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

NCT ID: NCT04052737

Last Updated: 2023-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-23
• Study Completion Date: 2023-01-06

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.

Detailed Description

Alzheimer's is not just a disease of old age, approximately 200,000 Americans under the age of 65 having younger-onset Alzheimer's disease (AD). In 2015, there were approximately 29.8 million people worldwide with AD. The person with Alzheimer's disease can live an average of eight years after their symptoms become noticeable to others, but survival range is 4 to 20 years, depending on the age and other health conditions (www.alz.org). The pathophysiology of AD is related to the injury and death of neurons, initiating in the hippocampus brain region that is involved with memory and learning, then atrophy affects the entire brain. The cause of Alzheimer's disease is still poorly understood and about 70% of the risk is associated with genetic. Other risk factors may also associate with this like history of head injuries, depression, or hypertension. Like all types of dementia, Alzheimer's is also caused by brain cell death. Although AD is classified as a neurodegenerative dementia, considerable evidence links vascular dysfunction and vascular risk factors as pathogenesis of AD. However, it is a progressive brain cell death that happens over a course of time and treatments can't stop Alzheimer's from progressing, they can temporarily slow the worsening of dementia symptoms and improve quality of life for those with Alzheimer's and their caregivers (www.alz.org; www.who.int).

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

Conditions

Alzheimer Disease; Dementia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Normal Saline

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.

Group Type: ACTIVE_COMPARATOR

Normal Saline along with standard treatment

Intervention Type: 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.

PMZ-1620 (sovateltide)

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.

Group Type: EXPERIMENTAL

PMZ-1620 (sovateltide) along with standard treatment

Intervention Type: 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.

Interventions

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

Intervention Type: DRUG

PMZ-1620 (sovateltide) 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 Alzheimer's disease patients.

Intervention Type: DRUG

Other Intervention Names

Vehicle; IRL-1620

Eligibility Criteria

Inclusion Criteria

1. Adult males or females Aged 45 years through 85 years (have not had their 86th birthday)

2. Men and women with a diagnosis of Alzheimer's disease according to the clinical criteria

3. 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

4. Able to give consent for participation on their own or through their Legally Acceptable Representative

5. 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

6. MMSE score in between 11 to 26 in case of mild to moderate stage of Alzheimer's disease

6. 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

Exclusion Criteria

1. Subjects who have a Mini Mental State Examination (MMSE) score of < 10

2. 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

3. A current Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis of active major depression, schizophrenia or bipolar disorder

4. Other infectious, metabolic or systemic diseases affecting the central nervous system

5. Subjects who have participated in a clinical trial investigating an anti-amyloid agent

6. Subjects who are currently participating in a clinical trial with an investigational drug

7. Subjects who, in the opinion of the physician, are otherwise unsuitable for this study

8. 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

9. 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)

10. 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

11. Clinical or laboratory findings consistent with:

1. Other primary degenerative dementia,

2. Other neurodegenerative condition

3. Seizure disorder

12. Subjects, who are already taking sedatives, antidepressants, antipsychotics and antihistaminic medications

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmazz, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anil Gulati

Role: STUDY_CHAIR

Pharmazz, Inc.

Locations

Post Graduate Institute of Medical Education and Research

Chandigarh, , India

King George's Medical University

Lucknow, , India

Sanjay Gandhi Post Graduate Institute of Medical Sciences

Lucknow, , India

Seth GSMC & KEM Hospital

Mumbai, , India

All India Institute of Medical Sciences

New Delhi, , India

Countries

India

References

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.

Reference Type: BACKGROUND

PMID: 29947531 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26022359 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24561065 (View on PubMed)

Other Identifiers

CTRI/2017/12/011003

Identifier Type: REGISTRY

Identifier Source: secondary_id

PMZ-1620/CLINICAL-2.2/2017

Identifier Type: -

Identifier Source: org_study_id