E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Suspected or confirmed SARS-CoV-2 infection (confirmed by RNA-PCR) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10051905 |
E.1.2 | Term | Coronavirus infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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).
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E.5 End points |
E.5.1 | 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.
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E.5.1.1 | 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.
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E.5.2 | 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).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All endpoints will be evaluated up to day 14 unless otherwise specified above. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
same IMP different route of administration |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 1 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 21 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 27 |