PMZ-1620 (Sovateltide) in Mild to Moderate Alzheimer's Disease
Condition: Alzheimer Disease; Dementia
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Normal Saline along with standard treatment; PMZ-1620 (sovateltide) along with standard treatment
Intervention type(s): Drug; Drug
Intervention description(s): 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) 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.
Other intervention name(s): Vehicle; IRL-1620
Allocation: Randomized
Intervention model: Parallel Assignment
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 (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.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Endothelin; Neurogenesis; Neural progenitor cells