A phase II/III study of IFX-1 in patients with severe COVID-19 Pneumonia
- Conditions
- Severe pneumonia in context of COVID-19MedDRA version: 21.1Level: PTClassification code 10035737Term: Pneumonia viralSystem Organ Class: 10021881 - Infections and infestationsTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2020-001335-28-FR
- Lead Sponsor
- InflaRx GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 390
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 < 200 and > 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 290
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
Phase II
1. Oxygenation index at time of enrollment (PaO2 / FiO2) < 100 or > 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 < 6 months
17. Known to have received anti-cancer therapy for oncological disease in past 4 weeks
18. Known severe congestive heart failure (New York Heart Association [NYHA] Class III-IV; see Appendix 8)
Phase III
1. Intubated > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of Phase II was:<br>• To explore the effect of IFX-1 on COVID-19 related severe pneumonia (hypothesis generating)<br><br>The primary objective of Phase III is<br>• To demonstrate the efficacy of IFX-1 to improve survival outcomes of severe COVID-19 pneumonia (confirmative)<br>;Secondary Objective: The secondary objectives of Phase II and Phase III are:<br>• To assess and define other parameters of efficacy<br>• To assess the safety of IFX-1<br>;Primary end point(s): Phase II: <br>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.<br><br>Phase III: <br>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.<br><br>;Timepoint(s) of evaluation of this end point: Day 28
- Secondary Outcome Measures
Name Time Method