Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in Patients Having Acute Respiratory Distress Syndrome (ARDS) (INTEREST)

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: NCT02622724
Recruitment Status : Terminated (Day 90 results indicate IMP did not reduce mortality or ventilator free days)
First Posted : December 4, 2015
Results First Posted : March 30, 2020
Last Update Posted : March 30, 2020
Sponsor:
Collaborator:
Seventh Framework Programme
Information provided by (Responsible Party):
Faron Pharmaceuticals Ltd

Brief Summary:
In this study effectiveness and safety of a new drug FP-1201-lyo (recombinant human interferon beta-1a) is compared to placebo. Investigation is conducted with patients who have acute respiratory distress syndrome (ARDS). The new drug is expected to reduce the time which a patient need to be on the ventilator and improve patient's chances of survival. Currently there are no approved drugs for treating moderate or severe ARDS patients.

Condition or disease Intervention/treatment Phase
Respiratory Distress Syndrome, Adult Drug: Interferon beta-1a Drug: Placebo Phase 3

Detailed Description:

This is a Phase III clinical study to investigate the efficacy and safety of FP-1201-lyo (recombinant human interferon [IFN] beta-1a) compared to placebo in patients diagnosed with moderate or severe acute respiratory distress syndrome (ARDS). Primary objective is to demonstrate the efficacy of FP-1201-lyo in improving the clinical course and outcome based on survival and need for mechanical ventilation. Currently there are no approved drugs for treating moderate or severe ARDS patients.

FP-1201-lyo is a lyophilised powder form of recombinant human IFN beta-1a reconstituted in water for injection and is administered intravenously.

Recombinant human IFN beta-1a is an approved treatment for patients for other indication and its safety profile in such patients is well characterised.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 301 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III Double-blind, Randomised, Parallel-Group Comparison of the Efficacy and Safety of FP-1201-lyo (Recombinant Human IFN Beta-1a) and Placebo in the Treatment of Patients With Moderate or Severe Acute Respiratory Distress Syndrome
Actual Study Start Date : December 23, 2015
Actual Primary Completion Date : May 17, 2018
Actual Study Completion Date : May 23, 2018


Arm Intervention/treatment
Experimental: 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.

Drug: Interferon beta-1a
Investigational drug
Other Names:
  • FP-1201-lyo
  • Traumakine
  • ATC code L03AB07

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

Drug: Placebo
Placebo for investigational drug
Other Name: FP-1201-lyo Placebo




Primary Outcome Measures :
  1. Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28 [ Time Frame: Day 28 ]
    VFDsurv is a composite measure of all-cause mortality and the number of days free of mechanical ventilation (VFDsurv) within 28 days among survivors. Ventilator-free days (VFDs) correspond to those days when unassisted breathing (UAB) was possible for a complete calendar day. UAB was defined as: spontaneously breathing with face mask, nasal prong oxygen or room air, T-piece breathing, tracheostomy mask breathing, CPAP less than or equal to 5 cmH2O without pressure support or intermittent mandatory ventilation assistance, use of CPAP or BIPAP solely for sleep apnoea management. A patient was reported as ventilator-free after 2 consecutive calendar days of unassisted breathing (a VFD value of 0 is assigned to patients who die without initiating UAB or who require more than 28 days of mechanical ventilation. All patients who die before Day28 are assigned a VFDsurv value of -1).


Secondary Outcome Measures :
  1. Efficacy Endpoint: All-cause Mortality [ Time Frame: At Day 28 ]
    Fatalities, mortality all-causes from randomisation up to Day 28

  2. Efficacy Endpoint: Mortality in ICU [ Time Frame: Up to Day 28 ]
    All-cause mortality for subjects who died in Intensive Care Units up to Day 28.

  3. Efficacy Endpoint: Mortality in Hospital [ Time Frame: Up to Day 28 ]
    This is the number of subjects who died in hospital (i.e. outside of Intensive Care Units) up to Day 28.

  4. Other Secondary Efficacy Endpoints: Days Free of Organ Failure [ Time Frame: Day 28 or last day in intensive care unit [ICU] if patient has left the ICU earlier than Day 28 ]
    The total number of days free of organ failure by Sequential Organ Failure Assessment (SOFA) methodology. Overall, the median number of days free of organ failure was 0 days in both the treatment groups.

  5. Other Secondary Efficacy Endpoints: Days Free of Renal Support [ Time Frame: Day 28 ]
    Days without renal support (any renal support was documented). Overall, the median number of days free of renal support was 28 days in the active group and 27 days in the placebo group.

  6. Other Secondary Efficacy Endpoints: Days Free of Vasoactive Support [ Time Frame: Day 28 ]

    Days without vasoactive support. The vasoactive support included catecholamine and non-catecholamine vasopressors, inotropes and vasodilating agents.

    Overall, the median number of days free of vasoactive support was 20 days in the active group and 21 days in the placebo group.


  7. Other Secondary Efficacy Endpoint: Days Free of Mechanical Ventilation [ Time Frame: Day 28 ]
    The total number of days free of mechanical ventilation has been derived from the Patient Status report recorded on each day during the 28-day period. Patients who died during this period have been assigned a value of zero. This variable differs from the calculated "Ventilation Free Days (VFD) endpoint, which contribute to the VDFsurv primary efficacy endpoint as it require additional conditions of unassisted breathing (UAB) to be met.

  8. Other Secondary Efficacy Endpoints: Number of ICU-free Days [ Time Frame: Day 28 ]
    Number of Intensive Care Unit free days up to Day 28, i.e. the patient is no longer receiving care in ICU. Patients who die during this period have been assigned a value of zero for the number of ICU care free days.

  9. Other Secondary Efficacy Endpoints: Number of Days in Hospital [ Time Frame: Day 28 ]
    Hospitalisation days (including the stay at Intensive Care Units). Patients who died during this period have been assigned a value of 28 for the number of days in ICU or in hospital.

  10. Evaluation of Safety: Adverse Events and Deaths [ Time Frame: AEs up to Day 28, only related after Day 28 and deaths up to Day 360 ]
    Adverse events (AE) up to Day 28. Per protocol, AEs occurring after Day 28 if the investigator considered a causal relationship with the study drug as well as all deaths up to Day 360 were reported. Treatment-emergent AEs (TEAEs) were defined as AEs that begins or worsens in intensity after at least one dose of study drug has been administered. Serious AEs (SAEs) were defined as any untoward medical occurrence that at any dose resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was an important medical event.

  11. Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a [ Time Frame: Baseline and Day 28 (or last day in intensive care unit [ICU] or at withdrawal, if earlier) ]
    The immunological response to FP-1201-lyo was assessed by monitoring presence of anti-drug binding antibodies (BAbs) and neutralising antibodies (NAbs) to IFN beta-1a on pre-dose Day 1 and at Day 28, the last day in ICU or early termination (if earlier). The BAbs were determined first, and if present, the NAbs were also determined. Presence of BAbs and NAbs were summarised categorically, using positive/negative classification.

  12. Efficacy Endpoint: Evaluation of Pharmacodynamic (PD) Using Myxovirus Resistance Protein A (MxA) Biomarker [ Time Frame: From baseline to Day 14 ]
    Evaluation of MxA biomarker change from baseline to D14 between treatments arms over time.

  13. Long-term Efficacy Endpoint: Change in Quality of Life From Baseline to Day 180 [ Time Frame: Change from baseline to Day 180 ]
    Quality of Life was assessed through EQ-5D-3L (EuroQol 5-Dimensions 3-Levels questionnaire). An EQ Visual Analogue Scale (VAS) total score (ranging from 0-100) was measured (0= Worst imaginable health state, 100= Best imaginable health state). The EQ-5D-3L VAS scores are numerically summarised as change from pre-dose (Day 1) to long term follow-up (Day 180 visit).

  14. Long-term Efficacy Endpoints Relating to Respiratory Functioning (FEV1) [ Time Frame: Day 180 ]
    Measuring FEV1 (forced expiratory volume in 1 second) assessed pulmonary function (airway obstruction, bronchoconstriction or bronchodilation). FEV1 is the volume exhaled during the first second of a forced expiratory manoeuvre, starting from the level of total lung capacity.

  15. Long-term Efficacy Endpoints Relating to Neurological Functioning (6MWT) [ Time Frame: Day 180 ]
    The 6-minute walk test (6MWT) measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. According to the ERS/ATS technical standard to which the 6MWT was done, the walk test is done twice and the best result is used. It is an evaluation of the global and integrated responses of all systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood and neuromuscular units and muscle metabolism. The self-paced 6MWT assesses the sub- maximal level of functional capacity and will better reflect the functional exercise level for daily activities. ANOVA parameters estimates (LS Means and 90 % conf.interval) for the overall treatment difference was analysed.


Other Outcome Measures:
  1. Evaluation of Safety: Vital Signs - Heart Rate [ Time Frame: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]

    Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point.

    No statistical analyses were made for vital signs.


  2. Evaluation of Safety: Vital Signs - Body Temperature [ Time Frame: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]

    Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point.

    No statistical analyses were made for vital signs.


  3. Evaluation of Safety: Vital Signs - Blood Pressure [ Time Frame: From baseline to Last Observation Performed (Day 28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]

    Vital signs were measured supine pre-dose on Day 1 (baseline) and daily up to Day 28 while the patient was in the ICU. The results at baseline and at last observation performed (LOP) were summarized overall by treatment, variable and time point.

    No statistical analyses were made for vital signs.


  4. Evaluation of Safety: Physical Examination [ Time Frame: From baseline to Last Observation Performed (D28 or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Physical examination data (covering the major body systems; general appearance, head [ear, nose and throat], cardiovascular, eyes, respiratory, abdomen, urogenital, musculoskeletal, neurological, lymph nodes and skin) were categorized as "normal"; "abnormal, not clinically significant;" "abnormal, clinically significant" or "not done". Physical examinations were performed at Screening, then at the Last day in ICU and Day 28 (Out of ICU) or Early Termination, from which the last observation performed is derived. The changes from baseline to the last observations performed are categorized as "no change", "change clinically significant"; "change not clinically significant", "not done".

  5. Evaluation of Safety: Laboratory Results [ Time Frame: From baseline to Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Laboratory safety assessments of biochemistry, haematology and urinalysis were performed daily during the stay at ICU. Laboratory data were classified according to normal ranges as out of range (OOR; not clinically significant), OOR (clinically significant), or OOR (clinically significant and an AE). Laboratory test results were summarised by actual results by baseline and last observation period.

  6. Evaluation of Pharmacoeconomics: Days Free of Organ Failure [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

  7. Evaluation of Pharmacoeconomics: Days Free of Renal Support [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

  8. Evaluation of Pharmacoeconomics: Days Free of Vasoactive Support [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

  9. Evaluation of Pharmacoeconomics: Days Free of Mechanical Ventilation [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

  10. Evaluation of Pharmacoeconomics: Number of ICU-free Days [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

  11. Evaluation of Pharmacoeconomics: Number of Days in Hospital [ Time Frame: Day 28 (or last day in ICU if patient has left the ICU earlier than Day 28, or at withdrawal) ]
    Due to the study terminating early, costs items from hospitals were not collected and pharmacoeconomic analyses could not be done.

  12. Exploratory Variables Relating to Efficacy: Composite Endpoint (Mortality and Days Free of Mechanical Ventilation) at Day 90 [ Time Frame: Within 90 days ]
    Composite endpoint including mortality and days free of mechanical ventilation (VFDsurv) within 90 days among survivors. Ventilation Free Survival at Day 90 has been classified as Dead, Alive but on a ventilator and Alive and breathing unassisted

  13. Change in the Treatment-specific Exploratory Biomarker Cluster of Differentiation 73 (CD73) Concentration [ Time Frame: From baseline to Day 14 ]
    Evaluation of Cluster of differentiation 73 (CD73) change from baseline to D14 between treatments arms over time.

  14. Changes in Levels of Potential Inflammatory Markers (PIMs) [ Time Frame: From baseline to Day 14 ]
    Evaluation of potential inflammatory markers (PIMs) change from baseline to D14 between treatments arms over time. Potential biomarkers included IL-1ra, IL-6, FGF basic, IP-10 and TNF-α.

  15. Pharmacogenetic Analysis [ Time Frame: Anytime from baseline to Day 28 ]
    An optional genetic sample was analysed for subjects based on a separate consent. A carrier frequency was analysed for a C/T polymorphism (rs9984723) located in the 3'PRIME_UTR/intron region of IFNAR2-gene, which encodes the beta chain for the IFN-alpha/beta receptor and encompasses a regulatory motif for the glucocorticoid receptor. Biomarker responders were defined by a 3-fold elevation in MxA and a 2-fold in CD73 in comparison to baseline.

  16. Exploratory, Extended Long-term Follow-up: Overall Mortality at Day 360 [ Time Frame: Day 360 /termination of study ]
    Fatalities; as the study was terminated early, the assessment time point for mortality at Day 360 was not reached. Therefore only the overall mortality at study termination is presented.

  17. Extended Long-term Follow-up Exploratory Endpoint: Change in Quality of Life From Baseline to Day 360 [ Time Frame: Change from baseline to Day 360 ]
    Quality of Life was assessed through EQ-5D-3L (EuroQol 5-Dimensions 3-Levels questionnaire). An EQ Visual Analogue Scale (VAS) total score (ranging from 0-100) was measured (0= Worst imaginable health state, 100= Best imaginable health state). The EQ-5D-3L VAS scores are numerically summarised as change from pre-dose (Day 1) to extended long term follow-up (Day 360 visit).

  18. Neurological Functioning (6MWT) at Extended Long-term Follow-up [ Time Frame: Day 360 ]
    The 6-minute walk test (6MWT) measures the distance that a patient can quickly walk on a flat, hard surface in a period of 6 minutes. According to the ERS/ATS technical standard to which the 6MWT was done, the walk test is done twice and the best result is used. It is an evaluation of the global and integrated responses of all systems involved during exercise, including the pulmonary and cardiovascular systems, systemic circulation, peripheral circulation, blood and neuromuscular units and muscle metabolism. The self-paced 6MWT assesses the sub- maximal level of functional capacity and will better reflect the functional exercise level for daily activities. ANOVA parameters estimates (LS Means and 90 % confidence intervals) for the overall treatment difference was analysed.

  19. Extended Long-term Follow-up Endpoint: Respiratory Functioning (FEV1) at Day 360 [ Time Frame: Day 360 ]
    Measuring FEV1 (forced expiratory volume in 1 second) assessed pulmonary function (airway obstruction, bronchoconstriction or bronchodilation). FEV1 is the volume exhaled during the first second of a forced expiratory manoeuvre, starting from the level of total lung capacity.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

All patients must be intubated and mechanically ventilated to diagnose ARDS and be eligible for the study

  1. Patient has a diagnosis of moderate or severe ARDS according to the Berlin definition of ARDS:

    • Acute onset of respiratory failure within 1 week of a known clinical insult or new or worsening respiratory symptoms
    • Respiratory failure associated with known ARDS risk factors and not fully explained by either cardiac failure or fluid overload (an objective assessment of cardiac failure or fluid overload is needed if no risk factors for ARDS [moderate or severe ARDS] are present)
    • Radiological abnormalities on chest X-ray or on computerised tomography scan, i.e., bilateral opacities that are not fully explained by effusions, nodules, masses or lobar/lung collapse
    • Hypoxaemia:

      • Moderate ARDS: PaO2/FiO2 >100 mmHg (>13.3 kPa) to ≤200 mmHg (≤26.6 kPa) with positive end expiratory pressure (PEEP) ≥5 cmH2O
      • Severe ARDS: PaO2/FiO2 ≤100 mmHg (≤13.3 kPa) with positive end expiratory pressure [PEEP] ≥5 centimeter of water [cmH2O]
  2. The radiological and hypoxaemia criteria (1.3 and 1.4) must be met within the same 24-hour period. The time of onset of ARDS is when the last of the two specified ARDS criteria is met
  3. Administration of the first dose of study drug must be planned to take place within 48 hours of moderate or severe ARDS diagnosis
  4. Patient is intubated and mechanically ventilated
  5. A signed informed consent form from the patient or the patient's personal legal representative or a professional legal representative must be available
  6. Patient is aged ≥18 years

Exclusion Criteria:

  1. Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
  2. Patient is simultaneously taking part in another pharmacotherapy protocol
  3. Patient is not expected to survive for 24 hours
  4. Patient has an underlying clinical condition where, in the opinion of the Investigator, it would be extremely unlikely that the patient would come off ventilation, e.g., motor neurone disease, Duchenne muscular dystrophy or rapidly progressive interstitial pulmonary fibrosis
  5. Patient has severe chronic obstructive pulmonary disease requiring long-term home oxygen therapy or mechanical ventilation (non-invasive ventilation or via tracheotomy) except for continuous positive airway pressure (CPAP) or bi-level positive airway pressure used solely for sleep-disordered breathing
  6. Patient has congestive heart failure, defined as New York Heart Association class IV
  7. Patient has acute left ventricular failure
  8. Patient has liver failure (Child-Pugh grade C)
  9. Patient has received any prior interferon
  10. Patient has known hypersensitivity to natural or recombinant IFN beta or to any of the excipients
  11. Patient is receiving renal dialysis therapy for chronic renal failure
  12. Patient is receiving extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support
  13. Patient has had any form of mechanical ventilation (invasive or non-invasive, excluding CPAP alone) for longer than 48 hours prior to the diagnosis of ARDS. Non-invasive ventilation has to be continuously applied for at least 12 hours per day in these 48 hours
  14. Patient has burns to ≥15% of their total body surface area

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02622724


Locations
Show Show 71 study locations
Sponsors and Collaborators
Faron Pharmaceuticals Ltd
Seventh Framework Programme
Investigators
Layout table for investigator information
Study Director: Geoffrey Bellingan, MD University College London Hospitals, NHS, London, UK
Study Director: V Marco Ranieri, Prof. MD Universita La Sapeinza Policlinico Umberto I, Rome, Italy
  Study Documents (Full-Text)

Documents provided by Faron Pharmaceuticals Ltd:
Study Protocol  [PDF] August 29, 2017
Statistical Analysis Plan  [PDF] April 19, 2018


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Faron Pharmaceuticals Ltd
ClinicalTrials.gov Identifier: NCT02622724    
Other Study ID Numbers: FPCLI002
2014-005260-15 ( EudraCT Number )
First Posted: December 4, 2015    Key Record Dates
Results First Posted: March 30, 2020
Last Update Posted: March 30, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Faron Pharmaceuticals Ltd:
ARDS, human
Acute Respiratory Distress Syndrome
Respiratory Insufficiency
Additional relevant MeSH terms:
Layout table for MeSH terms
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Syndrome
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Interferons
Interferon-beta
Interferon beta-1a
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic