Clinical trial NCT04054414: PMZ-1620 (Sovateltide) in Patients of Acute Spinal Cord Injury
Official title: A Prospective, Multicentric, Randomized, Double Blind, Saline Controlled Phase II Clinical Study to Compare the Safety and Efficacy of PMZ-1620 Therapy Along With Standard Supportive Care in Patients of Acute Spinal Cord Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Spinal Cord Injury
Keywords: Endothelin
Neurogenesis
Lead sponsor: Pharmazz, Inc.
Sponsor class: INDUSTRY
First posted: 2019-08-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In PMZ group, 3 doses of PMZ-1620, at 0.3 μg/kg body weight will be administered as an intravenous bolus over 1 minute every 3 hours ± 1 hour on day 1, 3, and day 6 (total dose/day: 0.9 µg/kg body weight).

In control group, 3 doses of equal volume of normal saline will be administered as an IV bolus over 1 minutes every 3 hours ± 1 hour on day 1, 3 and day 6 post randomization.

In both treatment groups, subjects will be provided the best available standard of care.
Primary purpose: TREATMENT

Brief summary: This was a prospective, multicentric, randomized, double blind, parallel, saline controlled Phase II clinical study to compare the safety and efficacy of PMZ-1620 (INN: Sovateltide) therapy along with standard supportive care in patients of acute spinal cord injury.

Detailed description: Trauma is projected to be third largest killer in the developing world by 2020, with a large number of these injuries comprising of traumatic spinal cord injury. People with spinal cord injuries (SCI) are two to five times more susceptible to die than people without an injury. More than 80% cases of SCIs occur among young people between the ages of 20 and 45 years and majority of sufferers are male. In developed countries, the incidence of spinal injuries varies from 20 to 50 per million. Every year about 250,000 to 500,000 number of SCI cases are reported.

There are hidden stem cells in the brain, which becomes active following injury to the spinal cord. Intravenous administration of PMZ-1620 (sovateltide) augments the activity of neuronal progenitor cells in the spinal cord to repair the damage by formation of new mature neurons and blood vessels. In addition, PMZ-1620 has anti-apoptotic and anti-oxidant activity.

Sovateltide is an endothelin B (ETB) receptor agonist (previously used names IRL-1620, SPI-1620 and PMZ-1620; International Non-proprietary Name (INN) approved by WHO is sovateltide). Activation of ETB receptors with PMZ-1620 produces neurovascular repair and remodeling or neuroregeneration.

Eligibility criteria: Inclusion Criteria:

1. Adult males or females aged between 18 and 75 years inclusive
2. Able to give consent for participation on their own or through their Legally Acceptable Representative (LAR)
3. Able to cooperate in the completion of a standardized neurological examination by ISNCSCI standards (excludes patients who are on ventilator)
4. ISNCSCI Impairment Scale Grade "B," "C" or "D" based upon first ISNCSCI evaluation after arrival to the hospital is classified as motor or sensory incomplete
5. Willing and able to comply with the study Protocol
6. Women must be of non-childbearing potential or surgically sterile or willing to use adequate birth control; men who are sexually active will also be required to use adequate birth control
7. Able to receive the Investigational Drug within 48 hours of injury
8. Neurological Level of Injury between C5-C8, T1-T12, L1-L5 and S1-S5 based upon first ISNCSCI evaluation after arrival to the hospital
9. Patient with incomplete/partial damage/transaction as shown by CT or MRI scan
10. Patients with any other chronic conditions, who are stable with appropriate treatment

Exclusion Criteria:

1. Previous history related to spinal cord disease
2. Patient on ventilator or requires ventilator
3. Patient with pathological fracture of vertebral column
4. Impairment Scale Grade "A" based upon first ISNCSCI assessment and classified as complete injury
5. One or more upper extremity muscle groups un-testable during baseline ISNCSCI examination
6. Concomitant head injury with a clinically significant abnormality on a head CT (head CT required only for patients suspected to have a brain injury at the discretion of the investigator)
7. Females who are breastfeeding or have a positive urine pregnancy test
8. Body mass index (BMI) of ≥35 kg/m2 at screening
9. Known immunodeficiency, including human immunodeficiency virus, or use of immunosuppressive or cancer chemotherapeutic drugs
10. Patient having rheumatoid arthritis
11. The participant has a clinically significant cardiovascular disorder or an abnormal electrocardiogram (ECG) at the discretion of the investigator
12. Pre-existent neurologic disorder which would preclude accurate evaluation and follow-up (i.e. Alzheimer's disease, Parkinson's disease, any psychiatric disorder with hallucinations/delusions/schizophrenia)
13. Patients who are currently participating in a clinical trial with an investigational drug or investigational device
14. Patients who, in the opinion of the investigator, are otherwise unsuitable for this study

Primary outcomes:
measure: Incidence of PMZ-1620 related adverse events
timeFrame: 90 days
measure: Number of patients not receiving full treatment
timeFrame: 90 days
Secondary outcomes:
measure: Changes in clinical progression of International Standards for Neurological Classification of spinal cord injury (ISNCSCI)
timeFrame: 90 days
measure: Changes in walking index for spinal cord injury (WISCI) score
timeFrame: 90 days
measure: Changes in Spinal Cord Independence Measure (SCIM) score
timeFrame: 90 days
measure: Changes in MRI/CT
timeFrame: 90 days
measure: Changes in electromyography (EMG)
timeFrame: 90 days
Other outcomes:
Locations:
city: Belgaum
country: India
facility: KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
city: Kolkata
country: India
facility: Institute of Postgraduate Medical Education & Research and SSKM Hospital
city: Lucknow
country: India
facility: King George's Medical University
city: Nagpur
country: India
facility: Rahate Surgical Hospital & ICU
city: New Delhi
country: India
facility: Indian Spinal Injury Centre
Study officials:
affiliation: Pharmazz, Inc.
name: Anil Gulati
role: STUDY_CHAIR
References: