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SCIL-1Ra in COVID-19 Feasibility & PK/PD (SCIL_COV19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04462757
Recruitment Status : Terminated (Lack of patients in the trial population from which to recruit and lack of funding)
First Posted : July 8, 2020
Last Update Posted : April 30, 2021
Sponsor:
Information provided by (Responsible Party):
University of Manchester

Brief Summary:

The current COVID-19 pandemic is a worldwide healthcare crisis. Of concern is the large number of patients that are/will require mechanical ventilation, and the associated strain that this will place on healthcare resources. At present, there are no specific therapeutic interventions directed at COVID-19 infection. However, observational data suggest that there is a subgroup of patients that demonstrate a hyperinflammatory response in response to COVID-19 and have a higher requirement for Critical Care and higher mortality.

There is a strong case for the use of the naturally occurring anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) in these patients. Anakinra is a recombinant form of IL-1Ra that is licensed for clinical use. Success of use of anakinra in COVID-19 trials will be greatly enhanced by robust scientific evidence and established pharmacokinetics which inform the most effective dosing regimens. The latter is especially important when, as in the case of anakinra, drug supplies are limited, the drug has short half-life and clinical ease of application is critical.


Condition or disease Intervention/treatment Phase
COVID-19 Drug: Anakinra 100Mg/0.67Ml Inj Syringe Phase 2

Detailed Description:
The investigators plan a small trial of an existing drug in patients with COVID-19 at Salford Royal NHS Foundation Trust (SRFT) and Manchester Foundation Trust (MFT). The investigators will recruit patients with suspected or confirmed COVID-19 infection within 24 hours of being transfer in a Critical Care department. The investigators have been testing interleukin-1 receptor antagonist: IL-1Ra (known as Anakinra) for many years. Marketed as a treatment for rheumatoid arthritis and for some rare autoimmune diseases, we have shown Anakinra also reduces or blocks inflammation in a number of other conditions e.g. stroke and brain haemorrhage. The investigators have found it to be safe, easily administered and well tolerated. As part of the global response to the SARS-COV-2 pandemic, researchers have identified drugs that repurposing existing drugs. Anakinra has been proposed as a candidate therapy for COVID-19 and will be used in REMAP-CAP clinical trial as an intravenous (IV) therapy four times daily (qds). Whilst there is uncertainty about the therapeutic benefits, the investigators wish to explore the theory that they can achieve comparable concentrations in the blood using a subcutaneous (SC) injection twice daily (bd), as observed with IV therapy qds. We will randomise up to 40 patients to receive either SC Anakinra twice daily or IV Anakinra four-times daily for 14 days (or until discharge from CCU). They will measure changes in biomarkers in both groups and use the data to inform a mathematical model to simulate the effect the drug may have on the body. The aim is to the provide evidence that a lower dose SC Anakinra is as effective as higher dose IV.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Patients will be randomly assigned to one of two arms:-

  • Subcutaneous arm: 100mg anakinra SC will be administered subcutaneously at consistent times that are convenient and practical for the patients and research/nursing staff providing there is a minimum 8 hours and maximum 16 hours between administrations.
  • Intravenous arm: 100mg anakinra in 100mL 0.9% NaCl will be administered intravenously four times a day every 6 hours.
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: Subcutaneous and Intravenous IL-1Ra (Anakinra) in COVID-19 Infection - Feasibility & Pharmacokinetics/Pharmacodynamics Study
Actual Study Start Date : May 28, 2020
Actual Primary Completion Date : August 31, 2020
Actual Study Completion Date : December 23, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Anakinra

Arm Intervention/treatment
Active Comparator: Subcutaneous Arm
100mg anakinra SC will be administered subcutaneously at consistent times that are convenient and practical for the patients and research/nursing staff providing there is a minimum 8 hours and maximum 16 hours between administrations.
Drug: Anakinra 100Mg/0.67Ml Inj Syringe
100 mg interleukin-1 receptor antagonist (r-meth-Hu-IL-1Ra), anakinra; marketed as Kineret® in 0.67 mL prefilled syringe for single use
Other Name: Kineret

Active Comparator: Intravenous Arm
100mg anakinra in 100mL 0.9% NaCl will be administered intravenously four times a day every 6 hours.
Drug: Anakinra 100Mg/0.67Ml Inj Syringe
100 mg interleukin-1 receptor antagonist (r-meth-Hu-IL-1Ra), anakinra; marketed as Kineret® in 0.67 mL prefilled syringe for single use
Other Name: Kineret




Primary Outcome Measures :
  1. Plasma IL-1Ra levels [ Time Frame: 1 week ]
    Plasma IL-1Ra levels from Day 1 to Day 7 following administration of SC anakinra in patients with SARS-CoV-2

  2. Plasma IL-6 levels [ Time Frame: 1 week ]
    Plasma IL-6 levels from Day 1 to Day 7 following administration of SC anakinra in patients with SARS-CoV-2


Secondary Outcome Measures :
  1. Plasma markers [ Time Frame: 2 weeks ]
    Plasma markers including IL-6 from Day 1 to Day 14 in all participants

  2. Plasma markers [ Time Frame: 2 weeks ]
    Plasma markers including CRP from Day 1 to Day 14 in all participants

  3. Plasma markers [ Time Frame: 2 weeks ]
    Plasma markers including CXCL9 from Day 1 to Day 14 in all participants

  4. Plasma markers [ Time Frame: 2 weeks ]
    Plasma markers including IL-1 from Day 1 to Day 14 in all participants

  5. Plasma markers [ Time Frame: 2 weeks ]
    Plasma markers including IL-2 from Day 1 to Day 14 in all participants

  6. Plasma markers [ Time Frame: 2 weeks ]
    Plasma markers including HMBG-1 from Day 1 to Day 14 in all participants

  7. Plasma markers [ Time Frame: 2 weeks ]
    Plasma markers including IL-33 from Day 1 to Day 14 in all participants

  8. Safety Endpoints related to the Serious adverse reactions of the IMP [ Time Frame: 2 weeks ]

    Safety endpoints include:

    a. Severe fatal or life-threatening serious adverse reactions (duration of IMP plus 30h from last dose).


  9. Safety Endpoints related to the anaphylactic reactions of the IMP [ Time Frame: 2 weeks ]

    Safety endpoints include:

    b. Anaphylactic/anaphylactoid reactions (duration of IMP plus 30h from last dose).


  10. Safety Endpoints related to neutropenia caused by the IMP [ Time Frame: 2 weeks ]

    Safety endpoints include:

    c. Severe neutropenia (< 1.5 x 109 /L) (duration of IMP)


  11. Safety Endpoints related to any severe laboratory abnormalities [ Time Frame: 2 weeks ]

    Safety endpoints include:

    d. IMP related severe laboratory abnormalities (duration of IMP)


  12. Feasibility endpoints related to IMP and deviations [ Time Frame: 2 weeks ]
    Feasibility endpoints include protocol deviations in terms of timing and delivery of scheduled medication.

  13. Exploratory Data on Clinical efficacy by time to recovery [ Time Frame: 4 weeks ]

    Exploratory data on clinical efficacy as defined by:

    a. Time to recovery defined by hospital discharge or improvement of two points on the ordinal scale: not hospitalised; hospitalised without need for supplemental oxygen; requiring supplemental oxygen; requiring HFNC or non-invasive mechanical ventilation; requiring ECMO or mechanical intervention; dead. Improvement mechanical ventilation (from recruitment to time of ventilation)


  14. Exploratory Data on Clinical efficacy [ Time Frame: 4 weeks ]

    Exploratory data on clinical efficacy as defined by:

    b. Ventilation free days (at 28 days)


  15. Exploratory Data on Clinical efficacy of the ordinal scale [ Time Frame: 4 weeks ]

    Exploratory data on clinical efficacy as defined by:

    c. Status on the above ordinal scale (at 14 and 28 days)




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient age 18 or above.
  • Clinically suspected/proven COVID-19.
  • Requiring organ support with one or more of:
  • Non-invasive or invasive ventilatory support
  • Receiving infusion of vasopressor or inotropes or both.
  • No concomitant health problems that, in the opinion of the PI or designee in agreement with the treating clinician, would interfere with participation, administration of study drug or assessment of outcomes including safety.

Exclusion Criteria:

  • More than 24h has elapsed since CCU admission.
  • Death is deemed to be imminent and inevitable during the next 24h.
  • One or more of: the patient, substitute decision-maker or the attending physician are not committed to full active treatment.
  • Known condition resulting in ongoing immunosuppression including neutropenia (count < 1.5 x 10^9/L) prior to hospitalisation, malignancy, latent tuberculosis or chronic liver disease (if known).
  • Previous or current treatment with anakinra or medication suspected of interacting with anakinra, listed in the drug SmPC, known at the time of trial entry or previous participation in this trial.
  • Known to have received active treatment in a clinical trial of an investigational immunomodulatory agent (not including corticosteroids) within 30 days prior to study entry.
  • Known to be pregnant or breast feeding or inability to reliably confirm that the patient is not pregnant.
  • Known allergy to anakinra or any of the excipients listed in the drug SmPC
  • Known allergy to other products that are produced by DNA technology using the micro-organism E. coli (e.g. Escherichia coli derived protein).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04462757


Locations
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United Kingdom
Manchester Univesity NHS Foundation Trust
Manchester, United Kingdom, M13 9WL
Salford Royal NHS Foundation Tust
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
University of Manchester
Investigators
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Principal Investigator: Timothy Felton, Dr University of Manchester
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Responsible Party: University of Manchester
ClinicalTrials.gov Identifier: NCT04462757    
Other Study ID Numbers: 282110
2020-001636-95 ( EudraCT Number )
First Posted: July 8, 2020    Key Record Dates
Last Update Posted: April 30, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents