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

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)

Study Overview

• Status: Completed
• Conditions: Severe COVID-19 Pneumonia
• Intervention / Treatment: Drug: IFX-1 + BSC; Drug: BSC; Drug: IFX-1 + SOC; Drug: Placebo + SOC

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.

• Study Type: Interventional
• Enrollment (Actual): 399
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: InflaRx GmbH
• Investigators: Principal Investigator: A Vlaar, MD, PhD, University Amsterdam

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2020
• Primary Completion (Actual): October 31, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: April 1, 2020
• First Submitted That Met QC Criteria: April 1, 2020
• First Posted (Actual): April 3, 2020

Study Record Updates

• Last Update Posted (Actual): June 5, 2023
• Last Update Submitted That Met QC Criteria: May 25, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: COVID-19 related severe pneumonia
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Vilobelimab
• Other Study ID Numbers: IFX-1-P2.9; 2020-001335-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No