Status and phase
Conditions
Treatments
About
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.
Full 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 In Part A , 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 60 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. 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.
Part B In Part B, 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 60 days after the onset of stroke symptoms (Day 1 of the study).
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 have a follow-up visit approximately 14 days after the Early Termination visit or the Week 32 (EOS) visit.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Exclusion criteria
Pregnant or lactating female.
Any condition, including any significant medical or neuropsychiatric condition, including the presence of laboratory abnormalities, which in the judgment of the investigator places the patient at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study including, but not limited to:
History of bacteremia or other serious bacterial or fungal infection requiring treatment with intravenous antibiotics within 84 days (12 weeks) prior to treatment with study therapy other than a treated urinary tract infection.
Known infection with human immunodeficiency virus (HIV).
Seropositive for hepatitis C or hepatitis B.
Known history of seizures.
Evidence of cerebral hemorrhage within the last 6 months or recent intracerebral hematomas detected by brain CT or MRI.
Hypertension with systolic blood pressure (SBP) >185 mmHg or diastolic blood pressure (DBP) >120 mmHG (mean of 3 consecutive arm cuff readings over 20 to 30 minutes).
High clinical suspicion of septic embolus.
History of major trauma at time of stroke.
History of malignancy within 5 years except basal cell or squamous cell carcinoma of the skin or remote history of cancer now considered cured or positive Pap smear with subsequent negative follow up.
Known allergy to non-steroidal anti-inflammatory drugs (NSAIDs).
Known allergy to both gadolinium and iodine based contrast agents for MRI preventing the ability to conduct either one of these procedures.
Patient has received an investigational agent within 90 days or 5 half-lives, whichever is longer, prior to treatment with study therapy or planned participation in another therapeutic trial prior to the completion of this study.
Patients with very light neurological symptoms (NIHSS score of <3) or with rapidly improving symptoms before the start of treatment.
Patients with serious neurological disorders (NIHSS score ≥22) or serious consciousness disorders before the start of treatment.
Patients with functional disorders (mRS score >2) before onset of the stroke.
Patients who have been administered drugs that are not allowed to be administered concomitantly with any anti-thrombotic agents after onset of the stroke.
Patients who are forbidden to undergo DTI-MRI.
Patients with symptoms suggesting subarachnoid hemorrhage (SAH).
Patients with hemorrhage (gastrointestinal hemorrhage, urinary hemorrhage, retroperitoneal hemorrhage, or hemoptysis).
Patients who have been administered oral anticoagulants with values of the international normalized ratio (INR) of prothrombin time (PT-INR) >1.7.
Patients who have a history of intracranial hemorrhage, or who have a disease considered to increase the risk of intracranial hemorrhage such as an intracranial tumor, cerebral aneurysm, or intracranial arteriovenous malformation, etc.
Patients who were operated on or injured their head or spinal cord within 3 months before onset of the stroke.
Patients who have a history of gastrointestinal or urinary tract hemorrhage within 21 days before onset of the stroke.
Patients who had a major surgery or serious trauma (except for head or spinal cord trauma) within 14 days before onset of the stroke.
Patients who had an organ biopsy, arterial puncture, or lumbar puncture within 14 days before the onset of the stroke.
Patients with severe hepatic dysfunction or severe renal dysfunction.
Patients with acute pancreatitis.
Patients with concurrent infectious endocarditis, moyamoya disease (Willis circle occlusion syndrome), aortic dissection, or neck trauma, etc.
Patients judged to be difficult in monitoring for 4 to 7 months by their physician.
In addition to the above exclusion criteria, patients judged to be inadequate to participate in this study by their physician.
Primary purpose
Allocation
Interventional model
Masking
225 participants in 3 patient groups
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal