Efficacy of Intravenous Anakinra and Ruxolitinib During COVID-19 Inflammation

NCT04366232 | Terminated Phase 2 DMC

• 2 other identifiers: 2020-CHITS-0032020-001963-10
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

Brief Summary

During SARS-Cov2 infection with serious respiratory implication and high systemic inflammation level, intravenous ANAKINRA alone or associated with RUXOLITINIB for severe cases might reduce inappropriate systemic inflammatory response, improve breathing and decrease occurrence or duration of ARDS and associated mortality.

Conditions

Covid-19

Keywords

COVID; SARS-CoV-2; Anakinra; Ruxolitinib; IL-1 inhibitors; JAK inhibitors

Outcome Measures

Primary Outcomes (1)

• Biological criteria

  At least 3 parameters are met including CRP and/or Ferritin among: 1. CRP: decrease \> 50% 2. Ferritinemia: decrease \> 1/3 3. Serum creatinine: decrease \> 1/3 4. AST/ALT: decrease \> 50% 5. Eosinophils \> 50 /mm3 6. Lymphocytes \> 1000 /mm3

  7 days from enrolment

Secondary Outcomes (7)

• Duration of oxygen therapy (days)

  28 days from enrolment

• Number of intensive care units admissions

  28 days from enrolment

• Number of days in intensive care units

  28 days from enrolment

• Mortality rate

  28 days from enrolment

• Total number of days in hospital

  28 days from enrolment

Study Arms (2)

Anakinra +/- Ruxolitinib

EXPERIMENTAL

According to clinical stage (gradual strategy): * Stage 2b or 3 : Anakinra 300 mg IV * Overcome stage 3 : Anakinra 300 mg IV and Ruxolitinib 5 mg x 2

Drug: Anakinra alone (stages 2b/3); Drug: Anakinra and Ruxolitinib (overcome stage 3)

Standard of care

ACTIVE COMPARATOR

Treatment with drugs or procedures in routine clinical practice

Other: Standard of care

Interventions

Anakinra alone (stages 2b/3) DRUG

Anakinra 300 mg 1/d Intravenous 5 days then dose tapering

Also known as: KINERET

Anakinra +/- Ruxolitinib

Anakinra and Ruxolitinib (overcome stage 3) DRUG

Anakinra 300 mg od Intravenous (maximum14 days) Ruxolitinib 5 mg bid per os (maximum 28 days)

Also known as: KINERET and JAKAVI

Anakinra +/- Ruxolitinib

Standard of care OTHER

Routine clinical care for Covid-19

Standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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 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.

Sponsors & Collaborators

• Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer: lead
• Hôpital d'instruction des armées Sainte-Anne: collaborator
• Assistance Publique Hopitaux De Marseille: collaborator

Study Sites (3)

AP-HM, Hôpital de la Conception

Marseille, Bouches-du-Rhône, 13005, France

Location

Hôpital Sainte-Musse

Toulon, VAR, 83000, France

Location

Sainte Anne Teaching Military Hospital

Toulon, Var, 83000, France

Location

Related Publications (3)

• 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.

  PMID: 32192578 RESULT

• 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.

  PMID: 32091533 RESULT

• 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.

  PMID: 28895072 RESULT

MeSH Terms

Conditions

COVID-19

Interventions

Interleukin 1 Receptor Antagonist Protein; ruxolitinib; Standard of Care

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• David DELARBRE, MD

  French Army Health Service

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Assignment to one of two or more groups in parallel during the study No crossover

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: April 28, 2020
• Study Start: August 19, 2020
• Primary Completion: October 2, 2020
• Study Completion: October 2, 2020
• Last Updated: December 16, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3)