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Covid-19Phase 2JAKINCOVNCT04366232

Efficacy of Intravenous Anakinra and Ruxolitinib During COVID-19 Inflammation

A Phase 2 study testing Anakinra alone (stages 2b/3) and Anakinra and Ruxolitinib (overcome stage 3) in people with Covid-19, run by Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer at 3 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Covid-19
What is being tested?
Anakinra alone (stages 2b/3) and Anakinra and Ruxolitinib (overcome stage 3)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
3 sitesFrance
Study dates
19 Aug 2020to 2 Oct 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

3 sites in 1 country.

France3 sites

  • AP-HM, Hôpital de la Conception

    Marseille, Bouches-du-Rhône, 13005

  • Hôpital Sainte-Musse

    Toulon, VAR, 83000

  • Sainte Anne Teaching Military Hospital

    Toulon, Var, 83000

Other trials in France

About this study

Official title: Interleukin-1 (IL-1) and Interferon Gamma (IFNg) Inhibition During COVID 19 Inflammation: Randomized, Controlled Study Assessing Efficacy and Safety of Anakinra and Ruxolitinib

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.

Read the 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.

Conditions
Covid-19
Being tested
Anakinra alone (stages 2b/3), Anakinra and Ruxolitinib (overcome stage 3), Standard of care
Keywords
COVID, SARS-CoV-2, Anakinra, Ruxolitinib, IL-1 inhibitors, JAK inhibitors
Medical subject headings
COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anakinra alone (stages 2b/3)Drug

    Also called KINERET

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

  • Anakinra and Ruxolitinib (overcome stage 3)Drug

    Also called KINERET and JAKAVI

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

  • Standard of careOther

    Routine clinical care for Covid-19

Study groups in NCT04366232
Study groupRoleWhat they receive
Anakinra +/- RuxolitinibExperimentalAccording 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
Receives: Drug: Anakinra alone (stages 2b/3); Drug: Anakinra and Ruxolitinib (overcome stage 3)
Standard of careActive comparatorTreatment with drugs or procedures in routine clinical practice
Receives: Other: Standard of care

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 7 days from enrolment

Secondary outcomes (7)

  1. Duration of oxygen therapy (days)

    Number of days without mechanical ventilation

    Measured: 28 days from enrolment

  2. Number of intensive care units admissions

    Number of patients included in stage 2b

    Measured: 28 days from enrolment

  3. Number of days in intensive care units

    Number of days in intensive care units for patients managed in intensive care units

    Measured: 28 days from enrolment

  4. Mortality rate

    Mortality rate

    Measured: 28 days from enrolment

  5. Total number of days in hospital

    Total number of days in hospital

    Measured: 28 days from enrolment

  6. Organ failure score modification (Sepsis-related Organ Failure Assessment (SOFA) score)

    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.

    Measured: 28 days from enrolment

  7. Number of bacterial and/or fungal sepsis

    Number of bacterial and/or fungal sepsis

    Measured: 28 days from enrolment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Apr 2020
  2. Study start19 Aug 2020
  3. Primary completion2 Oct 2020
  4. Study completion2 Oct 2020

Why it stopped: investigator decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Assignment to one of two or more groups in parallel during the study No crossover
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04366232
Sponsor's protocol ID
2020-CHITS-003
Other IDs
2020-001963-10
Acronym
JAKINCOV
Status last verified
Dec 2020
First submitted
27 Apr 2020
Last updated
16 Dec 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32192578

  • 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.

    PubMed 32091533

  • 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.

    PubMed 28895072

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anakinra alone (stages 2b/3) and Anakinra and Ruxolitinib (overcome stage 3) in people with Covid-19, run by Centre Hospitalier Intercommunal de Toulon La Seyne sur Mer at 3 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: investigator decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Biological criteria (time frame: 7 days from enrolment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04366232, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2020.

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