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

NCT04333420 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IFX-1-P2.92020-001335-28
• Study Type: interventional
• Target: 399
• Locations: 9 countries
• Sites: 48

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)

Conditions

Severe COVID-19 Pneumonia

Keywords

COVID-19 related severe pneumonia

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Phase II: All-cause 28-day Mortality (FAS)

  Day 28

• Phase II: Early Response at Day 7 After Enrollment

  Day 7

• Phase II: Late Response Until Day 28 After Enrollment

  Baseline until Day 28

• Phase II: Relative Change From Baseline in Oxygenation Index in Supine Position (FAS)

  Baseline, Day 3, Day 7, Day 9, Day 11, Day 15

• Phase III: 60-day All-cause Mortality (FAS)

  Day 60

Study Arms (4)

Phase II: IFX-1 + BSC

EXPERIMENTAL

Phase II study part: IFX-1: 800mg intravenously administered, BSC: Best supportive care

Drug: IFX-1 + BSC

Phase II: BSC

OTHER

Phase II study part: BSC: Best supportive care

Drug: BSC

Phase III: IFX-1 + SOC

EXPERIMENTAL

Phase III study part: IFX-1: 800mg intravenously administered, SOC: Standard of care

Drug: IFX-1 + SOC

Phase III: Placebo + SOC

PLACEBO COMPARATOR

Phase III study part: Placebo: placebo infusion intravenously administered, SOC: Standard of care

Drug: Placebo + SOC

Interventions

IFX-1 + BSC DRUG

Phase II study part: IFX-1 + BSC

Also known as: Vilobelimab + Best Supportive Care

Phase II: IFX-1 + BSC

BSC DRUG

Phase II study part: BSC

Also known as: Best Supportive Care

Phase II: BSC

IFX-1 + SOC DRUG

Phase III study part: IFX-1 + SOC

Also known as: Vilobelimab + Standard of Care

Phase III: IFX-1 + SOC

Placebo + SOC DRUG

Phase III study part: Placebo + SOC

Also known as: Placebo + Standard of Care

Phase III: Placebo + SOC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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:
• 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)
• 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.)

Sponsors & Collaborators

• InflaRx GmbH: lead

Study Sites (48)

InflaRx Site #1107

Aalst, Belgium

Location

InflaRx Site #1102

Brussels, Belgium

Location

InflaRx Site #1104

Leuven, Belgium

Location

InflaRx Site #1106

Lodelinsart, Belgium

Location

InflaRx Site #1101

Yvoir, Belgium

Location

InflaRx Site #0301

Belo Horizonte, Brazil

Location

InflaRx Site #0302

Campinas, Brazil

Location

InflaRx Site #0305

Criciúma, Brazil

Location

InflaRx Site #0308

Curitiba, Brazil

Location

InflaRx Site #0304

Porto Alegre, Brazil

Location

InflaRx Site #0303

São José, Brazil

Location

InflaRx Site #0306

São Paulo, Brazil

Location

InflaRx Site #1011

Grenoble, France

Location

InflaRx Site #1005

Nantes, France

Location

InflaRx Site #1009

Nantes, France

Location

InflaRx Site #1003

Nice, France

Location

InflaRx Site #1001

Paris, France

Location

InflaRx Site #1004

Paris, France

Location

InflaRx Site #1006

Paris, France

Location

InflaRx Site #1008

Paris, France

Location

InflaRx Site #1012

Saint-Etienne, France

Location

InflaRx Site #1002

Suresnes, France

Location

InflaRx Site #0201

Aachen, Germany

Location

InflaRx Site #0207

Augsburg, Germany

Location

InflaRx Site #0202

Berlin, Germany

Location

InflaRx Site #0208

Dresden, Germany

Location

InflaRx Site #0204

Essen, Germany

Location

InflaRx Site #0203

Greifswald, Germany

Location

InflaRx Site #0205

Hanover, Germany

Location

InflaRx Site #0206

Jena, Germany

Location

InflaRx Site #0502

Chihuahua City, Mexico

Location

InflaRx Site #0503

Culiacán, Mexico

Location

InflaRx Site #0506

Mérida, Mexico

Location

InflaRx Site #0504

Monterrey, Mexico

Location

InflaRx Site #0501

Nuevo León, Mexico

Location

InflaRx Site #0505

Veracruz, Mexico

Location

InflaRx Site #0101

Amsterdam, Netherlands

Location

InflaRx Site #0103

Amsterdam, Netherlands

Location

InflaRx Site #0106

Eindhoven, Netherlands

Location

InflaRx Site #0104

Enschede, Netherlands

Location

InflaRx Site #0102

Maastricht, Netherlands

Location

InflaRx Site #0601

Callao, Peru

Location

InflaRx Site #0603

Lima, Peru

Location

InflaRx Site #0604

Lima, Peru

Location

InflaRx Site #0701

Barnaul, Russia

Location

InflaRx Site #0704

Moscow, Russia

Location

InflaRx Site #0702

Ryazan, Russia

Location

InflaRx Site # 0804

Somerset West, South Africa

Location

Related Publications (6)

• van Amstel RBE, Slim MA, Lim EHT, Ruckinger S, Seymour CW, Burnett BP, Bos LDJ, van Vught LA, Riedemann NC, van de Beek D, Vlaar APJ; PANAMO Study Group. Heterogeneity of treatment effect of vilobelimab in COVID-19: a secondary analysis of a randomised controlled trial. Crit Care. 2024 Jun 28;28(1):210. doi: 10.1186/s13054-024-05004-z.

  PMID: 38943192 DERIVED

• Lim EHT, Vlaar APJ, de Bruin S, Ruckinger S, Thielert C, Habel M, Guo R, Burnett BP, Dickinson J, Brouwer MC, Riedemann NC, van de Beek D; PANAMO study group. Pharmacokinetic analysis of vilobelimab, anaphylatoxin C5a and antidrug antibodies in PANAMO: a phase 3 study in critically ill, invasively mechanically ventilated COVID-19 patients. Intensive Care Med Exp. 2023 Jun 19;11(1):37. doi: 10.1186/s40635-023-00520-8.

  PMID: 37332066 DERIVED

• 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.

  PMID: 36087611 DERIVED

• 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.

  PMID: 35029045 DERIVED

• 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.

  PMID: 34473343 DERIVED

• 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.

  PMID: 33015643 DERIVED

MeSH Terms

Interventions

vilobelimab; Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Prof. Niels C. Riedemann
• Organization: InflaRx GmbH

niels.Riedemann@inflarx.de

+49 3641-508-180

Study Officials

• A Vlaar, MD, PhD

  University Amsterdam

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Phase II: Open label study (30 patients), Phase III: Double- blind (360 patients)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Two phases with 2 parallel arms each

Study Record Dates

• First Submitted: April 1, 2020
• First Posted: April 3, 2020
• Study Start: March 31, 2020
• Primary Completion: October 31, 2021
• Study Completion: December 1, 2021
• Last Updated: June 5, 2023
• Results First Posted: June 5, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (5); PE (3); FR (10); BR (7); DE (8); NL (5); ZA (1); RU (3); ME (6)