PMZ-1620 (Sovateltide) in Mild to Moderate Alzheimer's Disease

NCT04052737 | Completed Phase 2 DMC

• 2 other identifiers: PMZ-1620/CLINICAL-2.2/2017CTRI/2017/12/011003
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 5

Brief Summary

This is a prospective, multicentric, randomized, double blind, placebo controlled Phase II clinical study to compare the safety and efficacy of PMZ-1620 therapy along with standard supportive care in subjects with mild to moderate Alzheimer's disease.

Conditions

Alzheimer Disease; Dementia

Keywords

Endothelin; Neurogenesis; Neural progenitor cells

Outcome Measures

Primary Outcomes (2)

• Incidence of PMZ-1620 related adverse events

  The primary objective of the study is to determine incidence of drug (PMZ-1620) related adverse events.

  160 days

• Number of patients not receiving full treatment due to intolerance to PMZ-1620

  Tolerability will be determined by the number of patients that do not receive all the 18 doses of PMZ-1620.

  160 days

Secondary Outcomes (5)

• Changes in clinical progression of AD as measured by Mini-Mental State Examination (MMSE)

  160 days

• Changes in neuropsychiatric inventory (NPI) Score

  160 days

• Changes in Alzheimer's disease Assessment Scale-Cognitive Subscale (ADAS-Cog)

  160 days

• Changes in hippocampal atrophy using MRI/CT

  160 days

• Changes in electroencephalograms (EEGs)

  160 days

Study Arms (2)

Normal Saline

ACTIVE COMPARATOR

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, the same dosing regimen will be repeated every month for 6 months post randomization.

Drug: Normal Saline along with standard treatment

PMZ-1620 (sovateltide)

EXPERIMENTAL

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 (total dose/day: 0.9 µg/kg body weight), the same dosing regimen will be repeated every month for 6 months post randomization.

Drug: PMZ-1620 (sovateltide) along with standard treatment

Interventions

Normal Saline along with standard treatment DRUG

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 Alzheimer's disease patients. In this arm normal saline along with standard treatment will be given for active comparison.

Also known as: Vehicle

Normal Saline

PMZ-1620 (sovateltide) along with standard treatment DRUG

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 Alzheimer's disease patients.

Also known as: IRL-1620

PMZ-1620 (sovateltide)

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males or females Aged 45 years through 85 years (have not had their 86th birthday)
• Men and women with a diagnosis of Alzheimer's disease according to the clinical criteria
• Women must be of non-childbearing potential, 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 give consent for participation on their own or through their Legally Acceptable Representative
• MRI/CT scan assessment within six months before baseline, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions
• MMSE score in between 11 to 26 in case of mild to moderate stage of Alzheimer's disease
• \. Absence of major depressive disease according to Geriatric Depression Scale (GDS) of \< 5 7. Previous decline in cognition for more than six months as documented in subject's medical records 8. Subject, who are on stable treatment with any of AD drugs are also eligible to participate in this study 9. Formal education for eight or more years 10. Subjects living at home or nursing home setting, without continuous nursing care 11. General health status acceptable for participation in a 6-months clinical trial 12. A caregiver available and living in the same household or interacting with the subject a sufficient time each week and available if necessary to assure administration of drug 13. Subjects with any other chronic conditions are stable and undergoing appropriate treatment

You may not qualify if:

• Subjects who have a Mini Mental State Examination (MMSE) score of \< 10
• Subjects who have serious or unstable medical conditions that would exclude completion of all procedures and data collection for the study, or would be likely to preclude participation in a drug development trial
• A current Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis of active major depression, schizophrenia or bipolar disorder
• Other infectious, metabolic or systemic diseases affecting the central nervous system
• Subjects who have participated in a clinical trial investigating an anti-amyloid agent
• Subjects who are currently participating in a clinical trial with an investigational drug
• Subjects who, in the opinion of the physician, are otherwise unsuitable for this study
• Clinically significant, advanced or unstable disease that may interfere with outcome measures, and which may bias the assessment of the clinical or mental status of the subject or put the subject at special risk
• History of or screening brain MRI scan indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct \> 1 cm3, \>3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess or brain tumor such as meningioma)
• Subject has had a myocardial infarction, unstable angina, stroke, transient ischemic attack or required intervention for any of these conditions within 6 months of Screening
• Clinical or laboratory findings consistent with:
• Other primary degenerative dementia,
• Other neurodegenerative condition
• Seizure disorder
• Subjects, who are already taking sedatives, antidepressants, antipsychotics and antihistaminic medications

Sponsors & Collaborators

• Pharmazz, Inc.: lead

Study Sites (5)

Post Graduate Institute of Medical Education and Research

Chandigarh, 160012, India

Location

King George's Medical University

Lucknow, 226003, India

Location

Sanjay Gandhi Post Graduate Institute of Medical Sciences

Lucknow, 226014, India

Location

Seth GSMC & KEM Hospital

Mumbai, 400012, India

Location

All India Institute of Medical Sciences

New Delhi, 110029, India

Location

Related Publications (3)

• Gulati A, Hornick MG, Briyal S, Lavhale MS. A novel neuroregenerative approach using ET(B) receptor agonist, IRL-1620, to treat CNS disorders. Physiol Res. 2018 Jun 27;67(Suppl 1):S95-S113. doi: 10.33549/physiolres.933859.

  PMID: 29947531 BACKGROUND

• Briyal S, Nguyen C, Leonard M, Gulati A. Stimulation of endothelin B receptors by IRL-1620 decreases the progression of Alzheimer's disease. Neuroscience. 2015 Aug 20;301:1-11. doi: 10.1016/j.neuroscience.2015.05.044. Epub 2015 May 27.

  PMID: 26022359 BACKGROUND

• Briyal S, Shepard C, Gulati A. Endothelin receptor type B agonist, IRL-1620, prevents beta amyloid (Abeta) induced oxidative stress and cognitive impairment in normal and diabetic rats. Pharmacol Biochem Behav. 2014 May;120:65-72. doi: 10.1016/j.pbb.2014.02.008. Epub 2014 Feb 20.

  PMID: 24561065 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

sovateltide

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Anil Gulati

  Pharmazz, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 (total dose/day: 0.9 µg/kg body weight). The same dosing regimen will be repeated every month for 6 months post randomization. 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 post randomization. The same dosing regimen will be repeated every month for 6 months post randomization. In both treatment groups, subjects will be provided the best available standard of care.

Study Record Dates

• First Submitted: August 8, 2019
• First Posted: August 12, 2019
• Study Start: March 23, 2018
• Primary Completion: December 20, 2022
• Study Completion: January 6, 2023
• Last Updated: January 12, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (5)