E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Stroke - loss of neurological function caused by a blockage in the blood vessel |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061256 |
E.1.2 | Term | Ischaemic stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
To determine the effect of a specific type of anti-inflammatory drug (Interleukin-1 receptor antagonist; IL-1Ra), which is administered as an injection into the skin, have on levels of an inflammation-causing protein (Interleukin-6; IL-6) in blood samples taken between 6 hours and 5-7 days after the onset of a stroke.
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E.2.2 | Secondary objectives of the trial |
To determine the effect of SC IL-1Ra on other markers of inflammation in the blood.
To determine the effect of SC IL-1Ra on outcome (level of disability and length of hospital stay) at 3 months following stroke.
To obtain further feasibility and safety data in patients given SC IL-1Ra.
To examine how the body's immune system is affected after stroke, specifically if there is a reduction in the body's ability to fight infection.
Using blood samples obtained from the recruited stroke patients and comparing it to blood samples obtained from healthy volunteers we will:
i) Confirm whether the ability of specific blood cells (leucocyte) to respond to an infection is dampened down (suppressed) in stroke patients compared to age and sex matched healthy volunteers.
ii) Establish whether the suppression is reversed in the stroke patients treated with SC IL-1Ra
iii) Identify whether a hormone produced by the body called cortisol may play a role in immune suppression, and if |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
PATIENT GROUP •Patients with confirmed ischaemic stroke who are admitted to the Comprehensive Stroke Centre at Salford Royal NHS Foundation Trust (SRFT) where consent can be obtained and drug administered within 6 hours. •National Institutes of Health stroke scale (NIHSS) score between 4 – 26. •No concomitant health problems that, in the opinion of the Principal Investigator (PI) or designee, would interfere with participation, administration of study treatment or assessment of outcomes including safety, for example, pre-existing malignancy. •Renal function within normal limits (< 177 µmol/l). •Willing and able to give informed consent or consent available from a patient representative (personal-legal) for study inclusion including agreement in principle to receive study intervention and undergo all study assessments. •Aged 18 years or above.
HEALTHY VOLUNTEERS (recruited to provide a one-off 20ml blood sample only) •Between 18 and 80 years, in good health.
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E.4 | Principal exclusion criteria |
PATIENT GROUP •Unconfirmed or uncertain diagnosis of ischaemic stroke or rapid improving symptoms. •Haemorrhagic stroke. •NIHSS <4 or >26 •Known allergy to E. coli or any of the constituents of the study medication as established from the patient themselves, reliable representative and clinical records. •Previous or concurrent treatment with recombinant IL-1Ra known at the time of study entry. •Previous or current treatment with medication suspected of interacting with recombinant IL-1Ra, such as TNF-α inhibitors. •Known to have participated in a clinical trial of an investigational agent or device in the previous 30 days or for the period determined by the protocol of the study the patient has taken part in. •Known or planned pregnancy (pregnancy test to be performed in women of child-bearing potential) or breast-feeding. •Clinically significant concurrent medical condition, at the PI’s (or designee’s) discretion, which could affect the safety, tolerability, or efficacy in this study. •Previous inclusion in the current study (known prior to inclusion). •Evidence of current infection or infection within the past 4 wk. •Inability or unwillingness of patient or patient’s personal representative to give written informed consent.
HEALTHY VOLUNTEERS (recruited to provide a one-off 20ml blood sample only to act as controls to study participants - no drug will be administered to healthy volunteers) •Current acute medical problems or taking medication for chronic conditions.
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E.5 End points |
E.5.1 | Primary end point(s) |
Effect of SC IL-1Ra on levels of IL-6 within 3 days of stroke onset |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Within 3 days of stroke onset |
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E.5.2 | Secondary end point(s) |
Effect of SC IL-1Ra on levels of IL-6 within 5-7 days of stroke Effect of SC IL-1Ra on other inflammatory biomarkers Effect of SC IL-1Ra on clinical outcome at 3 months following ischaemic stroke To obtain further feasibility and safety data in patients given SC IL-1Ra. To determine the pattern of immune suppression, the effect of IL-1Ra and impact of cortisol, following stroke, compared with age-sex matched healthy volunteers, and if there is any relationship with infection. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
90 days (3 months) from onset of stroke |
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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 | No |
E.6.7 | Pharmacodynamic | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | 1 |
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 | Yes |
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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The definition of the end of the trial will be the last patient assessment in the intervention stage of the patient-participant study. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 30 |