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

NCT04462757 | Terminated Phase 2

• 2 other identifiers: 2821102020-001636-95
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

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.

Conditions

COVID-19

Outcome Measures

Primary Outcomes (2)

• 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

  1 week

• 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

  1 week

Secondary Outcomes (15)

• Plasma markers

  2 weeks

• Plasma markers

  2 weeks

• Plasma markers

  2 weeks

• Plasma markers

  2 weeks

• Plasma markers

  2 weeks

Study Arms (2)

Subcutaneous Arm

ACTIVE COMPARATOR

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

Intravenous Arm

ACTIVE COMPARATOR

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

Interventions

Anakinra 100Mg/0.67Ml Inj Syringe DRUG

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

Also known as: Kineret

Intravenous Arm; Subcutaneous Arm

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Manchester: lead

Study Sites (2)

Manchester Univesity NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

Salford Royal NHS Foundation Tust

Salford, M6 8HD, United Kingdom

Location

MeSH Terms

Conditions

COVID-19

Interventions

Interleukin 1 Receptor Antagonist Protein

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

Study Officials

• Timothy Felton, Dr

  University of Manchester

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: 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.

Study Record Dates

• First Submitted: June 12, 2020
• First Posted: July 8, 2020
• Study Start: May 28, 2020
• Primary Completion: August 31, 2020
• Study Completion: December 23, 2020
• Last Updated: April 30, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)