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

Severe COVID-19 Pneumonia Clinical Trial

— PANAMO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04333420
• Other study ID #: IFX-1-P2.9
• Secondary ID: 2020-001335-28
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: March 31, 2020
• Est. completion date: December 1, 2021

Study information

• Verified date: March 2023
• Source: InflaRx GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 399
• Est. completion date: December 1, 2021
• Est. primary completion date: October 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• COVID-19
• Pneumonia
• Severe COVID-19 Pneumonia

Intervention

Drug:
• IFX-1 + BSC
Phase II study part: IFX-1 + BSC
• BSC
Phase II study part: BSC
• IFX-1 + SOC
Phase III study part: IFX-1 + SOC
• Placebo + SOC
Phase III study part: Placebo + SOC

Locations

Country	Name	City	State
Belgium	InflaRx Site #1107	Aalst
Belgium	InflaRx Site #1102	Brussels
Belgium	InflaRx Site #1104	Leuven
Belgium	InflaRx Site #1106	Lodelinsart
Belgium	InflaRx Site #1101	Yvoir
Brazil	InflaRx Site #0301	Belo Horizonte
Brazil	InflaRx Site #0302	Campinas
Brazil	InflaRx Site #0305	Criciúma
Brazil	InflaRx Site #0308	Curitiba
Brazil	InflaRx Site #0304	Porto Alegre
Brazil	InflaRx Site #0303	São José
Brazil	InflaRx Site #0306	São Paulo
France	InflaRx Site #1011	Grenoble
France	InflaRx Site #1005	Nantes
France	InflaRx Site #1009	Nantes
France	InflaRx Site #1003	Nice
France	InflaRx Site #1001	Paris
France	InflaRx Site #1004	Paris
France	InflaRx Site #1006	Paris
France	InflaRx Site #1008	Paris
France	InflaRx Site #1012	Saint-Étienne
France	InflaRx Site #1002	Suresnes
Germany	InflaRx Site #0201	Aachen
Germany	InflaRx Site #0207	Augsburg
Germany	InflaRx Site #0202	Berlin
Germany	InflaRx Site #0208	Dresden
Germany	InflaRx Site #0204	Essen
Germany	InflaRx Site #0203	Greifswald
Germany	InflaRx Site #0205	Hannover
Germany	InflaRx Site #0206	Jena
Mexico	InflaRx Site #0502	Chihuahua
Mexico	InflaRx Site #0503	Culiacán
Mexico	InflaRx Site #0506	Mérida
Mexico	InflaRx Site #0504	Monterrey
Mexico	InflaRx Site #0501	Nuevo León
Mexico	InflaRx Site #0505	Veracruz
Netherlands	InflaRx Site #0101	Amsterdam
Netherlands	InflaRx Site #0103	Amsterdam
Netherlands	InflaRx Site #0106	Eindhoven
Netherlands	InflaRx Site #0104	Enschede
Netherlands	InflaRx Site #0102	Maastricht
Peru	InflaRx Site #0601	Callao
Peru	InflaRx Site #0603	Lima
Peru	InflaRx Site #0604	Lima
Russian Federation	InflaRx Site #0701	Barnaul
Russian Federation	InflaRx Site #0704	Moscow
Russian Federation	InflaRx Site #0702	Ryazan'
South Africa	InflaRx Site # 0804	Somerset West

Sponsors (1)

Lead Sponsor	Collaborator
InflaRx GmbH

Countries where clinical trial is conducted

Belgium,  Brazil,  France,  Germany,  Mexico,  Netherlands,  Peru,  Russian Federation,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Phase III: 28-day All-cause Mortality (FAS)	Number and percentage of deaths (all-cause) until Day 28 (FAS)	Day 28
Secondary	Phase II: All-cause 28-day Mortality (FAS)	Number and percentage of deaths (all-cause) until Day 28 (FAS)	Day 28
Secondary	Phase II: Early Response at Day 7 After Enrollment	Number of patients (%) achieving an early response at day 7 after enrollment (FAS)	Day 7
Secondary	Phase II: Late Response Until Day 28 After Enrollment	Number of patients (%) reaching a late response until day 28 (FAS)	Baseline until Day 28
Secondary	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
Secondary	Phase III: 60-day All-cause Mortality (FAS)	Number and percentage of deaths (all-cause) until Day 60 (FAS)	Day 60
Secondary	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
Secondary	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
Secondary	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