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

COVID-19 Clinical Trial

— INFLIXCOVID  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04922827
• Other study ID #: ZKSJ0137_INFLIXCOVID
• Secondary ID: 2021-002098-25
• Status: Completed
• Phase: Phase 2
• Start date: June 18, 2021
• Est. completion date: July 1, 2023

Study information

• Verified date: August 2022
• Source: Jena University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: July 1, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Infliximab
single intravenous administration of 5 milligrams/kilogram

Other:
• Standard of Care
Standard of Care

Locations

Country	Name	City	State
Germany	Universitätsklinikum Knappschaftskrankenhaus Bochum	Bochum
Germany	Klinikum Fulda	Fulda
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Jena University Hospital	Jena

Sponsors (3)

Lead Sponsor	Collaborator
Jena University Hospital	Celltrion, German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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	safety of Infliximab administration	frequencies of adverse events (AEs) and serious adverse events (SAEs)	up to 90 days after randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	assessment of the severity and frequency of organ failure: ventilation-free days	ventilation-free days until 28 days after randomization	day 28 after randomization
Secondary	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
Secondary	assessment of the severity and frequency of organ failure: vasopressor-free days	vasopressor-free days until 28 days after randomization	day 28 after randomization
Secondary	occurence of Acute Respiratory Distress Syndrome (ARDS)	rate of occurrence of ARDS until 28 days after randomization	day 28 after randomization
Secondary	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
Secondary	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
Secondary	length of stay: hospital	length of hospital stay up to day 28 after randomization	day 28 after randomization
Secondary	length of stay: intensive care unit	length of intensive care unit stay up to day 28 after randomization	day 28 after randomization
Secondary	mortality	mortality rates 14 and 90 days after randomization	day 14 and 90 after randomization
Secondary	health related quality of life: visual analogue scale	EQ5D-3L: visual analog scale value 90 days after randomization	day 90 after randomization
Secondary	health related quality of life: index	EQ5D-3L: index value 90 days after randomization	day 90 after randomization
Secondary	incidence of cardiomyopathy	incidence of cardiomyopathy 3 and/or 7 days after randomization	day 3 and 7 after randomization