The Efficacy and Safety of Sofadil for Injection in the Treatment of Acute Ischemic Stroke

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

To evaluate the efficacy and safety of sofadil injection in the treatment of acute ischemic stroke

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: sofadil【Neu2000KW】; Drug: Sofadil; Drug: Sofadil; Other: placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 236
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Dongsheng Fan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The target population is 35-75 years old, regardless of gender;
• within 6h of onset, ischemic stroke of the internal carotid artery system;
• Neurological deficits, including limb weakness, with acute brain injury (NIHSS score) (4-22 points), or NIHSS item 5 upper limb or 6 lower limb score ≥2 points;
• Be able to initiate study treatment within 6 hours of onset of symptoms or within 6 hours of last appearing normal (6 hours after sleep in subjects with ischemic stroke who developed during sleep) and complete post-onset CT examination prior to study treatment;
• Obtain the informed consent signed by the subject or the subject's legal representative;
• MRS score before onset was 0~1;
• Patients with no history of myocardial infarction within 3 months;
• Centerless, liver, kidney and lung dysfunction;
• No hemorrhagic disease within 3 months;
• No blood system diseases.

Exclusion Criteria:

• Any contraindications to CT or MRI (such as metal implants such as pacemaker, claustrophobia, etc
• Stroke caused by posterior circulation ischemia, or TIA;
• Acute intracranial hemorrhage, intracranial tumor, subarachnoid hemorrhage, encephalitis or other non-acute ischemic stroke (onset less than 6 hours), intracranial arteriovenous malformations;
• Patients who plan to undergo endovascular treatment, such as mechanical thrombectomy, stenting or arteriovenous bridging, within 6 hours after onset;
• Pregnant or lactating women. Note: The blood pregnancy test for fertile women before randomization must be negative and appropriate contraception should be used at least 3 weeks before randomization until 7 days after study drug infusion
• A pre-existing medical, neurological or psychiatric disorder that confuses neurological, functional or imaging assessments, such as persistent injury from previous ischemic stroke;
• Patients with malignant tumors or other critical diseases;
• Having a history of epilepsy or having epileptiform symptoms at the onset of stroke;
• Previous history of intracranial hemorrhage;
• Patients with previous hypotension or blood pressure of less than 90/60mmhg measured for 3 consecutive times;
• Patients with severe injuries and surgical history within 3 months;
• People with consciousness disorder can be defined as "NIHSS score Ia ≥2 points";
• Bradycardia with complete atrioventricular block;
• According to the New York heart association (NYHA) grade of cardiac function, cardiac function rating above Ⅱ level, a history of congestive heart failure (CHF).
• Patients with primary liver and kidney diseases, AST or ALT twice as high as the normal upper limit, serum creatinine >2.0 mg/dL or >176.8 mol/L;
• Where the INR is greater than 1.7 or where an oral anticoagulant is currently used, except aspirin, clopidogrel, subcutaneous heparin or Wartamine;
• Patients with bleeding tendency diseases (such as hemophilia), and partial thromboplastin time (PTT) is more than 3 times of the normal upper limit;
• Having a current drug or alcohol problem or experience;
• Has the experience of allergic reaction to the research drugs or drugs with similar chemical structure;
• Participated in other clinical trials or clinical study participants within 3 months before the start of this study;
• The researcher considered it inappropriate to participate in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Group A ：low dose sofadil; 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	Drug: sofadil【Neu2000KW】; 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; Other Names: low dose
EXPERIMENTAL: Group B: Medium dose group; 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	Drug: Sofadil; 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; Other Names: Medium dose; Drug: Sofadil; 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; Other Names: high dose
EXPERIMENTAL: Group C: high dose group; 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	Drug: Sofadil; 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; Other Names: Medium dose; Drug: Sofadil; 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; Other Names: high dose
PLACEBO_COMPARATOR: Group D: placebo group; Saline was administered intravenously	Other: placebo; Saline was administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with a NIHSS score	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	14±2 days of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in NIHSS score	Changes in NIHSS score at 14±2, 30±2, and 90±7 days after treatment compared to baseline	at 14±2, 30±2, and 90±7 days after treatment compared to baseline

Collaborators and Investigators

• Sponsor: Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 1, 2016
• Primary Completion (ACTUAL): January 1, 2018
• Study Completion (ACTUAL): January 1, 2018

Study Registration Dates

• First Submitted: June 28, 2020
• First Submitted That Met QC Criteria: June 30, 2020
• First Posted (ACTUAL): July 1, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 1, 2020
• Last Update Submitted That Met QC Criteria: June 30, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Sofadil; Acute ischemic stroke
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: PUTH2017013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No