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

Trial Profile

A Pragmatic Adaptive Open Label, Randomized 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: 21 Jul 2020

At a glance

  • Drugs IFX 1 (Primary)
  • Indications COVID 2019 infections; Pneumonia
  • Focus Registrational; Therapeutic Use
  • Acronyms PANAMO
  • Sponsors InflaRx
  • Most Recent Events

    • 21 Jul 2020 According to an InflaRx media release, phase III part of this study is subject to regulatory approval.
    • 21 Jul 2020 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.
    • 21 Jul 2020 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.

Trial Overview

Purpose

This is a pragmatic, adaptive, open-label, randomized, multicenter phase II/III study consisting of two parts: Phase II and Phase III. In both study parts, patients will be randomized to two treatment arms (Arm A: best supportive care [BSC] + IFX-1; Arm B: BSC alone). After all patients are treated in Phase II, an interim analysis will be performed to assess the clinical benefit of the treatment using the assessed clinical parameters. Phase II part of the trial was exploratory in and was not powered to show statistically significant differences in clinical endpoints. Relative change (%) from baseline to day 5 in the oxygenation index, chosen as the primary endpoint for the Phase II part, showed a large variability and dependency on patient positioning and intubation status which excludes this endpoint from being used in a confirmatory study.
Phase III part is an adequately powered, placebo-controlled, double blinded, using 28-day all-cause mortality as the primary endpoint, an accepted regulatory primary endpoint for critical care studies.

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

28-day all-cause mortality (phase III endpoint)

Other Endpoints

Patients achieving early response

description: Number of patients (%) achieving an Early Response
time_frame: Baseline to Day 7 [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Pneumonia treatment severe

Subjects

  • Subject Type patients
  • Number

    Planned: 130

  • 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-CoV2 infection confirmation (tested positive in last 14 days or test results to be obtained within 24h after enrollment, both with locally available test system).

Patient Exclusion Criteria

- Known history of COPD - Received new other biologic treatment attempt for COVID-19 in the past 14 days - Received treatment with a viral replication inhibitor in past 3 days - Received organ or bone marrow transplantation in past 3 months - Known mechanically resuscitation in past 14 days - Known severe congestive heart failure (NYHA-Class III - IV)

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 Oct 2020

  • End Dates

    Planned : 31 Dec 2020

Other Details

  • Design multicentre; open; parallel; prospective; randomised
  • Phase of Trial Phase II/III
  • Location Europe; Netherlands; South America; USA
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
IFX 1Primary Drug Intravenous Infusion

Arm A: BSC + IFX-1

Drug: Best supportive Care (BSC) + IFX-1 (Best supportive care [BSC] + IFX-1)

Arm B : BSC only

Drug: Best supportive care only (Best supportive care only)

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 IFX 1 treatment group was 13% (2 out of 15) versus 27% (4 out of 15) in the control group. In a IFX 1 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 IFX 1 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 IFX 1 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, IFX 1 treatment was well tolerated. There was one death in IFX 1 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 IFX 1 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
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
10 May 2020 Other trial event Last checked against Eudra record. Updated 10 May 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
17 Apr 2020 Other trial event Last checked against the ClinicalTrials.gov record. Updated 17 Apr 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 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
  6. InflaRx. InflaRx Reports Full Year 2019 Financial & Operating Results. Media-Rel 2020;.

    Media Release
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