<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/NCT04453800</url>
  </required_header>
  <id_info>
    <org_study_id>PUTH2017013</org_study_id>
    <nct_id>NCT04453800</nct_id>
  </id_info>
  <brief_title>The Efficacy and Safety of Sofadil for Injection in the Treatment of Acute Ischemic Stroke</brief_title>
  <official_title>A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Study to Evaluate the Efficacy and Safety of Sofadil for Injection in the Treatment of Acute Ischemic Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Peking University Third Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Peking University Third Hospital</source>
  <oversight_info>
    <has_dmc>No</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>
      To evaluate the efficacy and safety of sofadil injection in the treatment of acute ischemic&#xD;
      stroke&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The limited therapeutic time window for neuroprotection has prevented all clinical trials&#xD;
      using NMDA receptor antagonists in subjects with ischemic stroke from showing efficacy. In&#xD;
      animal models of ischemic stroke, antioxidants showed a longer neuroprotective time window&#xD;
      than NMDA receptor antagonists, and also showed therapeutic potential in clinical trials in&#xD;
      subjects with ischemic stroke. Sophadil showed good neuroprotective effects against NMDA and&#xD;
      free-radical mediated cell death, NR2B-selectivity, moderate NMDA receptor antagonism, and&#xD;
      effective cellular osmotic antioxidant activity even at nanoscale molarity. Non-clinical and&#xD;
      phase I human clinical studies have shown that Sofadil is helpful in treating ischemic stroke&#xD;
      subjects with better efficacy and therapeutic time windows. So we designed the clinical trial&#xD;
      to evaluate the efficacy and safety of sofadil injection in the treatment of acute ischemic&#xD;
      stroke&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2016</start_date>
  <completion_date type="Actual">January 1, 2018</completion_date>
  <primary_completion_date type="Actual">January 1, 2018</primary_completion_date>
  <phase>Phase 2</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>
    <masking_description>This study will be conducted in a double-blind form. The clinical research team participating in the study will be divided into two groups: blind and non-blind members, strictly ensuring that researchers and subjects are blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of subjects with a NIHSS score</measure>
    <time_frame>14±2 days of treatment</time_frame>
    <description>Proportion of subjects with a NIHSS score of 0 ~ 1 or 4 or more points less than baseline NIHSS at 14±2 days of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in NIHSS score</measure>
    <time_frame>at 14±2, 30±2, and 90±7 days after treatment compared to baseline</time_frame>
    <description>Changes in NIHSS score at 14±2, 30±2, and 90±7 days after treatment compared to baseline</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">236</enrollment>
  <condition>Acute Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>Group A ：low dose sofadil</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>500mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 250mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B: Medium dose group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>750mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 500mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C: high dose group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1500mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 500mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group D: placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline was administered intravenously</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>sofadil【Neu2000KW】</intervention_name>
    <description>500mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 250mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours</description>
    <arm_group_label>Group A ：low dose sofadil</arm_group_label>
    <other_name>low dose</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sofadil</intervention_name>
    <description>750mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 500mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours</description>
    <arm_group_label>Group B: Medium dose group</arm_group_label>
    <other_name>Medium dose</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sofadil</intervention_name>
    <description>1500mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 500mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours</description>
    <arm_group_label>Group C: high dose group</arm_group_label>
    <other_name>high dose</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>Saline was administered intravenously</description>
    <arm_group_label>Group D: placebo group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The target population is 35-75 years old, regardless of gender;&#xD;
&#xD;
          -  within 6h of onset, ischemic stroke of the internal carotid artery system;&#xD;
&#xD;
          -  Neurological deficits, including limb weakness, with acute brain injury (NIHSS score)&#xD;
             (4-22 points), or NIHSS item 5 upper limb or 6 lower limb score ≥2 points;&#xD;
&#xD;
          -  Be able to initiate study treatment within 6 hours of onset of symptoms or within 6&#xD;
             hours of last appearing normal (6 hours after sleep in subjects with ischemic stroke&#xD;
             who developed during sleep) and complete post-onset CT examination prior to study&#xD;
             treatment;&#xD;
&#xD;
          -  Obtain the informed consent signed by the subject or the subject's legal&#xD;
             representative;&#xD;
&#xD;
          -  MRS score before onset was 0~1;&#xD;
&#xD;
          -  Patients with no history of myocardial infarction within 3 months;&#xD;
&#xD;
          -  Centerless, liver, kidney and lung dysfunction;&#xD;
&#xD;
          -  No hemorrhagic disease within 3 months;&#xD;
&#xD;
          -  No blood system diseases.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any contraindications to CT or MRI (such as metal implants such as pacemaker,&#xD;
             claustrophobia, etc&#xD;
&#xD;
          -  Stroke caused by posterior circulation ischemia, or TIA;&#xD;
&#xD;
          -  Acute intracranial hemorrhage, intracranial tumor, subarachnoid hemorrhage,&#xD;
             encephalitis or other non-acute ischemic stroke (onset less than 6 hours),&#xD;
             intracranial arteriovenous malformations;&#xD;
&#xD;
          -  Patients who plan to undergo endovascular treatment, such as mechanical thrombectomy,&#xD;
             stenting or arteriovenous bridging, within 6 hours after onset;&#xD;
&#xD;
          -  Pregnant or lactating women. Note: The blood pregnancy test for fertile women before&#xD;
             randomization must be negative and appropriate contraception should be used at least 3&#xD;
             weeks before randomization until 7 days after study drug infusion&#xD;
&#xD;
          -  A pre-existing medical, neurological or psychiatric disorder that confuses&#xD;
             neurological, functional or imaging assessments, such as persistent injury from&#xD;
             previous ischemic stroke;&#xD;
&#xD;
          -  Patients with malignant tumors or other critical diseases;&#xD;
&#xD;
          -  Having a history of epilepsy or having epileptiform symptoms at the onset of stroke;&#xD;
&#xD;
          -  Previous history of intracranial hemorrhage;&#xD;
&#xD;
          -  Patients with previous hypotension or blood pressure of less than 90/60mmhg measured&#xD;
             for 3 consecutive times;&#xD;
&#xD;
          -  Patients with severe injuries and surgical history within 3 months;&#xD;
&#xD;
          -  People with consciousness disorder can be defined as &quot;NIHSS score Ia ≥2 points&quot;;&#xD;
&#xD;
          -  Bradycardia with complete atrioventricular block;&#xD;
&#xD;
          -  According to the New York heart association (NYHA) grade of cardiac function, cardiac&#xD;
             function rating above Ⅱ level, a history of congestive heart failure (CHF).&#xD;
&#xD;
          -  Patients with primary liver and kidney diseases, AST or ALT twice as high as the&#xD;
             normal upper limit, serum creatinine &gt;2.0 mg/dL or &gt;176.8 mol/L;&#xD;
&#xD;
          -  Where the INR is greater than 1.7 or where an oral anticoagulant is currently used,&#xD;
             except aspirin, clopidogrel, subcutaneous heparin or Wartamine;&#xD;
&#xD;
          -  Patients with bleeding tendency diseases (such as hemophilia), and partial&#xD;
             thromboplastin time (PTT) is more than 3 times of the normal upper limit;&#xD;
&#xD;
          -  Having a current drug or alcohol problem or experience;&#xD;
&#xD;
          -  Has the experience of allergic reaction to the research drugs or drugs with similar&#xD;
             chemical structure;&#xD;
&#xD;
          -  Participated in other clinical trials or clinical study participants within 3 months&#xD;
             before the start of this study;&#xD;
&#xD;
          -  The researcher considered it inappropriate to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>35 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dongsheng Fan, MD.PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Third Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dongsheng Fan</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100191</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 30, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 1, 2020</study_first_posted>
  <last_update_submitted>June 30, 2020</last_update_submitted>
  <last_update_submitted_qc>June 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Sofadil; Acute ischemic stroke</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Cerebral Infarction</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT04453800
org study id: PUTH2017013
nct id: NCT04453800
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To evaluate the efficacy and safety of sofadil injection in the treatment of acute ischemic
      stroke
The limited therapeutic time window for neuroprotection has prevented all clinical trials
      using NMDA receptor antagonists in subjects with ischemic stroke from showing efficacy. In
      animal models of ischemic stroke, antioxidants showed a longer neuroprotective time window
      than NMDA receptor antagonists, and also showed therapeutic potential in clinical trials in
      subjects with ischemic stroke. Sophadil showed good neuroprotective effects against NMDA and
      free-radical mediated cell death, NR2B-selectivity, moderate NMDA receptor antagonism, and
      effective cellular osmotic antioxidant activity even at nanoscale molarity. Non-clinical and
      phase I human clinical studies have shown that Sofadil is helpful in treating ischemic stroke
      subjects with better efficacy and therapeutic time windows. So we designed the clinical trial
      to evaluate the efficacy and safety of sofadil injection in the treatment of acute ischemic
      stroke
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: This study will be conducted in a double-blind form. The clinical research team participating in the study will be divided into two groups: blind and non-blind members, strictly ensuring that researchers and subjects are blind
measure: Proportion of subjects with a NIHSS score
time frame: 14±2 days of treatment
description: Proportion of subjects with a NIHSS score of 0 ~ 1 or 4 or more points less than baseline NIHSS at 14±2 days of treatment
measure: Changes in NIHSS score
time frame: at 14±2, 30±2, and 90±7 days after treatment compared to baseline
description: Changes in NIHSS score at 14±2, 30±2, and 90±7 days after treatment compared to baseline
arm group label: Group A ：low dose sofadil
arm group type: Experimental
description: 500mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 250mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours
arm group label: Group B: Medium dose group
arm group type: Experimental
description: 750mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 500mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours
arm group label: Group C: high dose group
arm group type: Experimental
description: 1500mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 500mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours
arm group label: Group D: placebo group
arm group type: Placebo Comparator
description: Saline was administered intravenously
intervention type: Drug
intervention name: sofadil【Neu2000KW】
description: 500mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 250mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours
arm group label: Group A ：low dose sofadil
other name: low dose
intervention type: Drug
intervention name: Sofadil
description: 750mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 500mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours
arm group label: Group B: Medium dose group
other name: Medium dose
intervention type: Drug
intervention name: Sofadil
description: 1500mg Intravenous infusion of sofadil starting at 500mg was 500ml，followed by nine intravenous infusions, each 500mg infusion with 250ml sofadil for 5 days, and each interval is 12 hours
arm group label: Group C: high dose group
other name: high dose
intervention type: Other
intervention name: placebo
description: Saline was administered intravenously
arm group label: Group D: placebo group
criteria: 
gender: All
minimum age: 35 Years
maximum age: 75 Years
healthy volunteers: No
last name: Dongsheng Fan, MD.PHD
role: Principal Investigator
affiliation: Peking University Third Hospital
facility: 
country: China
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Cerebral Infarction
mesh term: Ischemia
sharing ipd: No