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COVID-19Phase 2SCIL_COV19NCT04462757

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

A Phase 2 study testing Anakinra 100Mg/0.67Ml Inj Syringe in people with COVID-19, run by University of Manchester at 2 sites in United Kingdom.

Terminated

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

Official record
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Trial 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. 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 100Mg/0.67Ml Inj Syringe
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5 participants
Where
2 sitesUnited Kingdom
Study dates
28 May 2020to 23 Dec 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

  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • Manchester Univesity NHS Foundation Trust

    Manchester, M13 9WL

  • Salford Royal NHS Foundation Tust

    Salford, M6 8HD

Other trials in United Kingdom

About this study

Official title: Subcutaneous and Intravenous IL-1Ra (Anakinra) in COVID-19 Infection - Feasibility & Pharmacokinetics/Pharmacodynamics Study

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.

Read the 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.

Conditions
COVID-19
Being tested
Anakinra 100Mg/0.67Ml Inj Syringe
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 100Mg/0.67Ml Inj SyringeDrug

    Also called Kineret

    100 mg interleukin-1 receptor antagonist (r-meth-Hu-IL-1Ra), anakinra; marketed as Kineret® in 0.67 mL prefilled syringe for single use

Study groups in NCT04462757
Study groupRoleWhat they receive
Subcutaneous ArmActive comparator100mg 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.
Receives: Drug: Anakinra 100Mg/0.67Ml Inj Syringe
Intravenous ArmActive comparator100mg anakinra in 100mL 0.9% NaCl will be administered intravenously four times a day every 6 hours.
Receives: Drug: Anakinra 100Mg/0.67Ml Inj Syringe

What is being measured

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

  1. Plasma IL-1Ra levels

    Plasma IL-1Ra levels from Day 1 to Day 7 following administration of SC anakinra in patients with SARS-CoV-2

    Measured: 1 week

  2. Plasma IL-6 levels

    Plasma IL-6 levels from Day 1 to Day 7 following administration of SC anakinra in patients with SARS-CoV-2

    Measured: 1 week

Secondary outcomes (15)

  1. Plasma markers

    Plasma markers including IL-6 from Day 1 to Day 14 in all participants

    Measured: 2 weeks

  2. Plasma markers

    Plasma markers including CRP from Day 1 to Day 14 in all participants

    Measured: 2 weeks

  3. Plasma markers

    Plasma markers including CXCL9 from Day 1 to Day 14 in all participants

    Measured: 2 weeks

  4. Plasma markers

    Plasma markers including IL-1 from Day 1 to Day 14 in all participants

    Measured: 2 weeks

  5. Plasma markers

    Plasma markers including IL-2 from Day 1 to Day 14 in all participants

    Measured: 2 weeks

  6. Plasma markers

    Plasma markers including HMBG-1 from Day 1 to Day 14 in all participants

    Measured: 2 weeks

  7. Plasma markers

    Plasma markers including IL-33 from Day 1 to Day 14 in all participants

    Measured: 2 weeks

  8. Safety Endpoints related to the Serious adverse reactions of the IMP

    Safety endpoints include:

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

    Measured: 2 weeks

  9. Safety Endpoints related to the anaphylactic reactions of the IMP

    Safety endpoints include:

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

    Measured: 2 weeks

  10. Safety Endpoints related to neutropenia caused by the IMP

    Safety endpoints include:

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

    Measured: 2 weeks

  11. Safety Endpoints related to any severe laboratory abnormalities

    Safety endpoints include:

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

    Measured: 2 weeks

  12. Feasibility endpoints related to IMP and deviations

    Feasibility endpoints include protocol deviations in terms of timing and delivery of scheduled medication.

    Measured: 2 weeks

  13. Exploratory Data on Clinical efficacy by time to recovery

    Exploratory data on clinical efficacy as defined by:

    1. 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)

    Measured: 4 weeks

  14. Exploratory Data on Clinical efficacy

    Exploratory data on clinical efficacy as defined by:

    1. Ventilation free days (at 28 days)

    Measured: 4 weeks

  15. Exploratory Data on Clinical efficacy of the ordinal scale

    Exploratory data on clinical efficacy as defined by:

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

    Measured: 4 weeks

Timeline

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

  1. First posted8 Jul 2020
  2. Study start28 May 2020
  3. Primary completion31 Aug 2020
  4. Study completion23 Dec 2020

Why it stopped: Lack of patients in the trial population from which to recruit and lack of funding

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
Health services research
Allocation
Randomised
Intervention model
Parallel groups
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)
Enrolment
5 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04462757
Sponsor's protocol ID
282110
Other IDs
2020-001636-95
Acronym
SCIL_COV19
Status last verified
Apr 2021
First submitted
12 Jun 2020
Last updated
30 Apr 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Anakinra 100Mg/0.67Ml Inj Syringe in people with COVID-19, run by University of Manchester at 2 sites in United Kingdom.

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 6 inclusion and 9 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 30 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. 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: Lack of patients in the trial population from which to recruit and lack of funding). 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?

Plasma IL-1Ra levels (time frame: 1 week). The study lists 2 primary outcomes in all. 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 NCT04462757.

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 30 Apr 2021.

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