Randomized, Controlled Study of IFX-1 in Patients With Severe COVID-19 Pneumonia

Study Overview
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Brief Summary
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Phase II & Phase III: This is a pragmatic, adaptive, randomized, multicenter phase II/III study evaluating IFX-1 for the treatment of COVID-19 related severe pneumonia. The study consists of two parts: Phase II, an open-label, randomized, 2-arm phase evaluating best supportive care (BSC) + IFX-1 (Arm A) and BSC alone (Arm B); and Phase III, a double-blind, placebo-controlled, randomized phase comparing standard of care (SOC) + IFX-1 (Arm A) versus SOC + placebo-to-match (Arm B)

Detailed Description
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The phase II and Phase III portions enrolled patients subsequently. 1st patient was enrolled in the phase III portion on 1st October 2020.

Official Title
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A Pragmatic Adaptive Randomized, Controlled Phase II/III Multicenter Study of IFX-1 in Patients With Severe COVID-19 Pneumonia

Conditions
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Severe COVID-19 Pneumonia

Intervention / Treatment
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* Drug: IFX-1 + BSC
* Drug: BSC
* Drug: IFX-1 + SOC
* Drug: Placebo + SOC


Participation Criteria
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Eligibility Criteria
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Phase II Inclusion Criteria: At least 18 years of age or older Clinically evident or otherwise confirmed severe pneumonia SARS-CoV-2 infection confirmation (tested positive in last 14 days before randomization with locally available test system) Exclusion Criteria: Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months Patient moribund or expected to die in next 24h according to the judgment of the investigator Known severe congestive heart failure (New York Heart Association [NYHA] Class III- IV) Received organ or bone marrow transplantation in past 3 months Known cardio-pulmonary mechanical resuscitation in past 14 days Phase III: Inclusion Criteria: At least 18 years of age or older Patient on invasive mechanical ventilation (but not more than 48h post intubation at time point of first IMP administration) Patients with a PaO2 / FiO2 ratio of < 200 and > 60 at randomization (one representative measurement within 6h before randomization) SARS-CoV-2 infection confirmation (tested positive in last 14 days before randomization with locally available test system) Exclusion Criteria: Intubated > 48 h at time point of first IMP administration Expected stop of invasive ventilation or expected extubation in the next 24h without additional intervention according to judgment of the investigator 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 Known history of progressed COPD as evidenced by use of daily maintenance treatment with long-acting bronchodilators or inhaled/oral corticosteroids for > 2 months 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.) 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.) Received cytokine adsorption therapy in past 3 days Known severe congestive heart failure (corresponding to e.g. NYHA Class III-IV, left ventricular ejection fraction <40%) Known history of chronic liver disease (Child-Pugh B or C)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two phases with 2 parallel arms each
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase II: IFX-1 + BSC<br>Phase II study part: IFX-1: 800mg intravenously administered, BSC: Best supportive care | Drug: IFX-1 + BSC<br>* Phase II study part: IFX-1 + BSC<br>* Other names: Vilobelimab + Best Supportive Care;|
| Other: Phase II: BSC<br>Phase II study part: BSC: Best supportive care | Drug: BSC<br>* Phase II study part: BSC<br>* Other names: Best Supportive Care;|
| Experimental: Phase III: IFX-1 + SOC<br>Phase III study part: IFX-1: 800mg intravenously administered, SOC: Standard of care | Drug: IFX-1 + SOC<br>* Phase III study part: IFX-1 + SOC<br>* Other names: Vilobelimab + Standard of Care;|
| Placebo Comparator: Phase III: Placebo + SOC<br>Phase III study part: Placebo: placebo infusion intravenously administered, SOC: Standard of care | Drug: Placebo + SOC<br>* Phase III study part: Placebo + SOC<br>* Other names: Placebo + Standard of Care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position at Day 5 (FAS) | Relative change (%) from baseline in Oxygenation Index (OI; partial pressure of oxygen in the arterial blood (PaO2) / fractional inspired oxygen (FiO2)) in supine position for ≥2 hours at day 5 (FAS) | Baseline and Day 5 | 
| Phase III: 28-day All-cause Mortality (FAS) | Number and percentage of deaths (all-cause) until Day 28 (FAS) | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II: All-cause 28-day Mortality (FAS) | Number and percentage of deaths (all-cause) until Day 28 (FAS) | Day 28 | 
| Phase II: Early Response at Day 7 After Enrollment | Number of patients (%) achieving an early response at day 7 after enrollment (FAS) | Day 7 | 
| Phase II: Late Response Until Day 28 After Enrollment | Number of patients (%) reaching a late response until day 28 (FAS) | Baseline until Day 28 | 
| Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position (FAS) | Relative change (%) from baseline in Oxygenation Index (OI) in supine position for ≥2 hours at days 3, 7, 9, 11, and 15 (FAS) | Baseline, Day 3, Day 7, Day 9, Day 11, Day 15 | 
| Phase III: 60-day All-cause Mortality (FAS) | Number and percentage of deaths (all-cause) until Day 60 (FAS) | Day 60 | 
| Phase III: Percentage of Patients With an Improvement in the 8-point Ordinal Scale (FAS) | Percentage of patients with an improvement in the 8-point ordinal scale (Day 15, Day 28), the scale ranges from 0 = 'No clinical or virological evidence of infection' to 8 = 'Death' with higher scores meaning greater limitation and ventilation/organ support | Day 15, Day 28 | 
| Phase III: Percentage of Patients Developing Acute Kidney Failure Until Day 28 (FAS) | Percentage of patients developing acute kidney failure (estimated glomerular filtration rate [eGFR] < 15 mL/min/1.73m², assessed by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation requiring race information) until Day 28 (FAS) | Day 28 | 
| Phase III: Percentage of Patients Free of Any Renal Replacement Therapy Within 28 Days Upon Randomization (FAS) | Percentage of patients free of any renal replacement therapy (RRT) within 28 days upon randomization (FAS), number of patients free of any RRT = number of patients - number of patients with RRT initiated after randomization until Day 28 | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 related severe pneumonia