Suspected or confirmed SARS-CoV-2 infection (confirmed by RNA-PCR) MedDRA version: 23.0 Level: PT Classification code 10051905 Term: Coronavirus infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Anakinra
Product Name: Anakinra
Product Code: L04AA14
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: Anakinra
CAS Number: 143090920
Current Sponsor
Sponsors
University of Manchester
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patient age 18 or above. • Clinically suspected/proven COVID-19. • Requiring organ support with one or more of: o Non-invasive or invasive ventilatory support o 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
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, personal/ professional legal representative or the attending physician are not committed to full active treatment. • Known condition resulting in ongoing immunosuppression including neutropenia (count < 1.5 x 109/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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Principal question/objective: Ascertain if anakinra administered subcutaneously will reach concentrations in the plasma (blood) that is thought to be effective and ascertain its effect on inflammation within the first week of treatment with the drug. ;Primary end point(s): Plasma IL-1Ra levels from Day 1 to Day 7 following administration of SC anakinra in patients with SARS-CoV-2 infection. Plasma IL-6 levels from Day 1 to Day 7 following administration of SC anakinra in patients with SARS-CoV-2 infection. ;Timepoint(s) of evaluation of this end point: Sampling at baseline, days 1, 3, 5, 7 and end of administration (day 14 or earlier) post-randomisation. ;Secondary Objective: Secondary objectives are: 1. To establish a relationship between concentrations of anakinra and markers of inflammation after SC and IV administration. 2. To determine and compare the pharmacokinetics and pharmacodynamics (amount and action of drug within the body) of SC and IV anakinra. 3. Obtain further safety information on patients with SARS-CoV-2 given SC anakinra. 4. To obtain and compare the feasibility of SC and IV administration. 5. To obtain preliminary data on efficacy and help to decide if a larger study of SC anakinra in COVID-19 patients is justified. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline with measurements performed every 3 days for markers including the following: IL-6, CRP, CXCL2, IL-1, IL-6 , IL-2, HMBG-1 and IL-33. 2. Safety endpoints include a) severe fatal or life-threatening serious adverse reactions (duration of IMP plus 30h from last dose). b) anaphylactic/anaphylactoid reactions (duration of IMP plus 30h from last dose). c) severe neutropenia (< 1.5 x 10^9 /L) (duration of IMP) d) IMP related severe laboratory abnormalities (duration of IMP) 3. Feasibility endpoints include protocol deviations in terms of timing and delivery of schedule medication. 4. 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). b) Ventilation free days (at 28 days). c) Status on the above ordinal scale (at 14 and 28 days). ;Timepoint(s) of evaluation of this end point: All endpoints will be evaluated up to day 14 unless otherwise specified above. | — |
Countries
United Kingdom
Contacts
Public ContactTim Felton
Manchester University NHS Foundation Trust
Outcome results
None listed