Clinical trial NCT04333420: Randomized, Controlled Study of IFX-1 in Patients With Severe COVID-19 Pneumonia
Official title: A Pragmatic Adaptive Randomized, Controlled Phase II/III Multicenter Study of IFX-1 in Patients With Severe COVID-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Severe COVID-19 Pneumonia
Keywords: COVID-19 related severe pneumonia
Lead sponsor: InflaRx GmbH
Sponsor class: INDUSTRY
First posted: 2020-04-03
Enrollment: 399
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two phases with 2 parallel arms each
Primary purpose: TREATMENT

Brief 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)

Detailed description: The phase II and Phase III portions enrolled patients subsequently.

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

Eligibility criteria: 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)

Primary outcomes:
measure: Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position at Day 5 (FAS)
timeFrame: Baseline and Day 5
measure: Phase III: 28-day All-cause Mortality (FAS)
timeFrame: Day 28
Secondary outcomes:
measure: Phase II: All-cause 28-day Mortality (FAS)
timeFrame: Day 28
measure: Phase II: Early Response at Day 7 After Enrollment
timeFrame: Day 7
measure: Phase II: Late Response Until Day 28 After Enrollment
timeFrame: Baseline until Day 28
measure: Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position (FAS)
timeFrame: Baseline, Day 3, Day 7, Day 9, Day 11, Day 15
measure: Phase III: 60-day All-cause Mortality (FAS)
timeFrame: Day 60
measure: Phase III: Percentage of Patients With an Improvement in the 8-point Ordinal Scale (FAS)
timeFrame: Day 15, Day 28
measure: Phase III: Percentage of Patients Developing Acute Kidney Failure Until Day 28 (FAS)
timeFrame: Day 28
measure: Phase III: Percentage of Patients Free of Any Renal Replacement Therapy Within 28 Days Upon Randomization (FAS)
timeFrame: Day 28
Other outcomes:
Locations:
city: Aalst
country: Belgium
facility: InflaRx Site #1107
city: Brussels
country: Belgium
facility: InflaRx Site #1102
city: Leuven
country: Belgium
facility: InflaRx Site #1104
city: Lodelinsart
country: Belgium
facility: InflaRx Site #1106
city: Yvoir
country: Belgium
facility: InflaRx Site #1101
city: Belo Horizonte
country: Brazil
facility: InflaRx Site #0301
city: Campinas
country: Brazil
facility: InflaRx Site #0302
city: Criciúma
country: Brazil
facility: InflaRx Site #0305
city: Curitiba
country: Brazil
facility: InflaRx Site #0308
city: Porto Alegre
country: Brazil
facility: InflaRx Site #0304
city: São José
country: Brazil
facility: InflaRx Site #0303
city: São Paulo
country: Brazil
facility: InflaRx Site #0306
city: Grenoble
country: France
facility: InflaRx Site #1011
city: Nantes
country: France
facility: InflaRx Site #1005
city: Nantes
country: France
facility: InflaRx Site #1009
city: Nice
country: France
facility: InflaRx Site #1003
city: Paris
country: France
facility: InflaRx Site #1001
city: Paris
country: France
facility: InflaRx Site #1004
city: Paris
country: France
facility: InflaRx Site #1006
city: Paris
country: France
facility: InflaRx Site #1008
city: Saint-Étienne
country: France
facility: InflaRx Site #1012
city: Suresnes
country: France
facility: InflaRx Site #1002
city: Aachen
country: Germany
facility: InflaRx Site #0201
city: Augsburg
country: Germany
facility: InflaRx Site #0207
city: Berlin
country: Germany
facility: InflaRx Site #0202
city: Dresden
country: Germany
facility: InflaRx Site #0208
city: Essen
country: Germany
facility: InflaRx Site #0204
city: Greifswald
country: Germany
facility: InflaRx Site #0203
city: Hannover
country: Germany
facility: InflaRx Site #0205
city: Jena
country: Germany
facility: InflaRx Site #0206
city: Chihuahua
country: Mexico
facility: InflaRx Site #0502
city: Culiacán
country: Mexico
facility: InflaRx Site #0503
city: Monterrey
country: Mexico
facility: InflaRx Site #0504
city: Mérida
country: Mexico
facility: InflaRx Site #0506
city: Nuevo León
country: Mexico
facility: InflaRx Site #0501
city: Veracruz
country: Mexico
facility: InflaRx Site #0505
city: Amsterdam
country: Netherlands
facility: InflaRx Site #0101
city: Amsterdam
country: Netherlands
facility: InflaRx Site #0103
city: Eindhoven
country: Netherlands
facility: InflaRx Site #0106
city: Enschede
country: Netherlands
facility: InflaRx Site #0104
city: Maastricht
country: Netherlands
facility: InflaRx Site #0102
city: Callao
country: Peru
facility: InflaRx Site #0601
city: Lima
country: Peru
facility: InflaRx Site #0603
city: Lima
country: Peru
facility: InflaRx Site #0604
city: Barnaul
country: Russian Federation
facility: InflaRx Site #0701
city: Moscow
country: Russian Federation
facility: InflaRx Site #0704
city: Ryazan'
country: Russian Federation
facility: InflaRx Site #0702
city: Somerset West
country: South Africa
facility: InflaRx Site # 0804
Study officials:
affiliation: University Amsterdam
name: A Vlaar, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vlaar APJ, Witzenrath M, van Paassen P, Heunks LMA, Mourvillier B, de Bruin S, Lim EHT, Brouwer MC, Tuinman PR, Saraiva JFK, Marx G, Lobo SM, Boldo R, Simon-Campos JA, Cornet AD, Grebenyuk A, Engelbrecht JM, Mukansi M, Jorens PG, Zerbib R, Ruckinger S, Pilz K, Guo R, van de Beek D, Riedemann NC; PANAMO study group. Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022 Dec;10(12):1137-1146. doi: 10.1016/S2213-2600(22)00297-1. Epub 2022 Sep 7.
citation: Vlaar APJ, Lim EHT, de Bruin S, Ruckinger S, Pilz K, Brouwer MC, Guo RF, Heunks LMA, Busch MH, van Paassen P, Riedemann NC, van de Beek D. The anti-C5a antibody vilobelimab efficiently inhibits C5a in patients with severe COVID-19. Clin Transl Sci. 2022 Apr;15(4):854-858. doi: 10.1111/cts.13213. Epub 2022 Jan 14.
citation: Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, Neidhardt M, Piechotta V, Salomon S, Valk SJ, Monsef I, Schmaderer C, Wood EM, So-Osman C, Roberts DJ, McQuilten Z, Estcourt LJ, Skoetz N. SARS-CoV-2-neutralising monoclonal antibodies for treatment of COVID-19. Cochrane Database Syst Rev. 2021 Sep 2;9(9):CD013825. doi: 10.1002/14651858.CD013825.pub2.
citation: Vlaar APJ, de Bruin S, Busch M, Timmermans SAMEG, van Zeggeren IE, Koning R, Ter Horst L, Bulle EB, van Baarle FEHP, van de Poll MCG, Kemper EM, van der Horst ICC, Schultz MJ, Horn J, Paulus F, Bos LD, Wiersinga WJ, Witzenrath M, Rueckinger S, Pilz K, Brouwer MC, Guo RF, Heunks L, van Paassen P, Riedemann NC, van de Beek D. Anti-C5a antibody IFX-1 (vilobelimab) treatment versus best supportive care for patients with severe COVID-19 (PANAMO): an exploratory, open-label, phase 2 randomised controlled trial. Lancet Rheumatol. 2020 Dec;2(12):e764-e773. doi: 10.1016/S2665-9913(20)30341-6. Epub 2020 Sep 28.