Clinical trial NCT05955326: Study to Assess the Safety and Efficacy of Sovateltide in Patients With Acute Cerebral Ischemic Stroke
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Acute Cerebral Ischemia
Keywords: Stroke
Endothelin
Endothelin B Receptors
Ischemia
IRL 1620
Sovateltide
Neural progenitors
Lead sponsor: Pharmazz, Inc.
Sponsor class: INDUSTRY
First posted: 2023-07-21
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 78
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The Investigational product (IP) is Sovateltide. It is a lyophilized product, available as Sovateltide injection containing 30 μg of Sovateltide (IRL-1620) in a 5.0 mL vial. The investigational product will be provided by Pharmazz India Pvt. Ltd. Three doses of Sovateltide (each dose of 0.3 μg/kg body weight) will be administered as an IV bolus over one minute at 3 ± 1 hours interval on day 1. The dose will be repeated on day 3 and day 6 post-randomization. Sovateltide will be administered as an IV bolus dose over one minute within 24 hours of the stroke onset. All the patients in the Sovateltide group will continue receiving standard treatment. The reference product is Normal Saline therapy. Three doses of Normal Saline (Equal volume) will be administered as an IV bolus over one minute, at an interval of 3 hours ± 1 hour on day 1. The dose will be repeated on day 3 and day 6 post-randomization. All the patients in the Normal Saline group will continue receiving standard treatment.
Primary purpose: TREATMENT

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.

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 4. 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.

Primary outcomes:
measure: The proportion of patients with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 90 days
Secondary outcomes:
measure: The proportion of cerebral ischemic stroke patients with a change in modified Rankin Scale (mRS) score of ≥2
timeFrame: 90 days
measure: The proportion of cerebral ischemic stroke patients with a change in National Institute of Health Stroke Scale (NIHSS) score ≥6
timeFrame: 90 days
measure: The proportion of cerebral ischemic stroke patients with a change in Barthel index (BI) score ≥60
timeFrame: 90 days
measure: Change in National Institute of Health Stroke Scale (NIHSS) score
timeFrame: 90 days
measure: Change in modified Rankin Scale (mRS) score
timeFrame: 90 days
measure: Change in Barthel index (BI) score
timeFrame: 90 days
measure: Change in Quality-of-life as assessed by EuroQol-EQ-5D
timeFrame: 90 days
measure: Change in Stroke-Specific Quality of Life (SSQOL)
timeFrame: 90 days
measure: The proportion of patients with recurrent cerebral ischemic stroke
timeFrame: 90 days
measure: Number of deaths
timeFrame: 90 days
measure: Proportion of patients with radiographic or symptomatic intracerebral hemorrhage (ICH)
timeFrame: 30 hours
Other outcomes:
measure: Compare baseline Alberta Stroke Program Early CT (ASPECT) Score for stroke severity and identify sites of ischemic lesions
timeFrame: 90 days
Locations:
city: Guntur
country: India
facility: Guntur Medical College and Government General Hospital
state: Andhra Pradesh
city: Guntur
country: India
facility: Lalitha Super Specialities Hospital Pvt. Ltd.
state: Andhra Pradesh
city: Amaravati
country: India
facility: Radiant Superspeciality Hospital
state: Maharashtra
city: Kota
country: India
facility: Government Medical College and attached Hospitals
state: Rajasthan
city: Coimbatore
country: India
facility: KG Hospital and Post Graduate Medical Institute
state: Tamil Nadu
city: Jhansi
country: India
facility: Maharani Laxmibai Medical College
state: Uttar Pradesh
Study officials:
affiliation: Pharmazz India
name: Manish Lavhale, Ph.D.
role: STUDY_DIRECTOR
References:
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citation: Ranjan AK, Briyal S, Gulati A. Sovateltide (IRL-1620) activates neuronal differentiation and prevents mitochondrial dysfunction in adult mammalian brains following stroke. Sci Rep. 2020 Jul 29;10(1):12737. doi: 10.1038/s41598-020-69673-w.
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