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

NCT ID: NCT04922827

Last Updated: 2023-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-18
• Study Completion Date: 2023-07-01

Brief Summary

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.

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Infliximab + Standard of Care

Group Type: EXPERIMENTAL

Infliximab

Intervention Type: DRUG

single intravenous administration of 5 milligrams/kilogram

Standard of Care

Intervention Type: OTHER

Standard of Care

Standard of Care

Group Type: ACTIVE_COMPARATOR

Standard of Care

Intervention Type: OTHER

Standard of Care

Interventions

Infliximab

single intravenous administration of 5 milligrams/kilogram

Intervention Type: DRUG

Standard of Care

Standard of Care

Intervention Type: OTHER

Eligibility Criteria

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

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)

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

Celltrion

INDUSTRY

Sponsor Role: collaborator

Jena University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sina M Coldewey, Prof. Dr. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Department of Anaesthesiology and Intensive Care Medicine, Jena University Hospital

Andreas Stallmach, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital

Locations

Universitätsklinikum Knappschaftskrankenhaus Bochum

Bochum, , Germany

Klinikum Fulda

Fulda, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Jena University Hospital

Jena, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 36056419 (View on PubMed)

Other Identifiers

2021-002098-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ZKSJ0137_INFLIXCOVID

Identifier Type: -

Identifier Source: org_study_id