<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03249207</url>
  </required_header>
  <id_info>
    <org_study_id>R121178</org_study_id>
    <nct_id>NCT03249207</nct_id>
  </id_info>
  <brief_title>SC IL-1Ra in SAH - Phase III Trial (SCIL)</brief_title>
  <acronym>SCIL</acronym>
  <official_title>Does Interleukin-1 Receptor Antagonist Improve Outcome Following Aneurysmal Subarachnoid Haemorrhage (aSAH)? A Phase III Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Manchester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute for Health Research, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Clinical Trials Unit, Manchester</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Northern Care Alliance NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Manchester</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase III trial will establish whether IL-1Ra, with sub-cutaneous (SC) administration&#xD;
      twice daily for up to 21 days post aneurysmal subarachnoid haemorrhage (aSAH), improves&#xD;
      clinical outcome as measured by ordinal shift in mRS at 6 months.&#xD;
&#xD;
      Patients with SAH transferred to a neurosurgical centre will be identified and approached for&#xD;
      study participation. Following consent, patients will be randomised to receive either IL-1Ra&#xD;
      or placebo for a maximum of 21 days from onset of symptoms. Patients who are found to be&#xD;
      non-aneurysmal following randomisation will be withdrawn from the study treatment. Blood&#xD;
      samples for plasma IL-6 will be obtained prior to randomisation and at day 3-5 post&#xD;
      randomisation for IL-6 &amp; IL-1 measurement. Safety will be measured at 30 days post&#xD;
      randomisation and outcome assessed at 6 months post randomisation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 11, 2018</start_date>
  <completion_date type="Anticipated">September 2024</completion_date>
  <primary_completion_date type="Anticipated">April 2024</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ordinal shift in modified Rankin Score (mRS)</measure>
    <time_frame>6 months post randomisation</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measurement of mood using HADS</measure>
    <time_frame>6 months post randomisation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of fatigue using Fatigue score</measure>
    <time_frame>6 months post randomisation</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measurement of quality of life using EQ-5D-5L score</measure>
    <time_frame>6 months post randomisation</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Subarachnoid Hemorrhage</condition>
  <arm_group>
    <arm_group_label>IL-1Ra twice daily</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo twice daily</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IL-1Ra</intervention_name>
    <description>Doses to be administered subcutaneously (SC) twice daily (12 hourly) starting within 72 hours of ictus (onset of symptoms) for a maximum of 21 days from ictus (or sooner if discharged from neurosurgical centre).</description>
    <arm_group_label>IL-1Ra twice daily</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IL-1Ra Placebo</intervention_name>
    <description>Doses to be administered subcutaneously (SC) twice daily (12 hourly) starting within 72 hours of ictus (onset of symptoms) for a maximum of 21 days from ictus (or sooner if discharged from neurosurgical centre).</description>
    <arm_group_label>Placebo twice daily</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with CT positive spontaneous SAH admitted to a participating neurosurgical&#xD;
             centre where written informed consent can be obtained and study drug can be&#xD;
             administered within 72 hours of ictus.&#xD;
&#xD;
          2. No concomitant health problems that, in the opinion of the PI or designee, would&#xD;
             interfere with participation, administration of study drug or assessment of outcomes&#xD;
             including safety.&#xD;
&#xD;
          3. Willing and able to give informed consent or consent available from a patient&#xD;
             representative for trial inclusion including agreement in principle to receive study&#xD;
             drug and undergo all study assessments.&#xD;
&#xD;
          4. Male or female aged 18 years or above.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unconfirmed or uncertain diagnosis of spontaneous SAH.&#xD;
&#xD;
          2. Known active tuberculosis or active hepatitis.&#xD;
&#xD;
          3. Known active malignancy.&#xD;
&#xD;
          4. Known Still's Disease&#xD;
&#xD;
          5. Neutropenia (ANC &lt;1.5 x 109/L ).&#xD;
&#xD;
          6. Abnormal renal function (creatinine clearance or estimated Glomerular Filtration Rate&#xD;
             (eGFR) &lt; 30 ml/minute) documented in the last 3 months prior to this SAH.&#xD;
&#xD;
          7. Live vaccinations within the last 10 days of this SAH.&#xD;
&#xD;
          8. Previous or concurrent treatment with IL-1Ra known at the time of trial entry or&#xD;
             previous participation in this trial.&#xD;
&#xD;
          9. Current treatment with TNF antagonists.&#xD;
&#xD;
         10. Known to have participated in a clinical trial of an investigational agent or device&#xD;
             in the 30 days prior to ictus.&#xD;
&#xD;
         11. Known to have participated in a clinical trial of an investigational agent or device&#xD;
             within 5 half-lives (of the previous agent or device) prior to ictus.&#xD;
&#xD;
         12. Known to be pregnant or breast feeding or inability to reliably confirm that the&#xD;
             patient is not pregnant&#xD;
&#xD;
         13. Clinically significant serious concurrent medical condition, pre morbid illnesses, or&#xD;
             concurrent serious infection, at the PI's (or designee's) discretion, which could&#xD;
             affect the safety or tolerability of the intervention.&#xD;
&#xD;
         14. Known allergy to IL-1Ra or any of the excipients listed in the drug SmPC&#xD;
&#xD;
         15. Known allergy to other products that are produced by DNA technology using the&#xD;
             micro-organism E. coli (e.g. E.coli derived protein).&#xD;
&#xD;
         16. Current treatment with IL-6 or IL-1 inhibitors or drugs affecting the IL-1 axis.&#xD;
&#xD;
         17. History of DRESS syndrome.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew King</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Manchester</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kayle-Anne Sands, BSc, MSc</last_name>
    <phone>0161 306 3196</phone>
    <email>scil@manchester.ac.uk</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Andrew King</last_name>
    <email>andrew.king@manchester.ac.uk</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Derriford Hospital</name>
      <address>
        <city>Plymouth</city>
        <state>Devon</state>
        <zip>PL6 8DH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter Whitfield</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Hallamshire Hospital</name>
      <address>
        <city>Sheffield</city>
        <state>South Yorkshire</state>
        <zip>S10 2JF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yahia Al-Tamimi</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Hospital of Wales</name>
      <address>
        <city>Cardiff</city>
        <state>Wales</state>
        <zip>CF14 4XW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>James Galea</last_name>
      <email>james.galea@manchester.ac.uk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Leeds General Infirmary</name>
      <address>
        <city>Leeds</city>
        <state>Yorkshire</state>
        <zip>LS1 3EX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ian Anderson</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Sussex County Hospital</name>
      <address>
        <city>Brighton</city>
        <zip>BN2 5BE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Benjamin Fisher</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Southmead Hospital</name>
      <address>
        <city>Bristol</city>
        <zip>BS10 5NB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mario Teo</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Addenbrookes Hospital</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Matthew Guilfoyle</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Walton Centre</name>
      <address>
        <city>Liverpool</city>
        <zip>L9 7LJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrew Brodbelt</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal London Hospital</name>
      <address>
        <city>London</city>
        <zip>E1 1FR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christopher Uff</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>St George's Hospital</name>
      <address>
        <city>London</city>
        <zip>SW17 0QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Marios Papadopoulos</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Charing Cross Hospital</name>
      <address>
        <city>London</city>
        <zip>W6 8RF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Arthur Dalton</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Hospital for Neurology and Neurosurgery, Queen Square</name>
      <address>
        <city>London</city>
        <zip>WC1N 3BG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ahmed Toma</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Northern Care Alliance NHS Foundation Trust</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Hiren Patel, MBBS FRCS</last_name>
      <email>hiren.patel@nca.nhs.uk</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Queens Medical Centre</name>
      <address>
        <city>Nottingham</city>
        <zip>NG7 2UH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Surajit Basu</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Preston Hospital</name>
      <address>
        <city>Preston</city>
        <zip>PR2 9HT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrew Alalade</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Southampton General Hospital</name>
      <address>
        <city>Southampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Diederik Bulters</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Stoke University Hospital</name>
      <address>
        <city>Stoke-on-Trent</city>
        <zip>ST4 6QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Nikolaos Tzerakis</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>August 9, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>August 9, 2023</last_update_submitted>
  <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Manchester</investigator_affiliation>
    <investigator_full_name>Kayle-Anne Sands</investigator_full_name>
    <investigator_title>Clinical Trials Manager</investigator_title>
  </responsible_party>
  <keyword>Aneurysmal</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Subarachnoid Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Interleukin 1 Receptor Antagonist Protein</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03249207
org study id: R121178
nct id: NCT03249207
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This phase III trial will establish whether IL-1Ra, with sub-cutaneous (SC) administration
      twice daily for up to 21 days post aneurysmal subarachnoid haemorrhage (aSAH), improves
      clinical outcome as measured by ordinal shift in mRS at 6 months.

      Patients with SAH transferred to a neurosurgical centre will be identified and approached for
      study participation. Following consent, patients will be randomised to receive either IL-1Ra
      or placebo for a maximum of 21 days from onset of symptoms. Patients who are found to be
      non-aneurysmal following randomisation will be withdrawn from the study treatment. Blood
      samples for plasma IL-6 will be obtained prior to randomisation and at day 3-5 post
      randomisation for IL-6 & IL-1 measurement. Safety will be measured at 30 days post
      randomisation and outcome assessed at 6 months post randomisation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Ordinal shift in modified Rankin Score (mRS)
time frame: 6 months post randomisation
measure: Measurement of mood using HADS
time frame: 6 months post randomisation
measure: Measurement of fatigue using Fatigue score
time frame: 6 months post randomisation
measure: Measurement of quality of life using EQ-5D-5L score
time frame: 6 months post randomisation
arm group label: IL-1Ra twice daily
arm group type: Active Comparator
arm group label: Placebo twice daily
arm group type: Placebo Comparator
intervention type: Drug
intervention name: IL-1Ra
description: Doses to be administered subcutaneously (SC) twice daily (12 hourly) starting within 72 hours of ictus (onset of symptoms) for a maximum of 21 days from ictus (or sooner if discharged from neurosurgical centre).
arm group label: IL-1Ra twice daily
intervention type: Drug
intervention name: IL-1Ra Placebo
description: Doses to be administered subcutaneously (SC) twice daily (12 hourly) starting within 72 hours of ictus (onset of symptoms) for a maximum of 21 days from ictus (or sooner if discharged from neurosurgical centre).
arm group label: Placebo twice daily
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew King
role: Principal Investigator
affiliation: University of Manchester
last name: Kayle-Anne Sands, BSc, MSc
phone: 0161 306 3196
email: scil@manchester.ac.uk
last name: Andrew King
email: andrew.king@manchester.ac.uk
facility: 
status: Recruiting
contact: 
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status: Recruiting
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status: Recruiting
contact: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: University of Manchester
investigator full name: Kayle-Anne Sands
investigator title: Clinical Trials Manager
mesh term: Subarachnoid Hemorrhage
mesh term: Hemorrhage
mesh term: Interleukin 1 Receptor Antagonist Protein