A Study to Evaluate the Efficacy and Safety of TF0023 Spray on Subjects With Ischemic Strokes "TF0023"

Recruiting

Phase 2 Results N/A

Trial Description

This is a phase 2, multicenter, randomized, double-blind (within dose), placebo controlled, parallel-group, dose-range finding study to evaluate the efficacy and safety of TF0023 spray versus placebo in functional improvement of patients with ischemic strokes under standard of care.
Objective of the study:
To evaluate the efficacy of TF0023 spray compared with placebo for functional improvement of patients with ischemic strokes measured by the change from baseline in the mRS score for all randomized patients at Week 16 for Part A and Part B, separately.

Detailed Description

This randomized, double-blind (within dose), placebo-controlled, parallel group study will be conducted in 2 parts to evaluate the efficacy and safety of TF0023 spray versus placebo in functional improvement in patients with ischemic strokes. Part A will evaluate the safety and efficacy of TF0023 spray in a higher dose . Efficacy will be assessed by the change in modified Rankin Scale (mRS) score from baseline to Week 16. At Week 16, a blinded interim analysis will be performed to determine if TF0023 shows positive results with a higher proportion of patients in the TF0023 group showing a more favorable outcome compared with the placebo group. If the results are positive, then Part B will be initiated to further evaluate safety and efficacy of TF0023 spray as well as to determine the best dosing regimen for the signs and symptoms and functional improvement of patients with ischemic strokes.
Part A (Proof-of-Concept) In Part A (proof-of-concept), approximately 200 patients who are stable per the NIHSS will be screened as early as 3 days (72 hours) after the onset of stroke symptoms and approximately 75 will be randomized to active or placebo treatment in a 2:1 ratio (TF0023 [50 patients] and placebo [25 patients]).
Each patient enrolled in Group A will receive study treatment in a double-blind manner for 16 weeks starting between 3 and 10 days after the onset of stroke symptoms (Day 1 of the study). Qualified study personnel will instruct the patients and/or caregivers how to apply the study treatment accurately so that patients or caregivers will administer high dose of either TF0023 or placebo twice daily (approximately every 12 hours).
Patients will return to the study site at Weeks 4, 8, 12, and 16 for efficacy and safety assessments. After the Week 16 assessments have been performed, patients will receive active treatment in an open-label manner starting the next day through the end of the study (EOS) at Week 32. That is, patients who were receiving active treatment will continue to receive active treatment, and patients who were receiving placebo will switch to active treatment for the remaining 16 weeks of the study. Patients will receive only one dose of study treatment on the Week 16 visit day. Patients will return to the study site at Week 24 and Week 32 (EOS) for efficacy and safety assessments. An Early Termination visit will occur if the patient is discontinued from the study prematurely. Patients will have a follow-up visit approximately 14 days after the Early Termination visit or the Week 32 (EOS) visit.
An interim analysis will be performed using the data collected through the study up to and including the Week 16 visit. If the analysis of the mRS shows that treatment with TF0023 is positive compared with placebo (mRS score of 0 to 2 indicates functional independence), Part B will start to enroll patients. If the analysis shows that treatment with TF0023 is not positive compared with placebo (mRS score >2), Part B will not enroll any patients.
Treatment group assignment for the Week 16 interim analysis will remain blinded to the Investigator and the patient throughout the duration of the study.
Part B (Dose-Range-Finding) In Part B (dose-range-finding), approximately 400 patients who are stable per the NIHSS will be screened as early as 3 days (72 hours) after the onset of stroke symptoms and approximately 150 will be randomized in a 1:1 ratio to Group B (middle dose of TF0023 or placebo twice daily) or Group C (low dose of TF0023 or placebo twice daily ). Patients will be further randomized in a 2:1 ratio within each treatment group: Group B - TF0023 middle dose bid [50 patients] or placebo [25 patients]) and Group C (TF0023 low dose bid [50 patients] or placebo [25 patients]). The study design in Part B will be the same as used in Part A.
Each patient enrolled in either Group B or Group C will receive study treatment in a double blind manner for 16 weeks starting between 3 and 10 days after the onset of stroke symptoms (Day 1 of the study). Qualified study personnel will instruct the patients and/or caregivers how to apply the study treatment accurately so that patients or caregivers will administer the correct number of sprays/dose of active treatment or placebo twice daily (approximately every 12 hours) depending on the assigned treatment group.
Patients will return to the study site at Weeks 4, 8, 12, and 16 for efficacy and safety assessments. After the Week 16 assessments have been performed, patients will receive active treatment in an open-label manner starting the next day through the EOS at Week 32. That is, patients who were receiving active treatment during the double-blinded period will continue to receive active treatment, and patients who were receiving placebo will switch to active treatment for the remaining 16 weeks of the study. Patients will receive only one dose of study treatment on the Week 16 visit day. Patients will return to the study site at Week 24 and Week 32 (EOS) for efficacy and safety assessments. An Early Termination visit will occur if the patient is discontinued from the study prematurely. Patients will have a follow-up visit approximately 14 days after the Early Termination visit or the Week 32 (EOS) visit.

Conditions

Interventions

  • TF0023 Drug
    Other Names: Active drug
    Intervention Desc: TF0023 is a new Investigational drug as a topical spray as an anti thrombosis drug, indicated for relief of the signs and symptoms and functional improvement of patients with ischemic strokes.
    ARM 1: Kind: Experimental
    Label: 280 mg/day
    Description: 75 patients will be randomized to active or placebo treatment in a 2:1 ratio (TF0023 [50 patients] and placebo [25 patients]). Each patient enrolled in Group A will receive study treatment in a double-blind manner for 16 weeks starting between 5 and 10 days after the onset of stroke symptoms (Day 1 of the study). Each patient or caregiver in Group A will administer the 20 sprays of study treatment as follows: 4 sprays around the neck, 2 sprays to the left shoulder, 2 sprays to the right shoulder, 6 sprays to the chest, 3 sprays to the left leg, and 3 sprays to the right leg.
    ARM 2: Kind: Experimental
    Label: 140 mg/day
    Description: 75 patients will be randomized to active or placebo treatment in a 2:1 ratio (TF0023 [50 patients] and placebo [25 patients]). Each patient enrolled in Group A will receive study treatment in a double-blind manner for 16 weeks starting between 5 and 10 days after the onset of stroke symptoms (Day 1 of the study). Each patient or caregiver in Group B will administer the study treatment as follows: 2 sprays to the front of the neck, 1 spray to the left side of the neck, 1 spray to the right side of the neck, 6 sprays to the chest close to the neck twice daily for a total of 20 sprays (140 mg)/day.
    ARM 3: Kind: Experimental
    Label: 70 mg/day
    Description: 75 patients will be randomized to active or placebo treatment in a 2:1 ratio (TF0023 [50 patients] and placebo [25 patients]). Each patient enrolled in Group A will receive study treatment in a double-blind manner for 16 weeks starting between 5 and 10 days after the onset of stroke symptoms (Day 1 of the study). Each patient or caregiver in Group C will administer the study treatment as follows: 1 spray to the front of the neck, 1 spray to the left side of the neck, 1 spray to the right side of the neck, 2 sprays to the chest twice daily for a total of 10 sprays (70 mg/day).
    ARM 4: Kind: Experimental
    Label: 40 sprays/day
    Description: 75 patients will be randomized to active or placebo treatment in a 2:1 ratio (TF0023 [50 patients] and placebo [25 patients]). Each patient enrolled in Group A will receive study treatment in a double-blind manner for 16 weeks starting between 5 and 10 days after the onset of stroke symptoms (Day 1 of the study). Each patient or caregiver in Group A will administer the 20 sprays of study treatment as follows: 4 sprays around the neck, 2 sprays to the left shoulder, 2 sprays to the right shoulder, 6 sprays to the chest, 3 sprays to the left leg, and 3 sprays to the right leg.
    ARM 5: Kind: Experimental
    Label: 20 sprays/day
    Description: 75 patients will be randomized to active or placebo treatment in a 2:1 ratio (TF0023 [50 patients] and placebo [25 patients]). Each patient enrolled in Group A will receive study treatment in a double-blind manner for 16 weeks starting between 5 and 10 days after the onset of stroke symptoms (Day 1 of the study). Each patient or caregiver in Group B will administer the study treatment as follows: 2 sprays to the front of the neck, 1 spray to the left side of the neck, 1 spray to the right side of the neck, 6 sprays to the chest close to the neck twice daily for a total of 20 sprays/day.
    ARM 6: Kind: Experimental
    Label: 10 sprays/day
    Description: 75 patients will be randomized to active or placebo treatment in a 2:1 ratio (TF0023 [50 patients] and placebo [25 patients]). Each patient enrolled in Group A will receive study treatment in a double-blind manner for 16 weeks starting between 5 and 10 days after the onset of stroke symptoms (Day 1 of the study). Each patient or caregiver in Group C will administer the study treatment as follows: 1 spray to the front of the neck, 1 spray to the left side of the neck, 1 spray to the right side of the neck, 2 sprays to the chest twice daily for a total of 10 sprays .
    ARM 7: Kind: Experimental
    Label: High dose
    Description: 75 patients will be randomized to active or placebo treatment in a 2:1 ratio (TF0023 [50 patients] and placebo [25 patients]). Each patient enrolled in Group A will receive study treatment in a double-blind manner for 16 weeks starting between 3 and 10 days after the onset of stroke symptoms (Day 1 of the study).
    ARM 8: Kind: Experimental
    Label: Middle dose
    Description: 75 patients will be randomized to active or placebo treatment in a 2:1 ratio (TF0023 [50 patients] and placebo [25 patients]). Each patient enrolled in Group A will receive study treatment in a double-blind manner for 16 weeks starting between 3 and 10 days after the onset of stroke symptoms (Day 1 of the study).
    ARM 9: Kind: Experimental
    Label: Low dose
    Description: 75 patients will be randomized to active or placebo treatment in a 2:1 ratio (TF0023 [50 patients] and placebo [25 patients]). Each patient enrolled in Group A will receive study treatment in a double-blind manner for 16 weeks starting between 3 and 10 days after the onset of stroke symptoms (Day 1 of the study).

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator)
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary The primary efficacy endpoint is the change from baseline in the mRS score for all randomized patients at Week 16 in Part A and Part B. 16 weeks of treatment Yes
Secondary Death due to any cause after signing the informed consent form through Week 16 and Week 32. 16 and 32 weeks of treatment Yes
Secondary Recurrent stroke after signing the informed consent form through Week 16 and Week 32. 16 and 32 weeks of treatment Yes
Secondary NIHSS score changes after signing the informed consent form through Week 16 and Week 32. 0, 16 and 32 weeks of treatment Yes
Secondary Barthel Index (BI) changes after signing the informed consent form through Week 16 and Week 32. 0, 16 and 32 weeks of treatment Yes
Secondary Extended Glasgow Outcome Scale (GOS-E) changes after signing the informed consent form through Week 16 and Week 32. 0, 16 and 32 weeks of treatment Yes
Secondary Shortening the time for performing the timed Trail-Making Tests 16 and 32 weeks of treatment Yes
Secondary Volume of new fluid attenuation inversion recovery (FLAIR) lesions by DTI-MRI 16 and 32 weeks of treatment Yes
Secondary Blood flow and improvement of atherosclerosis in neck arteries by Ultrasonography after signing the informed consent form through Week 16 and Week 32. 16 and 32 weeks of treatment Yes
Secondary Daily activities changes after signing the informed consent form through Week 16 and Week 32. 0, 16 and 32 weeks of treatment Yes
Secondary Sleeping condition changes after signing the informed consent form through Week 16 and Week 32. 0, 16 and 32 weeks of treatment Yes
Secondary Total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and very low density lipoprotein cholesterol (VLDL C) changes 0, 16 and 32 weeks of treatment Yes
Secondary Blood pressure changes after signing the informed consent form through Week 16 and Week 32. 0, 16 and 32 weeks of treatment Yes
Secondary To access hemoglobin A1C (HbA1C) changes after signing the informed consent form through Week 16 and Week 32. 0, 16 and 32 weeks of treatment Yes
Secondary To access patient's assessment of disease status 0, 16 and 32 weeks of treatment Yes
Secondary To access investigator's assessment of disease status 0, 16 and 32 weeks of treatment Yes
Secondary To access patient's assessment of response to therapy 16 and 32 weeks of treatment Yes
Secondary To access investigator's assessment of response to therapy 16 and 32 weeks of treatment Yes
Secondary Blood flow in neck arteries by Ultrasonography after signing the informed consent form through Week 16 and Week 32. 16 and 32 weeks of treatment Yes
Secondary Improvement of atherosclerosis in neck arteries by Ultrasonography after signing the informed consent form through Week 16 and Week 32. 16 and 32 weeks of treatment Yes

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