Infliximab in the Treatment of Patients With Severe COVID-19 Disease (INFLIXCOVID)

A Randomized, Controlled, Multicenter, Open Label Phase II Clinical Study to Evaluate Infliximab in the Treatment of Patients With Severe COVID-19 Disease

In this trial, patients that are severely affected by the disease COVID-19 will either receive infliximab, an anti-inflammatory drug, or standard therapy. Infliximab is a drug that inhibits inflammation by blocking a molecule called TNFα. The patients receive the drug via an infusion into a vein. The primary goal of this trial is to see whether the drug infliximab affects how many people died from COVID-19 after 28 days by comparing patients receiving the drug in addition to standard therapy with patients only receiving standard therapy.

Furthermore, this trial will look at whether the drug is safe to use in these patients, whether it has an effect on the inflammation and whether it can affect how ill patients are after surviving the disease.

The trial is conducted in more than one hospital. As COVID-19 is responsible for a global pandemic, positive results of this trial could affect patients, healthcare and economic systems worldwide.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Other: Standard of Care; Drug: Infliximab

Detailed Description

The long-term goal of this research project is to develop a new pharmacological treatment strategy for patients with COVID-19. Its primary aim is the assessment of efficacy and safety of the TNFα antibody infliximab in the treatment of patients with severe COVID-19 in a phase-2 trial. Infliximab is expected to attenuate the inflammatory reaction in patients and thereby positively influence the course of the disease.

The primary endpoint is the difference in 28-day-mortality of patients with severe COVID-19 receiving one dose of 5mg per kg body weight infliximab intravenously in addition to the standard of care (intervention group) compared with patients receiving standard of care (control group).

Secondary aims of this trial include the assessment of the safety of the TNFα antibody infliximab in the treatment of patients with severe COVID-19, of its effect on an excessive immune response and of its effect on the morbidity and prognosis as well as the characterization of the analytical cohorts.

The multi-centre design facilitates the transferability of study results to hospitals of similar healthcare level. Should infliximab prove to be superior to standard therapy, this could be reflected in a reduced disease severity and mortality.

The results of this study could influence the therapy of patients with COVID-19 worldwide and affect the course of the disease worldwide, as infliximab is approved by several international drug agencies and globally available. Due to the high incidence of COVID-19 worldwide and the immense effects of the pandemic on societies, health care and economic systems, any progress in the treatment of this new disease would constitute a great success. This would not only impact individual patients but also have positive economic effects.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Bochum, Germany, 44892
    • Universitätsklinikum Knappschaftskrankenhaus Bochum
  • Fulda, Germany, 36043
    • Klinikum Fulda
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Jena, Germany, 07747
    • Jena University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥ 18 years
• Infection with SARS-CoV-2 (virus detection by means of a PCR test not older than 72 hours)
• Bipulmonary infiltrates (detection by means of X-rays or computed tomography)
• COVID inflammation score ≥ 10
• Ferritin concentration (serum or plasma) ≥ 500 ng / ml
• Arterial oxygen saturation ≤ 93% when breathing room air
• written informed consent from the patient
• Potentially childbearing women: negative pregnancy test

Exclusion Criteria (in medical history):

Contraindications study medication:

• Hypersensitivity to the active substance infliximab (or any of the other ingredients of the medicine) or to other murine proteins
• active or latent tuberculosis
• acute or chronic hepatitis B
• severe infections such as invasive fungal infections, bacterial sepsis, or abscesses
• opportunistic infections (e.g. pneumocystosis, listeriosis)
• moderate or severe heart failure (NYHA class III / IV)
• Immunosuppression (e.g. organ transplantation, AIDS, leukopenia)
• Malignancies or lymphoproliferative diseases or chemotherapy within the last 4 weeks
• Multiple sclerosis or peripheral demyelinating diseases, including the Guillain-Barré syndrome
• Treatment with other biologics for therapy for approved indications of infliximab (e.g. for rheumatoid arthritis, Crohn's disease, ulcerative colitis, ankylosing spondylitis, psoriatic arthritis, psoriasis)

Further exclusion criteria:

• Autoimmune disease with biologics therapy
• Current treatment with TNF antibodies, convalescent plasma, bamlanivimab, or other experimental treatments for COVID-19
• High-flow oxygen therapy, non-invasive / invasive ventilation (WHO-COVID-19 PROGRESSION Scale > 5)
• pre-existing long-term ventilation or home oxygen therapy
• Child-Pugh C liver cirrhosis
• Pregnancy or breastfeeding
• Patients with a life expectancy < 90 days due to other medical conditions
• Limitation or discontinuation of therapy (e.g. refusal of artificial ventilation)
• Participation in another interventional study
• Previous participation in this study
• Interdependence between the patient and the coordinating investigator or other members of the study team

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard of Care	Other: Standard of Care; Standard of Care
Experimental: Infliximab + Standard of Care	Other: Standard of Care; Standard of Care; Drug: Infliximab; single intravenous administration of 5 milligrams/kilogram

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28-day mortality	differences in mortality-rates between both study arms (Infliximab + Standard of Care vs. Standard of Care) 28 days after randomisation	28 days after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safety of Infliximab administration	frequencies of adverse events (AEs) and serious adverse events (SAEs)	up to 90 days after randomization
assessment of the effect of infliximab on an excessive immune response in patients with COVID-19: Interleukin 6	change in the interleukin-6 (IL-6) concentration in the blood from randomization to day 7 and day 14 after randomization	day 7 and day 14 after randomization
assessment of the effect of infliximab on an excessive immune response in patients with COVID-19: ferritin	change in the ferritin concentration in the blood from randomization to day 7 and day 14 after randomization	day 7 and day 14 after randomization
assessment of the effect of infliximab on an excessive immune response in patients with COVID-19: lymphocyte count	change in the lymphocyte count from randomization to day 7 and day 14 after randomization	day 7 and day 14 after randomization
assessment of the severity and frequency of organ failure: ventilation-free days	ventilation-free days until 28 days after randomization	day 28 after randomization
assessment of the severity and frequency of organ failure: renal replacement therapy-free days	renal replacement therapy-free days until 28 days after randomization	day 28 after randomization
assessment of the severity and frequency of organ failure: vasopressor-free days	vasopressor-free days until 28 days after randomization	day 28 after randomization
occurence of Acute Respiratory Distress Syndrome (ARDS)	rate of occurrence of ARDS until 28 days after randomization	day 28 after randomization
WHO-COVID-19-Progression Scale	WHO-COVID-19-Progression Scale on day 7, 14 and 28 after randomization	day 7, 14 and 28 after randomization
rate of admission to the intensive care unit	rate of admission to the intensive care unit after randomization up to day 28	day 28 after randomization
length of stay: hospital	length of hospital stay up to day 28 after randomization	day 28 after randomization
length of stay: intensive care unit	length of intensive care unit stay up to day 28 after randomization	day 28 after randomization
mortality	mortality rates 14 and 90 days after randomization	day 14 and 90 after randomization
health related quality of life: visual analogue scale	EQ5D-3L: visual analog scale value 90 days after randomization	day 90 after randomization
health related quality of life: index	EQ5D-3L: index value 90 days after randomization	day 90 after randomization
incidence of cardiomyopathy	incidence of cardiomyopathy 3 and/or 7 days after randomization	day 3 and 7 after randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
collection and storage of blood and urine sample	collection and storage of blood and urine sample for the investigation of translational research questions by analysing biomarkers of organ, metabolic and immunological function and regulation	day 3, 7 and 14 after randomization
comparison with other cohorts	comparison of the course of disease of patients with severe COVID-19 and previously generated datasets from patients with sepsis and health subjects	up to day 90 after randomization

Collaborators and Investigators

• Sponsor: Jena University Hospital
• Collaborators: German Federal Ministry of Education and Research; Celltrion
• Investigators: Principal Investigator: Sina M Coldewey, Prof. Dr. Dr. med., Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital; Principal Investigator: Andreas Stallmach, Prof. Dr. med., Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital

Publications and helpful links

General Publications

• Coldewey SM, Neu C, Bloos F, Baumbach P, Schumacher U, Bauer M, Reuken P, Stallmach A. Infliximab in the treatment of patients with severe COVID-19 (INFLIXCOVID): protocol for a randomised, controlled, multicentre, open-label phase II clinical study. Trials. 2022 Sep 2;23(1):737. doi: 10.1186/s13063-022-06566-5.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2021
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): July 1, 2023

Study Registration Dates

• First Submitted: June 10, 2021
• First Submitted That Met QC Criteria: June 10, 2021
• First Posted (Actual): June 11, 2021

Study Record Updates

• Last Update Posted (Actual): July 12, 2023
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Tumor Necrosis Factor Inhibitors; Infliximab
• Other Study ID Numbers: ZKSJ0137_INFLIXCOVID; 2021-002098-25 (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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No