A Prospective, Multicentric, Randomized, Double-blind, Parallel, Phase IV Study to Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke
Overview
- Phase
- Phase 4
- Intervention
- Sovateltide
- Conditions
- Acute Cerebral Ischemia
- Sponsor
- Pharmazz, Inc.
- Enrollment
- 160
- Locations
- 6
- Primary Endpoint
- The proportion of patients with adverse events (AEs) and serious adverse events (SAEs)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a prospective, multicenter, randomized, double-blind, parallel, phase IV study designed to evaluate the safety and efficacy of sovateltide (PMZ-1620, IRL-1620) as a potential treatment for cerebral ischemic stroke.
Detailed Description
The presence of stem cells in the brain that become active after brain injury is an interesting aspect of regeneration and repair after stroke. The intravenous administration of sovateltide (TYVALZI™, IRL 1620) enhances the activity of neuronal progenitor cells and angiogenesis in the brain. This promotes the formation of new mature neurons and blood vessels, aiding in the repair process. Additionally, sovateltide exhibits anti-apoptotic activity, preventing cell death, and it can increase cerebral blood flow when administered after ischemia. These properties make sovateltide a promising candidate for promoting brain repair and facilitating recovery following acute ischemic stroke. The study aims to evaluate the safety and efficacy of sovateltide in 160 patients with acute cerebral ischemic stroke. Sovateltide will be administered intravenously in addition to standard treatment. The patients will be divided into two groups, with 80 patients in each. Group 1 will receive sovateltide along with standard treatment, while Group 2 will receive normal saline along with standard treatment. The study will span approximately 18 months, with a patient enrollment period of around 15 months. Each patient will be followed for a total of 3 months, with three study visits during that period. The study will adhere to ethical guidelines and obtain informed consent from patients or their legally acceptable representatives. Efficacy analysis will be performed using statistical tests to compare outcomes between the groups, including NIHSS (National Institutes of Health Stroke Scale), mRS (Modified Rankin Scale), and BI (Barthel index) scores. Safety analysis will involve monitoring and categorizing adverse events (AEs) and treatment-emergent adverse events (TEAEs) using standardized medical terminology. Adverse events will be evaluated based on their relationship to the study drug, seriousness, severity, actions taken, and outcomes. Clinical laboratory parameters, vital signs, and physical examinations will also be assessed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult males or females aged 18 years through 78 years (have not had their 79th birthday)
- •Patient or Legally Acceptable Representative (LAR) willing to give informed consent before study procedure.
- •Stroke is ischemic in origin and radiologically confirmed Computed Tomography (CT) scan or diagnostic magnetic resonance imaging (MRI) before enrolment. No hemorrhage as proved by cerebral CT/MRI scan.
- •Cerebral ischemic stroke patients presenting within 24 hours after onset of symptoms with mRS score of 3-4 (pre-stroke mRS score of 0 or 1) and NIHSS score \>5 (NIHSS Level of Consciousness (1A) score must be \< 2). This includes cerebral ischemic stroke patients who completely recovered from earlier episodes before having a new or fresh stroke.
- •The patient is \<24 hours from the time of stroke onset when the first dose of Sovateltide therapy is administered. Time of onset is when symptoms began; for stroke that occurred during sleep, time of onset is when the patient was last seen or was self-reported to be normal.
- •Reasonable expectation of availability to receive the full Sovateltide course of therapy and to be available for subsequent follow-up visits.
Exclusion Criteria
- •Patients receiving endovascular therapy or is a candidate for any surgical intervention for the treatment of stroke, which may include but not limited to endovascular techniques.
- •Patients classified as comatose are defined as a patient who requires repeated stimulation to attend or is obtunded and requires strong or painful stimulation to make movements (NIHSS Level of Consciousness (1A) score ≥ 2).
- •Evidence of intracranial hemorrhage (intracerebral hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, epidural hemorrhage, an acute or chronic subdural hematoma on the baseline CT or MRI scan
- •Known pregnancy.
- •Confounding pre-existing neurological or psychiatric disease.
- •Concurrent participation in any other therapeutic clinical trial.
- •Evidence of any other major life-threatening or serious medical condition that would prevent completion of the study protocol, impair the assessment of outcome, or in which Sovateltide therapy would be contraindicated or might cause harm to the patient.
Arms & Interventions
Sovateltide (Tyvalzi™) + Standard treatment
A total of 80 patients will be enrolled in the experimental arm. Three doses of sovateltide (each dose of 0.3 μg/kg body weight) will be given as an IV bolus in each patient (randomly assigned to this group) over one minute at an interval of 3 ± 1 hours on day 1, day 3, and day 6 (total dose/day: 0.9 μg/kg body weight). All patients will receive standard stroke treatment as provided by the specific hospital setup. Patients will be closely monitored for the qualifying stroke, followed for 3 months, and assessed for safety and efficacy parameters. Efforts will be made to administer the drug at the same time on days 1, 3, and 6.
Intervention: Sovateltide
Normal Saline (Dose: Equal volume) + Standard Treatment
A total of 80 patients will be enrolled in this arm. Three doses of an equal volume of normal saline will be administered as an IV bolus in each patient (randomly assigned to this group) over one minute at an interval of 3 ± 1 hours on day 1, day 3, and day 6. All patients will receive standard stroke treatment as provided by the specific hospital setup. Patients will be closely monitored for the qualifying stroke, followed for 3 months, and assessed for safety and efficacy parameters. Efforts will be made to administer the drug at the same time on days 1, 3, and 6.
Intervention: Normal Saline
Outcomes
Primary Outcomes
The proportion of patients with adverse events (AEs) and serious adverse events (SAEs)
Time Frame: 90 days
Any unfavorable sign, symptom, or disease that occurs while using sovateltide will be reported as an adverse event (AE), including the worsening of pre-existing medical conditions. A severe medical occurrence, such as death, life-threatening situations, hospitalization, significant disability, or congenital anomalies will be reported as a serious adverse event (SAE). All AEs will be collected on CRFs from when the patient signs the informed consent form (ICF) until the study exit. Any SAE that is ongoing at the time the patient exits the study must be followed until the event is resolved or there is a satisfactory explanation that meets one of the following outcomes: 1. Resolved (With sequelae or without sequelae). 2. Death and 3. Unknown (Despite adequate follow-up).
Secondary Outcomes
- The proportion of cerebral ischemic stroke patients with a change in National Institute of Health Stroke Scale (NIHSS) score ≥6(90 days)
- The proportion of cerebral ischemic stroke patients with a change in Barthel index (BI) score ≥60(90 days)
- Change in National Institute of Health Stroke Scale (NIHSS) score(90 days)
- Change in modified Rankin Scale (mRS) score(90 days)
- Change in Barthel index (BI) score(90 days)
- The proportion of cerebral ischemic stroke patients with a change in modified Rankin Scale (mRS) score of ≥2(90 days)
- Change in Quality-of-life as assessed by EuroQol-EQ-5D(90 days)
- Change in Stroke-Specific Quality of Life (SSQOL)(90 days)
- The proportion of patients with recurrent cerebral ischemic stroke(90 days)
- Number of deaths(90 days)
- Proportion of patients with radiographic or symptomatic intracerebral hemorrhage (ICH)(30 hours)