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

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

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)

The phase II and Phase III portions enrolled patients subsequently.

1st patient was enrolled in the phase III portion on 1st October 2020.

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)