PMZ-1620 (Sovateltide) in Patients of Acute Spinal Cord Injury

Acute Spinal Cord Injury Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04054414
• Other study ID #: PMZ-1620/CLINICAL-2.3/2017
• Secondary ID: CTRI/2018/12/016
• Status: Recruiting
• Phase: Phase 2
• Start date: January 10, 2019
• Est. completion date: July 2024

Study information

• Verified date: July 2023
• Source: Pharmazz, Inc.
• Contact: Manish S Lavhale
• Phone: +91 9873847397
• Email: manish.lavhale[@]pharmazz.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: July 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Spinal Cord Injury
• Spinal Cord Injuries
• Wounds and Injuries

Intervention

Drug:
• Normal Saline along with standard treatment
The arm is for active comparison for PMZ-1620 (sovateltide), an endothelin-B receptor agonist. PMZ-1620 has the potential to be a first-in-class neuronal progenitor cell therapeutics that is likely to promote quicker recovery and improve neurological outcome in cerebral ischemic stroke patients. Normal saline (vehicle) with standard treatment will be provided.
• PMZ-1620 along with standard treatment
PMZ-1620 (sovateltide) is an endothelin-B receptor agonist. PMZ-1620 has the potential to be a first-in-class neuronal progenitor cell therapeutics that is likely to promote quicker recovery and improve neurological outcome in cerebral ischemic stroke patients.

Locations

Country	Name	City	State
India	KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre	Belgaum
India	Institute of Postgraduate Medical Education & Research and SSKM Hospital	Kolkata
India	King George's Medical University	Lucknow
India	Rahate Surgical Hospital & ICU	Nagpur
India	Indian Spinal Injury Centre	New Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Pharmazz, Inc.

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of PMZ-1620 related adverse events	The primary objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.	90 days
Primary	Number of patients not receiving full treatment	Tolerability will be determined by the number of patients that do not receive all the 9 doses of PMZ-1620.	90 days
Secondary	Changes in clinical progression of International Standards for Neurological Classification of spinal cord injury (ISNCSCI)	Statistically relevant changes in clinical progression of ASCI as measured by ISNCSCI scoring at one, two and three months after treatment. The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) or more commonly referred to as the ASIA Impairment Scale (AIS), is a universal classification tool for Spinal Cord Injury based on a standardized sensory and motor assessment. Ranges from A to E where A = Complete and no sensory or motor function is preserved and E = Normal sensory and motor functions	90 days
Secondary	Changes in walking index for spinal cord injury (WISCI) score	Statistically relevant changes in WISCI Score at one, two and three months after treatment. This test assesses the amount of physical assistance needed, as well as devices required, for walking following paralysis that results from SCI. It rank orders the ability of a person to walk 10 meter after a spinal cord injury from most to least severe impairment. A score from 0 to 20 is assigned, level 0: patient is unable to stand and/or participate in walking and level 20 patient ambulates with no devices, with brace and no assistance.	90 days
Secondary	Changes in Spinal Cord Independence Measure (SCIM) score	Statistically relevant changes in SCIM score at one, two and three months after treatment. Spinal Cord Independence Measure (SCIM) scale is used to measure the disability to specifically address the ability of SCI patients to perform basic activities of daily living independently. The SCIM scores range from 0 to 100 where where a score of 0 defines total dependence and a score of 100 is indicative of complete independence.	90 days
Secondary	Changes in MRI/CT	Changes in MRI/CT, before (baseline) and three months after treatment. Radiological evidence of transaction of spinal cord will be recorded by CT or MRI scan. In addition, edema, contusion, extent of spinal cord damage will be recorded.	90 days
Secondary	Changes in electromyography (EMG)	Changes in EMG, before (baseline) and three months after treatment. Changes in nerve conduction parameters are recorded from the peroneal, tibial, and sural nerves. The presence of spontaneous activity (SA), including fibrillation and positive sharp waves are recorded in muscle groups vastus medialis, iliopsoas, tibialis anterior, medial gastrocnemius, and lumbar paraspinals. A decrease in nerve conduction parameters are indicative to greater severity. A high degree of abnormal SA on electromyographic testing represents the presence of muscle membrane instability.	90 days