Back to resultsPMZ-1620 (Sovateltide) in Patients of Acute Spinal Cord Injury
Primary Purpose
Acute Spinal Cord Injury
Status
Recruiting
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Normal Saline along with standard treatment
PMZ-1620 along with standard treatment
Sponsored by
About this trial
This is an interventional treatment trial for Acute Spinal Cord Injury focused on measuring Endothelin, Neurogenesis
Eligibility Criteria
Inclusion Criteria:
- Adult males or females aged between 18 and 75 years inclusive
- Able to give consent for participation on their own or through their Legally Acceptable Representative (LAR)
- Able to cooperate in the completion of a standardized neurological examination by ISNCSCI standards (excludes patients who are on ventilator)
- 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
- Willing and able to comply with the study Protocol
- 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
- Able to receive the Investigational Drug within 48 hours of injury
- Neurological Level of Injury between C5-C8, T1-T12, L1-L5 and S1-S5 based upon first ISNCSCI evaluation after arrival to the hospital
- Patient with incomplete/partial damage/transaction as shown by CT or MRI scan
- Patients with any other chronic conditions, who are stable with appropriate treatment
Exclusion Criteria:
- Previous history related to spinal cord disease
- Patient on ventilator or requires ventilator
- Patient with pathological fracture of vertebral column
- Impairment Scale Grade "A" based upon first ISNCSCI assessment and classified as complete injury
- One or more upper extremity muscle groups un-testable during baseline ISNCSCI examination
- 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)
- Females who are breastfeeding or have a positive urine pregnancy test
- Body mass index (BMI) of ≥35 kg/m2 at screening
- Known immunodeficiency, including human immunodeficiency virus, or use of immunosuppressive or cancer chemotherapeutic drugs
- Patient having rheumatoid arthritis
- The participant has a clinically significant cardiovascular disorder or an abnormal electrocardiogram (ECG) at the discretion of the investigator
- 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)
- Patients who are currently participating in a clinical trial with an investigational drug or investigational device
- Patients who, in the opinion of the investigator, are otherwise unsuitable for this study
Sites / Locations
- KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
- Institute of Postgraduate Medical Education & Research and SSKM HospitalRecruiting
- King George's Medical UniversityRecruiting
- Rahate Surgical Hospital & ICURecruiting
- Indian Spinal Injury CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Normal Saline
PMZ-1620
Arm Description
Patients will receive the best available standard of care. 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.
Patients will receive the best available standard of care. 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).
Outcomes
Primary Outcome Measures
Incidence of PMZ-1620 related adverse events
The primary objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.
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.
Secondary Outcome Measures
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
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04054414
Brief Title
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
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 10, 2019 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmazz, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Spinal Cord Injury
Keywords
Endothelin, Neurogenesis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Normal Saline
Arm Type
Active Comparator
Arm Description
Patients will receive the best available standard of care. 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.
Arm Title
PMZ-1620
Arm Type
Experimental
Arm Description
Patients will receive the best available standard of care. 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).
Intervention Type
Drug
Intervention Name(s)
Normal Saline along with standard treatment
Other Intervention Name(s)
Vehicle
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
PMZ-1620 along with standard treatment
Other Intervention Name(s)
Sovateltide (IRL-1620) along with standard treatment
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of PMZ-1620 related adverse events
Description
The primary objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.
Time Frame
90 days
Title
Number of patients not receiving full treatment
Description
Tolerability will be determined by the number of patients that do not receive all the 9 doses of PMZ-1620.
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Changes in clinical progression of International Standards for Neurological Classification of spinal cord injury (ISNCSCI)
Description
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
Time Frame
90 days
Title
Changes in walking index for spinal cord injury (WISCI) score
Description
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.
Time Frame
90 days
Title
Changes in Spinal Cord Independence Measure (SCIM) score
Description
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.
Time Frame
90 days
Title
Changes in MRI/CT
Description
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.
Time Frame
90 days
Title
Changes in electromyography (EMG)
Description
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.
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult males or females aged between 18 and 75 years inclusive
Able to give consent for participation on their own or through their Legally Acceptable Representative (LAR)
Able to cooperate in the completion of a standardized neurological examination by ISNCSCI standards (excludes patients who are on ventilator)
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
Willing and able to comply with the study Protocol
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
Able to receive the Investigational Drug within 48 hours of injury
Neurological Level of Injury between C5-C8, T1-T12, L1-L5 and S1-S5 based upon first ISNCSCI evaluation after arrival to the hospital
Patient with incomplete/partial damage/transaction as shown by CT or MRI scan
Patients with any other chronic conditions, who are stable with appropriate treatment
Exclusion Criteria:
Previous history related to spinal cord disease
Patient on ventilator or requires ventilator
Patient with pathological fracture of vertebral column
Impairment Scale Grade "A" based upon first ISNCSCI assessment and classified as complete injury
One or more upper extremity muscle groups un-testable during baseline ISNCSCI examination
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)
Females who are breastfeeding or have a positive urine pregnancy test
Body mass index (BMI) of ≥35 kg/m2 at screening
Known immunodeficiency, including human immunodeficiency virus, or use of immunosuppressive or cancer chemotherapeutic drugs
Patient having rheumatoid arthritis
The participant has a clinically significant cardiovascular disorder or an abnormal electrocardiogram (ECG) at the discretion of the investigator
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)
Patients who are currently participating in a clinical trial with an investigational drug or investigational device
Patients who, in the opinion of the investigator, are otherwise unsuitable for this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Manish S Lavhale
Phone
+91 9873847397
Email
manish.lavhale@pharmazz.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ravi Kant
Email
ravi.kant@pharmazz.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anil Gulati
Organizational Affiliation
Pharmazz, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
KLE's Dr. Prabhakar Kore Hospital & Medical Research Centre
City
Belgaum
ZIP/Postal Code
590010
Country
India
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sameer Haveri
Phone
+91 9844333082
Email
drsameerhaveri@gmail.com
Facility Name
Institute of Postgraduate Medical Education & Research and SSKM Hospital
City
Kolkata
ZIP/Postal Code
700020
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rajat Choudhuri
Phone
+91 9874660960
Email
rajat.choudhuri@gmail.com
Facility Name
King George's Medical University
City
Lucknow
ZIP/Postal Code
226018
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shah Waliullah
Phone
+91-9335716350
Email
shahwali2008@gmail.com
Facility Name
Rahate Surgical Hospital & ICU
City
Nagpur
ZIP/Postal Code
440008
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ravi P Dashputra
Phone
+91-9823079739
Email
ravidash123@gmail.com
Facility Name
Indian Spinal Injury Centre
City
New Delhi
ZIP/Postal Code
110070
Country
India
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
H.S. Chhabra
Phone
+91 11 42255356
Email
drhschhabra@isiconline.org
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Results will be communicated and published as manuscript
Learn more about this trial
PMZ-1620 (Sovateltide) in Patients of Acute Spinal Cord Injury
We'll reach out to this number within 24 hrs