInterferon Beta-1A
Lyophilisate for solution for injection.
DRUGPlacebo
Lyophilisate for solution for injection as placebo.
Sponsors
Faron Pharmaceuticals Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality | Day 30 | Number of fatalities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples | 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). | 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 | 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 | 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 |
| The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality | Day 90 | Number of fatalities |
| The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs) | 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 | 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 Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | 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 | Day 0 up to Day 13 | CD73 (ecto-5'-nucleotidase enzyme) concentration |
| Tentative Disease Specific, Potential Inflammatory Marker - Hepatocyte Growth Factor [HGF]) in Serum Samples | Day 0 up to Day 13 | HGF concentration. |
| Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Day 0 up to Day 13 | IL-6 concentration. |
Countries
Estonia, Finland, Lithuania
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FP-1201-lyo 10 µg 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. | 27 |
| 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
Placebo: placebo for Investigational drug. | 11 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 6-day Dosing | Adverse Event | 3 | 0 |
| 6-day Dosing | Death | 4 | 1 |
| 6-day Dosing | Physician Decision | 0 | 1 |
| 6-day Dosing | Withdrawal by Subject | 0 | 1 |
| Mid-term (Final) Follow-up at D90 | Death | 3 | 1 |
Baseline characteristics
| Characteristic | FP-1201-lyo 10 µg | FP-1201-lyo Placebo | Total |
|---|---|---|---|
| Age, Customized 70-80 years | 14 Participants | 6 Participants | 20 Participants |
| Age, Customized < 70 years | 7 Participants | 3 Participants | 10 Participants |
| Age, Customized > 80 years | 6 Participants | 2 Participants | 8 Participants |
| Baseline Height | 172.3 centimetres STANDARD_DEVIATION 6.34 | 177.5 centimetres STANDARD_DEVIATION 7.59 | 173.8 centimetres STANDARD_DEVIATION 7.05 |
| Baseline Weight | 82.0 kilograms STANDARD_DEVIATION 16.14 | 95.9 kilograms STANDARD_DEVIATION 21.21 | 86.0 kilograms STANDARD_DEVIATION 18.58 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 27 Participants | 11 Participants | 38 Participants |
| Region of Enrollment Estonia | 1 participants | 2 participants | 3 participants |
| Region of Enrollment Finland | 23 participants | 8 participants | 31 participants |
| Region of Enrollment Lithuania | 3 participants | 1 participants | 4 participants |
| Sex: Female, Male Female | 4 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 23 Participants | 11 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 29 | 2 / 11 |
| other Total, other adverse events | 27 / 29 | 9 / 11 |
| serious Total, serious adverse events | 13 / 29 | 3 / 11 |
Outcome results
Primary
The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Number of fatalities
Time frame: Day 30
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality | 6 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality | 2 Participants |
p-value: 0.7895% CI: [0.21, 8.19]Regression, Logistic
Secondary
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
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
Population: The Full Analysis Set for Efficacy (FAS-E). As the study was discontinued, analyses were performed on the available data gathered thus far.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FP-1201-lyo 10 µg | 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 | ICU free days at Day 30 | 16.8 days | Standard Deviation 12.39 |
| FP-1201-lyo 10 µg | 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 | Days on hemodialysis at Day 30 | 0.9 days | Standard Deviation 4.15 |
| FP-1201-lyo 10 µg | 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 | Days in hospital at Day 90 | 18.1 days | Standard Deviation 9.84 |
| FP-1201-lyo 10 µg | 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 | Organ failure free days at Day 30 | 0.0 days | Standard Deviation 0 |
| FP-1201-lyo 10 µg | 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 | Days in another facility at Day 90 | 11.8 days | Standard Deviation 23.79 |
| FP-1201-lyo 10 µg | 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 | Ventilation free days at Day 30 | 20.6 days | Standard Deviation 10.62 |
| FP-1201-lyo 10 µg | 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 | Days on hemodialysis at Day 90 | 0.6 days | Standard Deviation 2.68 |
| FP-1201-lyo Placebo | 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 | Ventilation free days at Day 30 | 25.1 days | Standard Deviation 8.85 |
| FP-1201-lyo Placebo | 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 | Days on hemodialysis at Day 30 | 0.0 days | Standard Deviation 0 |
| FP-1201-lyo Placebo | 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 | Days on hemodialysis at Day 90 | 0.0 days | Standard Deviation 0 |
| FP-1201-lyo Placebo | 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 | Organ failure free days at Day 30 | 0.0 days | Standard Deviation 0 |
| FP-1201-lyo Placebo | 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 | ICU free days at Day 30 | 21.9 days | Standard Deviation 11.06 |
| FP-1201-lyo Placebo | 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 | Days in hospital at Day 90 | 13.8 days | Standard Deviation 9.97 |
| FP-1201-lyo Placebo | 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 | Days in another facility at Day 90 | 7.0 days | Standard Deviation 19.8 |
Secondary
Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters
Number of TEAEs from vital signs data, laboratory data, physical examinations and spontaneous reporting when conscious.
Time frame: Day 0 to Day 30
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FP-1201-lyo 10 µg | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters | Severe TEAEs | 28 Events |
| FP-1201-lyo 10 µg | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters | TEAEs Leading to Study Product Discontinuation | 7 Events |
| FP-1201-lyo 10 µg | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters | Serious TEAEs | 26 Events |
| FP-1201-lyo 10 µg | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters | TEAEs Leading to Death | 7 Events |
| FP-1201-lyo 10 µg | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters | Product-related TEAEs | 17 Events |
| FP-1201-lyo Placebo | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters | TEAEs Leading to Death | 1 Events |
| FP-1201-lyo Placebo | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters | Product-related TEAEs | 1 Events |
| FP-1201-lyo Placebo | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters | Severe TEAEs | 2 Events |
| FP-1201-lyo Placebo | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters | Serious TEAEs | 5 Events |
| FP-1201-lyo Placebo | Safety Parameters of Clinically Significant Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events, Vital Signs and Clinical Laboratory Parameters | TEAEs Leading to Study Product Discontinuation | 1 Events |
Secondary
The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality
Number of fatalities
Time frame: Day 90
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality | 7 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning All Cause Mortality | 2 Participants |
p-value: 0.5795% CI: [0.28, 10.52]Regression, Logistic
Secondary
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS).
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | Slight disability - 2 | 3 Participants |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | Moderately severe disability - 4 | 3 Participants |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | No significant disability - 1 | 5 Participants |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | Severe disability - 5 | 2 Participants |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | Moderate disability - 3 | 2 Participants |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | Death - 6 | 7 Participants |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | No symptoms - 0 | 5 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | Death - 6 | 2 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | No symptoms - 0 | 2 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | No significant disability - 1 | 5 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | Slight disability - 2 | 1 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | Moderate disability - 3 | 0 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | Moderately severe disability - 4 | 0 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Disability by Modified Ranking Scale (mRS). | Severe disability - 5 | 1 Participants |
p-value: 0.362Mantel Haenszel
Secondary
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples | Baseline | 0 Participants |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples | Day 30 | 0 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples | Baseline | 0 Participants |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Neutralizing Antibodies Against IFN Beta-1a (NAbs) in Whole Blood Samples | Day 30 | 0 Participants |
Secondary
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis
Number of days receiving hemodialysis. There were only few reported values other than zero.
Time frame: Day 30 and Day 90
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis | Day 30 | 0.9 days | Standard Deviation 4.15 |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis | Day 90 | 0.6 days | Standard Deviation 2.68 |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis | Day 30 | 0.0 days | Standard Deviation 0 |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Days Receiving Hemodialysis | Day 90 | 0.0 days | Standard Deviation 0 |
Secondary
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
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FP-1201-lyo 10 µg | 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 | 0.0 days | Standard Deviation 0 |
| FP-1201-lyo Placebo | 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 | 0.0 days | Standard Deviation 0 |
p-value: >0.999Wilcoxon (Mann-Whitney)
Secondary
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs)
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs) | 25.0 days |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Number of Ventilator Free Days (VFDs) | 29.0 days |
p-value: 0.08Wilcoxon (Mann-Whitney)
Secondary
The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP)
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 1 | 15.4 mmHg | Standard Deviation 12.37 |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 3 | 13.1 mmHg | Standard Deviation 4.62 |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 4 | 11.4 mmHg | Standard Deviation 6.6 |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 5 | 10.5 mmHg | Standard Deviation 3.14 |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 6 | 11.4 mmHg | Standard Deviation 5.29 |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 9 | 11.0 mmHg | Standard Deviation 5.48 |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 13 | 10.8 mmHg | Standard Deviation 4.49 |
| FP-1201-lyo 10 µg | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 2 | 12.2 mmHg | Standard Deviation 3.58 |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 1 | 10.3 mmHg | Standard Deviation 4.8 |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 4 | 8.6 mmHg | Standard Deviation 5.32 |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 2 | 12.1 mmHg | Standard Deviation 6.01 |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 6 | 15.0 mmHg | Standard Deviation 0 |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 3 | 10.3 mmHg | Standard Deviation 5.35 |
| FP-1201-lyo Placebo | The Efficacy of FP-1201-lyo Compared to Placebo Concerning Prevalence of Abdominal Compartment Syndrome by Intra-abdominal Pressure (IAP) | Day 5 | 12.5 mmHg | Standard Deviation 5.45 |
Other Pre-specified
Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker
Concentration of Myxovirus Resistant Protein A (MxA)
Time frame: Day 0 up to Day 13
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FP-1201-lyo 10 µg | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 1 | 15.0 ng/mL |
| FP-1201-lyo 10 µg | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 5 | 48.3 ng/mL |
| FP-1201-lyo 10 µg | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 3 | 21.2 ng/mL |
| FP-1201-lyo 10 µg | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 6 | 50.4 ng/mL |
| FP-1201-lyo 10 µg | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 2 | 19.8 ng/mL |
| FP-1201-lyo 10 µg | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 9 | 14.3 ng/mL |
| FP-1201-lyo 10 µg | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 4 | 36.4 ng/mL |
| FP-1201-lyo 10 µg | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 13 | 3.9 ng/mL |
| FP-1201-lyo 10 µg | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Baseline | 3.5 ng/mL |
| FP-1201-lyo Placebo | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 13 | 8.7 ng/mL |
| FP-1201-lyo Placebo | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Baseline | 6.0 ng/mL |
| FP-1201-lyo Placebo | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 1 | 5.1 ng/mL |
| FP-1201-lyo Placebo | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 2 | 3.8 ng/mL |
| FP-1201-lyo Placebo | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 3 | 3.3 ng/mL |
| FP-1201-lyo Placebo | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 4 | 4.1 ng/mL |
| FP-1201-lyo Placebo | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 5 | 3.1 ng/mL |
| FP-1201-lyo Placebo | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 6 | 3.6 ng/mL |
| FP-1201-lyo Placebo | Myxovirus Resistant Protein A (MxA) Concentration in Whole Blood Samples as Pharmacodynamic Marker | Day 9 | 4.8 ng/mL |
Comparison: 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.p-value: <0.0001ANOVA
Comparison: 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.p-value: 0.13ANOVA
Comparison: 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.p-value: 0.0035ANOVA
Comparison: 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.p-value: 0.009ANOVA
Comparison: 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.p-value: 0.1ANOVA
Other Pre-specified
Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples
CD73 (ecto-5'-nucleotidase enzyme) concentration
Time frame: Day 0 up to Day 13
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FP-1201-lyo 10 µg | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 1 | 2.0 ng/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 5 | 3.0 ng/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 3 | 2.0 ng/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 6 | 3.8 ng/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 2 | 2.2 ng/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 9 | 3.9 ng/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 4 | 2.3 ng/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 13 | 2.9 ng/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Baseline | 2.1 ng/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 13 | 2.7 ng/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Baseline | 2.2 ng/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 1 | 2.2 ng/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 2 | 2.2 ng/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 3 | 2.3 ng/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 4 | 2.6 ng/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 5 | 3.5 ng/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 6 | 3.8 ng/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific Marker Cluster of Differentiation 73 (CD73, Ecto-5'-Nucleotidase Enzyme) Concentration in Serum Samples | Day 9 | 3.8 ng/mL |
Comparison: 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.p-value: 0.66ANOVA
Other Pre-specified
Tentative Disease Specific, Potential Inflammatory Marker - Hepatocyte Growth Factor [HGF]) in Serum Samples
HGF concentration.
Time frame: Day 0 up to Day 13
Population: Data were not collected or analyzed due to the small groups and interference of corticosteroids it was not meaningful to perform the analyzes.
Other Pre-specified
Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples
IL-6 concentration.
Time frame: Day 0 up to Day 13
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FP-1201-lyo 10 µg | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Day 1 | 493.1 pg/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Day 6 | 164.1 pg/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Baseline | 328.9 pg/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Day 9 | 107.9 pg/mL |
| FP-1201-lyo 10 µg | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Day 3 | 181.4 pg/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Day 9 | 74.5 pg/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Baseline | 378.9 pg/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Day 1 | 460.2 pg/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Day 3 | 130.7 pg/mL |
| FP-1201-lyo Placebo | Tentative Disease Specific, Potential Inflammatory Marker - Interleukin 6 (IL-6) in Serum Samples | Day 6 | 79.1 pg/mL |
Comparison: Observations of zero were imputed as 1 pg/ml before logarithmic transformation.p-value: 0.3ANOVA