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 of mild to moderate Alzheimers disease.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
PMZ-01/CLINICAL-2.2/2017, Version 01, Dated 14 June 2017
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Manish S Lavhale
Designation
Associate Director
Affiliation
Pharmazz India Private Limited
Address
H-6, Site-C, Surajpur Industrial Area Greater Noida Gautam Buddha Nagar UTTAR PRADESH 201307 India
Phone
9873847397
Fax
Email
manish.lavhale@pharmazz.com
Details of Contact Person Public Query
Name
Mr Sunil Gulati
Designation
Chief Operating Officer
Affiliation
Pharmazz India Private Limited
Address
H-6, Site-C, Surajpur Industrial Area Greater Noida Gautam Buddha Nagar UTTAR PRADESH 201307 India
Phone
9811406340
Fax
Email
sunil.gulati@pharmazz.com
Source of Monetary or Material Support
Pharmazz India Private Limited, H-6, Site-C, Surajpur Industrial Area, Greater Noida UP 201307
Drug Trial Ethics Committee, Basement, Hero DMC Heart Institute, Opp Library, Dayanand Medical College and Hospital, Tagore Nagar, Civil Lines, Ludhiana 141001, Punjab, India
Approved
Ethics Committee, All India Institute of Medical Sciences, Room No.102, 1st Floor, Old O.T. Block, Ansari Nagar, New Delhi-110029, India
Approved
Ethics Committee, Rahate Surgical Hospital, Conference Room 4th Floor Near Telephone Exchange Square, 517- Juni Mangalwari, Central Avenue, Nagpur 440008, Maharastra
Approved
Institutional Ethics Committee, Seth GS Medical College and KEM Hospital, Parel, Mumbai-400012, India
Approved
Institutional Ethics Committee King Georges Medical University King Georges Medical University Shahmina Road, Chowk, Lucknow Lucknow Uttar Pradesh - 226003 India
Approved
Institutional Ethics Committee S.N Medical S N Medical College Raja Mandi Near Agra College Agra Central Library ,moti Katra Mantola Agra Agra Uttar Pradesh - 282003 India
Approved
INSTITUTIONAL ETHICS COMMITTEE Sanjay Gandhi Postgraduate Institute of M Sciences Raebareli Road Lucknow Uttar Pradesh - 226014 India
Approved
Institutional Ethics Committee, Christian Medical College and Hospital, Brown Road, Ludhiana 141008, Punjab, India
Approved
Institutional Ethics Committee, Postgraduate Institute of Medical Education and Research (PGIMER), Room No.: 6006, Sixth Floor, PN Chuttani Block, Chandigarh 160 012
Approved
People Tree Hospitals Ethics Committee, People Tree Hospitals No -2, Tumkur Road, Opp Taj Vivanta Goraguntepalya Yeshwanthpur Bengaluru 560022 Karnataka India
PMZ-1620 + Standard of care: Three doses of PMZ-1620
(each dose of 0.3 μg/kg body weight) will be administered as an intravenous bolus over
1 minute at an interval of 3±1 hours, once in a month for 6 months.
Comparator Agent
Placebo (Available as a lyophilized
injection containing excipients formulated without active ingredient)
Placebo + Standard of care: Three doses of Placebo (each dose of 0.3 μg/kg body weight) will be administered as an intravenous bolus over 1 minute at an interval of 3±1 hours, once in a month for 6 months.
Inclusion Criteria
Age From
45.00 Year(s)
Age To
85.00 Year(s)
Gender
Both
Details
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 (LAR)
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 Alzheimers disease
7. Absence of major depressive disease according to Geriatric Depression Scale (GDS) of < 5
8. Previous decline in cognition for more than six months as documented in subject’s medical records
9. Subject, who are on stable treatment with any of AD drugs are also eligible to participate in this study
10. Formal education for eight or more years
11. Subjects living at home or nursing home setting, without continuous nursing care
12. General health status acceptable for participation in a 6-months clinical trial
13. 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
14. Subjects with any other chronic conditions are stable and undergoing appropriate treatment
ExclusionCriteria
Details
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:
a. Other primary degenerative dementia,
b. Other neurodegenerative condition
c. Seizure disorder
12. Subjects, who are already taking sedatives, antidepressants, antipsychotics and antihistaminic medications.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Number of adverse events (AEs) and serious adverse events (SAEs), number of subjects with AEs/SAEs, changes in vital signs and laboratory examinations.
6 months
Secondary Outcome
Outcome
TimePoints
Statistically relevant changes in clinical progression of AD as measured by MMSE
After 3 and 6 months of treatment.
Statistically relevant changes in NPI Score
After 3 and 6 months of treatment
Statistically relevant changes in ADAS-Cog
After 3 and 6 months of treatment
Statistically relevant changes in AD symptom progression of dementing process of hippocampal atrophy using MRI/CT
Before and at the end of study
Statistically relevant changes in electroencephalogram(EEG) of brain changes in AD symptom progression
After 3 and 6 months of treatment
Physical examinations of AD symptom progression
In every visits
Target Sample Size
Total Sample Size="80" Sample Size from India="80" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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 AD. A total of 80 subjects (40 in each group) will be enrolled in this study. The enrolment period of the study will be approximately 12 months and total duration of the study will be approximately 18 months. For an individual subject, duration of the study will be 6 months (160 days), including 8 study visits: visit 1/Day 1 (screening/baseline visit), visit 2/Day 2-5 (treatment visit), visit 3/Day 30±3 (treatment visit), visit 4/Day 60±3 (treatment visit), visit 5/Day 90±3 (treatment and assessment visit), visit 6/Day 120±3 (treatment visit), visit 7/Day 150±3 (treatment visit) and final visit 8/End of study Day 157 to 160 (Follow-up visit). At visit 2, subjects will be randomized 1:1 into 2 treatment groups after meeting the eligibility criteria.
Group 1: PMZ-1620 + Standard of care
Group 2: Placebo + Standard of care
After randomization, subjects will be administered with either PMZ-1620 or Placebo, once in a month for 6 months. Three doses of PMZ-1620/Placebo (each dose of 0.3 μg/kg body weight) will be administered as an IV bolus over one minute at an interval of 3±1 hours once in a month (total dose/day: 0.9 μg/kg body weight). Dose will be repeated every month for 6 months post randomization. In both treatment groups, subjects will be provided the best standard of care. Standard of care to be provided to the subjects shall be the one used in the particular hospital setup. Each subject will be monitored closely throughout his/her admission for the qualifying mild to moderate AD and will be followed for 6 months from randomization. Each subject will be assessed for efficacy and safety parameters over 6 months from randomization at a clinic visit.