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

Trial Profile

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

Status: Recruiting
Phase of Trial: Phase II/III

Latest Information Update: 04 Nov 2020

At a glance

  • Drugs Vilobelimab (Primary)
  • Indications COVID-19 pneumonia
  • Focus Registrational; Therapeutic Use
  • Acronyms PANAMO
  • Sponsors InflaRx
  • Most Recent Events

    • 29 Oct 2020 According to an InflaRx media release, data from the Phase II part of the study were published in the peer-reviewed journal, The Lancet Rheumatology.
    • 16 Sep 2020 Planned End Date changed from 31 Dec 2020 to 31 Aug 2021.
    • 16 Sep 2020 Planned primary completion date changed from 31 Oct 2020 to 31 May 2021.

Trial Overview

Purpose

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)

Comments

According to an InflaRx media release, phase III part of this study is subject to regulatory approval.

Primary Endpoints

Change in PaO2/FiO2

description: Relative change (%) from baseline in Oxygenation Index (PaO2 / FiO2) to day 5.
time_frame: Baseline to Day 5

Phase II:
The primary endpoint in Phase II was the relative change (%) from baseline (day 1 prior to study drug administration at ± 1h of randomization) in Oxygenation Index (PaO2 / FiO2) in supine position at day 5.
Phase III:
Based on the preliminary interim analysis of efficacy data from Phase II, the primary endpoint chosen for Phase III is 28-day all-cause mortality.
Timepoint: Day 28

Mortality

description: 28-day all-cause mortality
time_frame: Day 28

Other Endpoints

Treatment Emergent Adverse Events

description: Frequency, severity, and relatedness to study drug of serious and non-serious TEAEs
time_frame: Day1 to Day 60

Safety Parameters

description: Proportion of patients with an improvement in the 8-point ordinal scale
time_frame: Day 15, Day 28 [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID-19 pneumonia treatment severe

Subjects

  • Subject Type patients
  • Number

    Planned: 390

  • Sex male & female
  • Age Group ≥ 18 years; adult; elderly

Patient 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)

Patient 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

Trial Details

Identifiers

Identifier Owner
NCT04333420 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001335-28 European Clinical Trials Database
IFX1P2-9 -

Organisations

  • Sponsors InflaRx
  • Affiliations InflaRx

Trial Dates

  • Initiation Dates

    Actual : 31 Mar 2020

  • Primary Completion Dates

    Planned : 31 May 2021

  • End Dates

    Planned : 31 Aug 2021

Other Details

  • Design double-blind; multicentre; open; parallel; prospective; randomised
  • Phase of Trial Phase II/III
  • Location Brazil; Europe; Germany; India; Mexico; Netherlands; Peru; Russia; South Africa; South America; USA
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
VilobelimabPrimary Drug Intravenous Infusion

Arm A: SOC + IFX-1

Drug: SOC + IFX-1 (SOC + IFX-1)

Arm B : SOC + Placebo

Drug: SOC + Placebo (SOC + Placebo)

Results

Therapeutic efficacy

In a part II of a phase II/III trials, being conducted in patients with severely progressed pneumonia associated with COVID-2019 infections, twenty-eight-day all-cause mortality in the vilobelimab treatment group was 13% (2 out of 15) versus 27% (4 out of 15) in the control group. In a vilobelimab treatment group, a higher number of patients with 2 or more comorbidities associated with increased COVID-19 mortality were reported, compared to best supportive care group. In the vilobelimab treatment group fewer patients experienced renal impairment assessed by estimated glomerular filtration rates and more patients showed reversal of blood lymphocytopenia and a greater lowering of lactate dehydrogenase concentrations as a sign of reduction in tissue damage. A temporary, but statistically significant increase of D-dimer levels in the first days following vilobelimab administration was reported, as a potential signal for induction of blood clot lysis. No statistically significant group differences on the relative percentage change from baseline to day five in oxygenation index (defined as PaO2/FiO2 ratio) were detected [2] [3] .

Adverse events

In a part II of a phase II/III trials, being conducted in patients with severely progressed pneumonia associated with COVID-2019 infections, vilobelimab treatment was well tolerated. There was one death in vilobelimab treatment arm after acute ventilator tube complication (leakage), the other death was due to pulmonary failure in patient with history of severe COPD. In the best supportive care group, there were four deaths due to COVID-2019 induced multi-organ failure. Three of these four were due to pulmonary embolisms as an SAE. Adverse events were comparatively lower in vilobelimab group [3] .

Publications

  1. InflaRx. InflaRx Reports Encouraging Topline Results from the Exploratory Phase II Part of the Adaptive Randomized Phase II/III Trial of IFX-1 in COVID-19. Media-Rel 2020;.

    Media Release

Authors

Author Total Publications First Author Last Author
InflaRx 1 1 1

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
A Vlaar, MD University Amsterdam Netherlands
Alexander Vlaar, MD, PhD University Amsterdam Netherlands
Clinical Research and Development
Winzerlaer Strasse 2
Jena
Postcode: 07745
Germany
Telephone: +4989414 1897897
korinna.pilz@inflarx.de
show details
InflaRX GmbH Germany
Korinna Pilz, MD
+49 89 4141 89 78 Ext: 0
korinna.pilz@inflarx.de
show details
, InflaRx GmbH
-
L.M.A Heunks, MD, PhD University Amsterdam Netherlands
Pieter van Paassen, MD University Maastricht Netherlands

Centres

Centre Name Location Trial Centre Country
-
-
-
InflaRx GmbH
-
-
InflaRX GmbH Jena Germany
University Amsterdam Amsterdam Netherlands
University Maastricht Maastricht Netherlands

Trial History

Event Date Event Type Comment
04 Nov 2020 Other trial event Last checked against the ClinicalTrials.gov record. Updated 04 Nov 2020
29 Oct 2020 Results According to an InflaRx media release, data from the Phase II part of the study were published in the peer-reviewed journal, The Lancet Rheumatology. Updated 03 Nov 2020
05 Oct 2020 Other trial event Last checked against European Clinical Trials Database record. Updated 05 Oct 2020
16 Sep 2020 Completion date Planned End Date changed from 31 Dec 2020 to 31 Aug 2021. Updated 21 Sep 2020
16 Sep 2020 Other trial event Planned primary completion date changed from 31 Oct 2020 to 31 May 2021. Updated 21 Sep 2020
14 Sep 2020 Other trial event According to an InflaRx media release, Additional sites to be added in the US, EU and other regions Updated 17 Sep 2020
14 Sep 2020 Other trial event According to an InflaRx media release, the phase II results have been accepted for publication in the peer-reviewed journal, The Lancet Rheumatology. Updated 15 Sep 2020
14 Sep 2020 Other trial event According to an InflaRx media release, the company announced today the start of the global Phase III part of this Phase II/III trial with the initiation of the first clinical site in the Netherlands. And, German regulatory authority, the Paul-Ehrlich-Institut (PEI), has approved the Phase III clinical trial in Germany Updated 15 Sep 2020
04 Sep 2020 Other trial event Planned number of patients changed from 130 to 390. Updated 04 Sep 2020
21 Jul 2020 Other trial event According to an InflaRx media release, phase III part of this study is subject to regulatory approval. Updated 23 Jul 2020
21 Jul 2020 Other trial event According to an InflaRx media release, other planned key endpoints for phase III part are assessments of organ support and assessment of disease improvement on the ordinal scale. Updated 23 Jul 2020
21 Jul 2020 Other trial event According to an InflaRx media release, the Company plans to enroll approximately 360 early intubated, critically ill patients with COVID-19 induced pneumonia in phase III part. The company plans to conduct the study at sites in the US, Europe, South America and potentially other regions and an interim analysis is currently planned after enrollment of 180 patients, with the potential for an early stop for efficacy or futility. Updated 23 Jul 2020
21 Jul 2020 Other trial event According to an InflaRx media release, the phase II results have been submitted for publication to a peer-reviewed medical journal along with a preprint server. Updated 23 Jul 2020
21 Jul 2020 Other trial event According to an InflaRx media release, the company will initiate the phase III part in the coming months. Updated 23 Jul 2020
17 Jun 2020 Other trial event According to an InflaRx media release, upon review of the safety data, the independent data safety monitoring board recommended continuation of the trial into the Phase III part. Updated 19 Jun 2020
17 Jun 2020 Other trial event According to an InflaRx media release, data are being prepared for submission to a scientific journal. Updated 19 Jun 2020
17 Jun 2020 Interim results Interim results (n=30) presented in an InflaRx Media Release. Updated 19 Jun 2020
29 Apr 2020 Other trial event According to an InflaRx media release, after all patients have been treated in the first part of the trial, an interim analysis will be performed to assess the clinical benefit of the treatment using the assessed clinical parameters in order to potentially adapt the confirmatory second part of the study. Part 1 is fully enrolled with 30 patients as of April 24, 2020. Additional centers have been opened in the Netherlands, since March 2020. Updated 04 May 2020
08 Apr 2020 Other trial event New source identified and integrated (European Clinical Trials Database; EudraCT2020-001335-28) Updated 08 Apr 2020
07 Apr 2020 New trial record New trial record Updated 07 Apr 2020
31 Mar 2020 Other trial event According to an InflaRx media release, InflaRx has dosed the first patient this study. Updated 07 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. InflaRx. InflaRx Announces Decision to Enter Phase III Development of IFX-1 in Severe COVID-19 Induced Pneumonia. Media-Rel 2020;.

    Media Release
  3. InflaRx. InflaRx Reports Encouraging Topline Results from the Exploratory Phase II Part of the Adaptive Randomized Phase II/III Trial of IFX-1 in COVID-19. Media-Rel 2020;.

    Media Release
  4. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  5. InflaRx. InflaRx Announces Initiation of Phase III Part of Phase II/III Clinical Trial with IFX-1 in Severe COVID-19 Induced Pneumonia. Media-Rel 2020;.

    Media Release
  6. InflaRx. InflaRx Doses First Patient in Multicenter Randomized Clinical Trial in Severe Progressed COVID-19 Pneumonia in Europe upon Receipt of Initial Positive Human Data with InflaRxs anti-C5a Technology. Media-Rel 2020;.

    Media Release
  7. InflaRx. InflaRx Reports Full Year 2019 Financial & Operating Results. Media-Rel 2020;.

    Media Release
  8. InflaRx. 09-2020-InflaRx Announces Initiation of Phase III Part of Phase II/III Clinical Trial with IFX-1 in Severe COVID-19 Induced Pneumonia. Media-Rel 2020;.

    Media Release
  9. InflaRx. InflaRx Reports Q3 2020 Financial & Operating Results. Media-Rel 2020;.

    Media Release
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