NCT02622724: INTEREST

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

Terminated Phase 3 Results posted Last updated 30 March 2020

What this trial tests

Phase 3 trial testing Interferon beta-1a in Respiratory Distress Syndrome, Adult in 301 participants. Terminated before completion.

Timeline

23 December 2015

Primary endpoint
17 May 2018

23 May 2018

Quick facts

Lead sponsor	Faron Pharmaceuticals Ltd
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	301
Start date	23 December 2015
Primary completion	17 May 2018
Estimated completion	23 May 2018
Sites	71 locations across France, Italy, Finland, Belgium, United Kingdom, Germany, Spain, Czechia

Drugs / interventions tested

• Interferon beta-1a (INTERFERON BETA-1A) — full drug profile →
• Placebo

Conditions studied

• Respiratory Distress Syndrome, Adult — all drugs for Respiratory Distress Syndrome, Adult →

Sponsor

Faron Pharmaceuticals Ltd — full company profile →

Who can join

18 and older, any sex, with Respiratory Distress Syndrome, Adult. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Composite Endpoint (VFDsurv; All-cause Mortality and Number of Days Free of Mechanical Ventilation) at Day 28 Primary · 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 re

Group	Value	95% CI
FP-1201-lyo 10 μg	10	-1 – 26
Placebo	8.5	-1 – 26

Efficacy Endpoint: All-cause Mortality Secondary · At Day 28

Fatalities, mortality all-causes from randomisation up to Day 28

Group	Value	95% CI
FP-1201-lyo 10 μg	26.4	19 – 34
Placebo	23	17 – 31

Efficacy Endpoint: Mortality in ICU Secondary · Up to Day 28

All-cause mortality for subjects who died in Intensive Care Units up to Day 28.

Group	Value	95% CI
FP-1201-lyo 10 μg	25.7	19 – 34
Placebo	23.0	17 – 31

Efficacy Endpoint: Mortality in Hospital Secondary · 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.

Group	Value	95% CI
FP-1201-lyo 10 μg	1
Placebo	0

Other Secondary Efficacy Endpoints: Days Free of Organ Failure Secondary · 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.

Group	Value	95% CI
FP-1201-lyo 10 μg	0	0 – 28
Placebo	0	0 – 28

Other Secondary Efficacy Endpoints: Days Free of Renal Support Secondary · 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.

Group	Value	95% CI
FP-1201-lyo 10 μg	28	0 – 28
Placebo	27	0 – 28

Other Secondary Efficacy Endpoints: Days Free of Vasoactive Support Secondary · 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.

Group	Value	95% CI
FP-1201-lyo 10 μg	20	0 – 28
Placebo	21	1 – 28

Other Secondary Efficacy Endpoint: Days Free of Mechanical Ventilation Secondary · 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.

Group	Value	95% CI
FP-1201-lyo 10 μg	10	0 – 26
Placebo	9	0 – 26

Other Secondary Efficacy Endpoints: Number of ICU-free Days Secondary · 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.

Group	Value	95% CI
FP-1201-lyo 10 μg	6	0 – 24
Placebo	3.5	0 – 24

Other Secondary Efficacy Endpoints: Number of Days in Hospital Secondary · 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.

Group	Value	95% CI
FP-1201-lyo 10 μg	28	8 – 28
Placebo	28	8 – 28

Evaluation of Safety: Adverse Events and Deaths Secondary · 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

Subjects with TEAE

Group	Value	95% CI
FP-1201-lyo 10 μg	130
Placebo	132

Subjects with AE considered related to study drug

Group	Value	95% CI
FP-1201-lyo 10 μg	41
Placebo	33

Subjects with SAE

Group	Value	95% CI
FP-1201-lyo 10 μg	77
Placebo	77

Death

Group	Value	95% CI
FP-1201-lyo 10 μg	51
Placebo	53

Efficacy Endpoint: Presence of Neutralising Antibodies to IFN Beta-1a Secondary · 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.

Presence of BAbs to IFN β-1a at baseline

Group	Value	95% CI
FP-1201-lyo 10 μg	2
Placebo	2

Presence of BAbs to IFN β-1a at Day28

Group	Value	95% CI
FP-1201-lyo 10 μg	0
Placebo	1

Presence of NAbs to IFN β-1a at baseline

Group	Value	95% CI
FP-1201-lyo 10 μg	1
Placebo	0

Presence of NAbs to IFN β-1a at Day28

Group	Value	95% CI
FP-1201-lyo 10 μg	0
Placebo	0

Adverse events — posted to ClinicalTrials.gov

Time frame: The Adverse Event (AE) reporting period extended up to study Day 28. In accordance with the protocol, the investigators reported AEs occurring after Day 28 only if the investigator considered a causal relationship with the study drug. All deaths were reported as SAEs throughout the study, up until Day 360.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

FP-1201-lyo 10 μg

Serious: 77/144 (53%)

Deaths: 51/144

Placebo

Serious: 77/152 (51%)

Deaths: 53/152

Serious adverse events (126 terms)

Reaction	System	FP-1201-lyo 10 μg	Placebo
MULTI-ORGAN FAILURE	General disorders	—	—
CONDITION AGGRAVATED	General disorders	—	—
RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	—	—
PNEUMONIA	Infections and infestations	—	—
ACUTE RESPIRATORY DISTRESS SYNDROME	Respiratory, thoracic and mediastinal disorders	—	—
SEPTIC SHOCK	Infections and infestations	—	—
HYPOXIA	Respiratory, thoracic and mediastinal disorders	—	—
SHOCK HAEMORRHAGIC	Vascular disorders	—	—
CARDIAC ARREST	Cardiac disorders	—	—
ACUTE KIDNEY INJURY	Renal and urinary disorders	—	—
SEPSIS	Infections and infestations	—	—
SHOCK	Vascular disorders	—	—
HYPERTENSION	Vascular disorders	—	—
LARYNGEAL OEDEMA	Respiratory, thoracic and mediastinal disorders	—	—
PNEUMOTHORAX	Respiratory, thoracic and mediastinal disorders	—	—
DISEASE PROGRESSION	General disorders	—	—
CRITICAL ILLNESS POLYNEUROPATHY	Nervous system disorders	—	—
THROMBOCYTOPENIA	Blood and lymphatic system disorders	—	—
PNEUMOMEDIASTINUM	Respiratory, thoracic and mediastinal disorders	—	—
PULMONARY EMBOLISM	Respiratory, thoracic and mediastinal disorders	—	—
EMPYEMA	Infections and infestations	—	—
MYOCARDIAL INFARCTION	Cardiac disorders	—	—
INTESTINAL ISCHAEMIA	Gastrointestinal disorders	—	—
GASTROINTESTINAL HAEMORRHAGE	Gastrointestinal disorders	—	—
RENAL REPLACEMENT THERAPY	Surgical and medical procedures	—	—

Other adverse events (332 terms — click to expand)

Reaction	System	FP-1201-lyo 10 μg	Placebo
PYREXIA	General disorders	—	—
ANAEMIA	Blood and lymphatic system disorders	—	—
ATRIAL FIBRILLATION	Cardiac disorders	—	—
CONSTIPATION	Gastrointestinal disorders	—	—
HYPERTENSION	Vascular disorders	—	—
HYPERNATRAEMIA	Metabolism and nutrition disorders	—	—
HEPATOCELLULAR INJURY	Hepatobiliary disorders	—	—
PNEUMONIA	Infections and infestations	—	—
SEPSIS	Infections and infestations	—	—
PNEUMOTHORAX	Respiratory, thoracic and mediastinal disorders	—	—
PLEURAL EFFUSION	Respiratory, thoracic and mediastinal disorders	—	—
FLUID OVERLOAD	Metabolism and nutrition disorders	—	—
DELIRIUM	Psychiatric disorders	—	—
ACUTE KIDNEY INJURY	Renal and urinary disorders	—	—
DIARRHOEA	Gastrointestinal disorders	—	—
TRANSAMINASES INCREASED	Investigations	—	—
THROMBOCYTOPENIA	Blood and lymphatic system disorders	—	—
AGITATION	Psychiatric disorders	—	—
CRITICAL ILLNESS POLYNEUROPATHY	Nervous system disorders	—	—
TACHYCARDIA	Cardiac disorders	—	—
HYPOKALAEMIA	Metabolism and nutrition disorders	—	—
HYPOTENSION	Vascular disorders	—	—
RENAL FAILURE	Renal and urinary disorders	—	—
BACTERAEMIA	Infections and infestations	—	—
CONDITION AGGRAVATED	General disorders	—	—
VOMITING	Gastrointestinal disorders	—	—
BLOOD CREATINE PHOSPHOKINASE INCREASED	Investigations	—	—
THROMBOCYTOSIS	Blood and lymphatic system disorders	—	—
CHOLESTASIS	Hepatobiliary disorders	—	—
RHABDOMYOLYSIS	Musculoskeletal and connective tissue disorders	—	—
HYPOXIA	Respiratory, thoracic and mediastinal disorders	—	—
IMPAIRED GASTRIC EMPTYING	Gastrointestinal disorders	—	—
VENOUS THROMBOSIS	Vascular disorders	—	—
BLOOD ALKALINE PHOSPHATASE INCREASED	Investigations	—	—
HYPERBILIRUBINAEMIA	Hepatobiliary disorders	—	—
ANXIETY	Psychiatric disorders	—	—
SEPTIC SHOCK	Infections and infestations	—	—
DEVICE RELATED SEPSIS	Infections and infestations	—	—
URINARY TRACT INFECTION	Infections and infestations	—	—
RESPIRATORY FAILURE	Respiratory, thoracic and mediastinal disorders	—	—

Most-reported serious reactions: MULTI-ORGAN FAILURE, CONDITION AGGRAVATED, RESPIRATORY FAILURE, PNEUMONIA, ACUTE RESPIRATORY DISTRESS SYNDROME, SEPTIC SHOCK, HYPOXIA, SHOCK HAEMORRHAGIC.

Data from ClinicalTrials.gov NCT02622724 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Effect of Intravenous Interferon β-1a on Death and Days Free From Mechanical Ventilation Among Patients With Moderate to Severe Acute Respiratory Distress Syndrome: A Randomized Clinical Trial.
   Ranieri VM, Pettilä V, Karvonen MK, Jalkanen J, et al · · 2020 · cited 90× · PMID 32065831 · DOI 10.1001/jama.2019.22525
2. Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics.
   Pokharel MD, Garcia-Flores A, Marciano D, Franco MC, et al · · 2024 · cited 73× · PMID 38295575 · DOI 10.1016/j.redox.2024.103049
3. Harnessing Type I IFN Immunity Against SARS-CoV-2 with Early Administration of IFN-β.
   Vinh DC, Abel L, Bastard P, Cheng MP, et al · · 2021 · cited 40× · PMID 34101091 · DOI 10.1007/s10875-021-01068-6
4. Glucocorticoids inhibit type I IFN beta signaling and the upregulation of CD73 in human lung.
   Jalkanen J, Pettilä V, Huttunen T, Hollmén M, et al · · 2020 · cited 36× · PMID 32430515 · DOI 10.1007/s00134-020-06086-3
5. Acute Respiratory Distress Syndrome: Bench-to-Bedside Approaches to Improve Drug Development.
   Hussain M, Xu C, Ahmad M, Majeed A, et al · · 2018 · cited 24× · PMID 29484641 · DOI 10.1002/cpt.1034
6. Chemocentric Informatics Analysis: Dexamethasone <i>Versus</i> Combination Therapy for COVID-19.
   Hajjo R, Sabbah DA, Bardaweel SK. · · 2020 · cited 21× · PMID 33251412 · DOI 10.1021/acsomega.0c03597
7. What every intensivist should know about acute respiratory distress syndrome and diffuse alveolar damage.
   Rios F, Iscar T, Cardinal-Fernández P. · · 2017 · cited 17× · PMID 28977098 · DOI 10.5935/0103-507x.20170044
8. Polymorphism in interferon alpha/beta receptor contributes to glucocorticoid response and outcome of ARDS and COVID-19.
   Jalkanen J, Khan S, Elima K, Huttunen T, et al · · 2023 · cited 13× · PMID 36927455 · DOI 10.1186/s13054-023-04388-8