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

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

Drug Name	Highest Phase	Originator
Vilobelimab - InflaRx	Phase III	InflaRx

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

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

Download Data (CSV)

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

Download Data (CSV)

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
07 Dec 2020	Other trial event	Last checked against European Clinical Trials Database record. European Clinical Trials Database Updated 07 Dec 2020
04 Nov 2020	Other trial event	Last checked against the ClinicalTrials.gov record. ClinicalTrials.gov: US National Institutes of Health 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
16 Sep 2020	Completion date	Planned End Date changed from 31 Dec 2020 to 31 Aug 2021. ClinicalTrials.gov: US National Institutes of Health Updated 21 Sep 2020
16 Sep 2020	Other trial event	Planned primary completion date changed from 31 Oct 2020 to 31 May 2021. ClinicalTrials.gov: US National Institutes of Health 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. European Clinical Trials Database 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) European Clinical Trials Database Updated 08 Apr 2020
07 Apr 2020	New trial record	New trial record ClinicalTrials.gov: US National Institutes of Health 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

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