Severe pneumonia in context of COVID-19 MedDRA version: 21.1 Level: PT Classification code 10035737 Term: Pneumonia viral System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: IFX-1
Product Code: vilobelimab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IFX-1
CAS Number: 2250440-41-4
Current Sponsor code: IFX-1
Other descripti
Sponsors
InflaRx GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Phase II 1. At least 18 years of age or older 2. Clinically evident or otherwise confirmed severe pneumonia as evidenced by at least one of the following criteria: 3. Chest X-ray or computed tomography (CT) scan or magnetic resonance imaging (MRI) with pulmonary infiltrates consistent with pneumonia 4. Clinical history in past 14 days of newly developed severe shortness of breath (> 29 breaths / minute) in the absence of oxygen supply or spontaneous peripheral oxygenation = 92 with need for oxygen supply, or need for non-invasive or invasive ventilation (in conjunction with a positive test for SARS-CoV-2 infection) 5. Oxygenation index at time of enrollment (PaO2 / FiO2) = 250 and = 100 in supine position 6. SARS-CoV-2 infection confirmation (tested positive in last 14 days or test results to be obtained within 24h after enrollment, both with locally available test system). 7. No use OR stop of any corticosteroid treatment at time point of enrollment (topical treatment and systemic dose of = 10mg prednisone / day equivalent allowed) Phase III 1. At least 18 years of age or older 2. Patient on invasive mechanical ventilation (but not more than 48h post intubation at time point of first IMP randomization) 3. Patients with a PaO2 / FiO2 ratio of 60 at randomization (one representative measurement within 6h before randomization) 4. SARS-CoV-2 infection confirmation (tested positive in last 14 days before randomization with locally available test system) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 320 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
Exclusion criteria: Phase II 1. Oxygenation index at time of enrollment (PaO2 / FiO2) 250 in supine position 2. Intubated > 48h at time point of enrollment 3. Patients who demonstrate an improvement in past 24h prior to enrollment in oxygenation and ventilation / support parameters which indicate an expected resolution of lung dysfunction in the next 24h without additional intervention according to judgment of the investigator with one or more of the following parameters present: 4. Improvement in oxygenation index of > 30% relative to previous measure (last 24h in supine position) 5. Extubation if intubated before 6. Known history of chronic obstructive pulmonary disease (COPD) (GOLD category C or D) 7. Known history of chronic dialysis OR received renal replacement therapy in past 14 days 8. Received new other biologic treatment attempt for COVID-19 in the past 14 days 9. Received treatment with a viral replication inhibitor in past 3 days 10. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 11. Known pregnancy 12. Received organ or bone marrow transplantation in past 3 months 13. Known mechanically resuscitation in past 14 days 14. Patient moribund or expected to die in next 12h according to the judgment of the investigator 15. Patients otherwise considered restricted from receiving full supportive care (including ICU support) 16. Existing diagnosis of progressed cancer or other life-limiting disease with life expectancy 48h at time point of first IMP randomization 2. Expected stop of invasive ventilation or expected extubation in the next 24h without additional intervention according to judgment of the investigator 3. Known history of chronic dialysis OR received renal replacement therapy in past 14 days OR anticipated to receive renal replacement therapy within 24h after randomization 4. Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months 5. Treatment of COVID-19 with investigational antibody treatment(s) which are not approved or not included in locally adopted treatment guidelines (e.g., WHO guidance, National Institutes of Health [NIH] COVID-19 treatment guidelines) for this indication in the past 7 days (Note: Antibody treatment[s] given within past 7 days for pre-existing diseases, other than COVID-19, are allowed.) 6. At time point of randomization, treatment of COVID-19 with investigational treatments which are not approved or not included in locally adopted treatment guidelines for this indication (e.g., WHO guidance, NIH COVID-19 treatment guidelines), including SARS-CoV-2 multiplication inhibitor(s) or immunomodulator(s). (Note: If a locally adopted treatment guideline recommends drugs such as remdesivir, dexamethasone, or anticoagulation, this would be allowed. Adopted guidelines and updates must be documented at study initiation and throughout the conduct of the study.) 7. Received cytokine adsorption therapy in past 3 days 8. Known hypersensitivity to IFX-1 or any other ingredient of the study medication 9. Serum or urine pregnancy test positive before randomization (required for women of childbearing potential) 10. Received organ
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of Phase II was: • To explore the effect of IFX-1 on COVID-19 related severe pneumonia (hypothesis generating) The primary objective of Phase III is • To demonstrate the efficacy of IFX-1 to improve survival outcomes of severe COVID-19 pneumonia (confirmative) ;Secondary Objective: The secondary objectives of Phase II and Phase III are: • To assess and define other parameters of efficacy • To assess the safety of IFX-1 ;Primary end point(s): Phase II: The primary endpoint in Phase II was the relative change (%) from baseline (day 1 prior to study drug administration at ± 1h of randomization) in Oxygenation Index (PaO2 / FiO2) in supine position at day 5. Phase III: Based on the preliminary interim analysis of efficacy data from Phase II, the primary endpoint chosen for Phase III is 28-day all-cause mortality. ;Timepoint(s) of evaluation of this end point: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase II: • Number of patients (%) achieving an Early Response as defined as meeting ALL of the following criteria at day 7 after enrollment: ? Patient alive and extubated OR oxygenation index = 300 OR improvement of = 30% from baseline ? Temperature < 38°C in absence of fever decreasing medication of at least 4h ? White blood cell count within normal limit of local lab quantifications • Number of patients (%) reaching a Late Response as defined by either being discharged alive from hospital until day 28 OR meeting ALL of the following criteria at day 28 of the trial ? Patient alive and extubated ? Patient discharged from intensive care unit (ICU) ? Patient free of shortness of breath (respiratory rate [RR] < 20) in absence of oxygen supply ? Patient free of fever (< 37.6°C) • Relative change (%) from baseline (day 1 prior to study drug administration at ± 1h of randomization) in oxygenation index (PaO2 / FiO2) in supine position at day 3, 7, 9, and 11. • All cause 28-day mortality (%) • Frequency, severity, and relatedness to study drug of treatment-emergent adverse events (TEAEs) and SAEs Phase III: • 60-day all-cause mortality (proportion of patients deceased until Day 60) •Proportion of patients free of any renal replacement therapy within 28 days upon randomization • Proportion of patients developing acute kidney failure (eGFR < 15 mL/min/1.73m², assessed by the CKD-EPI equation requiring race information) during ICU stay and at day 28 • Proportion of patients with an improvement in the 8-point ordinal scale (Appendix 7) (day 15, day 28) • Frequency, severity, and relatedness to study drug of serious and non-serious TEAEs;Timepoint(s) of evaluation of this end point: During the conduct of the study until Day 60 | — |
Countries
Belgium, Brazil, France, Germany, Mexico, Netherlands, Peru, Russian Federation, South Africa, United States
Contacts
Public ContactClinical Research and Development
InflaRX GmbH
Outcome results
None listed