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

• ClinicalTrials.gov Identifier: NCT04333420
• Recruitment Status: Completed
• First Posted: April 3, 2020
• Last Update Posted: April 22, 2022
• Sponsor: InflaRx GmbH
• Information provided by (Responsible Party): InflaRx GmbH

Tracking Information

• First Submitted Date: April 1, 2020
• First Posted Date: April 3, 2020
• Last Update Posted Date: April 22, 2022
• Actual Study Start Date: March 31, 2020
• Actual Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 16, 2020)

Mortality [ Time Frame: Day 28 ]

28-day all-cause mortality

Original Primary Outcome Measures (submitted: April 1, 2020)

Change in PaO2/FiO2 [ Time Frame: Baseline to Day 5 ]

Relative change (%) from baseline in Oxygenation Index (PaO2 / FiO2) to day 5.

Current Secondary Outcome Measures (submitted: September 16, 2020)

• Treatment Emergent Adverse Events [ Time Frame: Day1 to Day 60 ]
  Frequency, severity, and relatedness to study drug of serious and non-serious TEAEs
• Safety Parameters [ Time Frame: Day 15, Day 28 ]
  Proportion of patients with an improvement in the 8-point ordinal scale

Original Secondary Outcome Measures (submitted: April 1, 2020)

Patients achieving early response [ Time Frame: Baseline to Day 7 ]

Number of patients (%) achieving an Early Response

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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 enrolls patients subsequently.

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

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Phase II: Open label study (30 patients) Phase III: Double- blind; (360 patients)

Primary Purpose: Treatment

• Condition: Severe COVID-19 Pneumonia

Intervention

• Drug: SOC + IFX-1
  SOC + IFX-1
• Drug: SOC + Placebo
  SOC + Placebo

Study Arms

• Experimental: Arm A: SOC + IFX-1
  Intervention: Drug: SOC + IFX-1
• Experimental: Arm B : SOC + Placebo
  Intervention: Drug: SOC + Placebo

Publications *

• 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.
• 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.
• 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, 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 6, 2022): 399
• Original Estimated Enrollment (submitted: April 1, 2020): 130
• Actual Study Completion Date: December 31, 2021
• Actual Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Brazil, France, Germany, Mexico, Netherlands, Peru, Russian Federation, South Africa

Administrative Information

• NCT Number: NCT04333420
• Other Study ID Numbers: IFX-1-P2.9; 2020-001335-28 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: InflaRx GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: InflaRx GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: A Vlaar, MD; University Amsterdam

• PRS Account: InflaRx GmbH
• Verification Date: October 2021