- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04366232
Efficacy of Intravenous Anakinra and Ruxolitinib During COVID-19 Inflammation (JAKINCOV)
Interleukin-1 (IL-1) and Interferon Gamma (IFNg) Inhibition During COVID 19 Inflammation: Randomized, Controlled Study Assessing Efficacy and Safety of Anakinra and Ruxolitinib
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Two physiopathological phases exist during COVID-19 disease: The early phase is mainly induced by the virus itself. It is imperative not to decrease the immune host response during this phase by prohibiting the use of non steroidal anti-inflammatory drugs or corticosteroids at this stage and developing an anti-viral strategy. The late phase, around Day 7-9, depends only upon host response and is linked to an excessive inflammatory response with a major increase of inflammatory cytokines such as IL-6, MCP-1, GCSF indicative of IL-1b excess, as well as IP-10, MIP-1, indicative of IFNg signature, corresponding to a "cytokine storm". Clinical and biological features during Still's disease (complicated in 10% of cases with hemophagocytosic lymphohistiocytosis inducing cytopenia, hepatic insufficiency, major hyperferritinemia and multi-organ failure) are close to those reported during COVID-19 and underline physiopathological similarities.
Anakinra (KINERET) is an IL-1 pathway (IL-1ra) specific inhibitor that has been used for 15 years, also largely blocking IL-18 production. Adult Still's disease is very effectively treated with anakinra. During sepsis with hyperferritinemia, IL-1ra demonstrated patient survival improvement. Ruxolitinib (JAKAVI) inhibits the downstream IFNg pathway targeting JAK kinase receptor. It has recently proved its efficiency in hemophagocytosic lymphohistiocytosis refractory forms associated with a multi-organ failure.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Bouches-du-Rhône
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Marseille, Bouches-du-Rhône, France, 13005
- AP-HM, Hôpital de la Conception
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VAR
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Toulon, VAR, France, 83000
- Hôpital Sainte-Musse
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Var
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Toulon, Var, France, 83000
- Sainte Anne Teaching Military Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Confirmed respiratory tract SARS-coV-2 infection by at least one PCR on nasopharygeal sample or a bronchoalveolar lavage
Patient hospitalized with clinical, biological and radiological features corresponding to the following stages :
- Stage 2b: hypoxic pneumonia (respiratory frequency > 30/mn, Sa02 < 90 mmHg on room air) associated with a clear biological inflammatory syndrome (CRP > 150 mg/l)
- Stage 3: ARDS defined by a patient under mechanical ventilation with a ratio PaO2/FiO2 < 300 for more than 24h
- Evolved stage 3: ARDS according to previous definition associated with another organ failure or syndrome among:
- A state of shock with noradrenaline dosing > 3mg/h
- Acute kidney failure oligo-anuric or justifying extra-renal purification
- Hepatocellular insufficiency or coagulopathy with a V factor < 50%
- Myocarditis responsible for acute heart failure and or cardiogenic shock
- Hemophagocytic syndrome
- Hyperferritinemia > 5000 ng/mL
- Subject or legal representative having expressed written consent after information
- Subject affiliated to or entitled to a social security regimen
- Patient presenting in a life-threatening emergency situation that does not allow consent to be obtained
Exclusion Criteria:
- Pregnancy or lactation
- Absolute neutrophil count less than 1.5 x 109/L
- Hepatic transaminases AST or ALT greater than 5 times normal values
- Platelet count less than 50,000 per mm3
- Solid organ or hematopoietic stem cell transplant patients
- Patients treated with immunosuppressants or immunomodulators
- Use of oral corticosteroids chronically at doses greater than 10 mg prednisone equivalent per day for a non-COVID-19 related condition.
- Uncontrolled autoimmune disease
- Patients with active, suspected or known, uncontrolled systemic bacterial, viral (excluding COVID-19) or fungal infections
- Hypersensitivity to anakinra and/or ruxolitinib and their excipients
- Vaccinations with live attenuated vaccines in the month prior to inclusion
- Patients with severe pre-existing uncontrolled organ dysfunction (heart, liver or kidney failure)
- Persons deprived of liberty by judicial or administrative decision or major persons under a legal protection measure.
- Person in exclusion period of another research protocol for SARS-CoV-2 infection.
- Person not mastering enough French understanding and reading to be able to consent to participate in the study.
- Persons under psychiatric care pursuant to Articles A3112-1 and L3113-1 who are not covered by the provisions of Article L1121-8
- Every condition which, according to investigator, might increase and compromise the person security in case of study participation or might interfere with research results.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Standard of care
Treatment with drugs or procedures in routine clinical practice
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Routine clinical care for Covid-19
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Experimental: Anakinra +/- Ruxolitinib
According to clinical stage (gradual strategy):
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Anakinra 300 mg 1/d Intravenous 5 days then dose tapering
Other Names:
Anakinra 300 mg od Intravenous (maximum14 days) Ruxolitinib 5 mg bid per os (maximum 28 days)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Biological criteria
Time Frame: 7 days from enrolment
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At least 3 parameters are met including CRP and/or Ferritin among:
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7 days from enrolment
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Duration of oxygen therapy (days)
Time Frame: 28 days from enrolment
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Number of days without mechanical ventilation
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28 days from enrolment
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Number of intensive care units admissions
Time Frame: 28 days from enrolment
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Number of patients included in stage 2b
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28 days from enrolment
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Number of days in intensive care units
Time Frame: 28 days from enrolment
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Number of days in intensive care units for patients managed in intensive care units
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28 days from enrolment
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Mortality rate
Time Frame: 28 days from enrolment
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Mortality rate
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28 days from enrolment
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Total number of days in hospital
Time Frame: 28 days from enrolment
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Total number of days in hospital
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28 days from enrolment
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Organ failure score modification (Sepsis-related Organ Failure Assessment (SOFA) score)
Time Frame: 28 days from enrolment
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Organ failure score modification (Sepsis-related Organ Failure Assessment (SOFA) score); Sofa score's minimum and maximum values are 0 and 24, the lowest score corresponds to a better outcome.
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28 days from enrolment
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Number of bacterial and/or fungal sepsis
Time Frame: 28 days from enrolment
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Number of bacterial and/or fungal sepsis
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28 days from enrolment
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Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: David DELARBRE, MD, French Army Health Service
Publications and helpful links
General Publications
- Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020 Apr 7;323(13):1239-1242. doi: 10.1001/jama.2020.2648. No abstract available.
- Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
- Zalinger ZB, Elliott R, Weiss SR. Role of the inflammasome-related cytokines Il-1 and Il-18 during infection with murine coronavirus. J Neurovirol. 2017 Dec;23(6):845-854. doi: 10.1007/s13365-017-0574-4. Epub 2017 Sep 11.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- 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
- Inflammation
- Antirheumatic Agents
- Interleukin 1 Receptor Antagonist Protein
Other Study ID Numbers
- 2020-CHITS-003
- 2020-001963-10 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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