Safety and Efficacy Study of Human ESC-derived Neural Precursor Cells in the Treatment of Parkinson's Disease

A Phase I/II, Open-Label Study to Assess the Safety and Efficacy of Striatum Transplantation of Human Embryonic Stem Cells-derived Neural Precursor Cells in Patients With Parkinson's Disease

This study will evaluate the safety and efficacy of intracerebral transplantation of human embryonic stem cells-derived neural precursor cells in patients with Parkinson's Disease.

Study Overview

• Status: Unknown
• Conditions: Parkinson's Disease
• Intervention / Treatment: Biological: NPC transplantation; Drug: Levodopa

Detailed Description

This study is a Phase I/II, open-label, non randomized clinical trial. The study will enroll 50 patients for cell injection, administering a single dose of neural precursor cells by stereotaxic intra-striatal injection.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Primary Parkinson's disease patients，a history over 5 years，females or males;
2. Cannot effectively control the PD or tolerate the side effects of drugs;
3. Hoehn and Yahr Stage 3 or 4 in the off state at screening
4. Age between 50 and 80 years;
5. Dopamine is effective or once;
6. Sign the informed consent

Exclusion Criteria:

1. Atypical Parkinsonian syndrome or only having tremor syndrome;
2. Having been done pallidotomy, DBS, striatum or extrapyramidal surgery;
3. Subjects are using apomorphine or anticoagulant;
4. Subjects used immunosuppressant or antipsychotic drugs in last 3 months;
5. Subjects used botulinum toxin, phenol, or other drugs for the treatment of dystonia or muscle cramps in last 6 months;
6. During the period of active epilepsy preventing epilepsy with antiepileptic;
7. Coagulant function abnormality or other obviously abnormal laboratory test results;
8. Having skin basal cell carcinoma or cervical cancer and other pre-cancerous lesions;
9. Subject has a history of chronic alcohol or drug abuse ;
10. Pregnancy or lactation;
11. Subjects participated in other clinical trials in recent 3 months;
12. Subject is considered as dementia, a serious mental disorder (depression or mania), and personality or behavioral disorders through cognitive and behavioral test;
13. Cannot cooperate on the research;
14. Severe brain atrophy, or existing brain injury such as cerebral infarction, cerebral vascular malformation or trauma;
15. Severe systemic diseases;
16. Severe dyskinesia or frequent "OFF" or "ON" states
17. Severe infectious diseases (eg HIV, HCV, HBV, syphilis positive)
18. Not suitable to participate in this clinical trial assessed by other physicians

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NPC transplantation; The patients will receive Levodopa combined with a regular neural precursor cell (NPC) transplantation	Biological: NPC transplantation; The cells are stereotactically implanted in the striatum.; Drug: Levodopa; Levodopa is used depending on the patient's condition
EXPERIMENTAL: HLA-matched NPC transplantation; The patients will receive Levodopa combined with a HLA-matched neural precursor cell (NPC) transplantation	Biological: NPC transplantation; The cells are stereotactically implanted in the striatum.; Drug: Levodopa; Levodopa is used depending on the patient's condition
EXPERIMENTAL: HLA-non-matched NPC transplantation; The patients will receive Levodopa combined with a HLA-non-matched neural precursor cell (NPC) transplantation	Biological: NPC transplantation; The cells are stereotactically implanted in the striatum.; Drug: Levodopa; Levodopa is used depending on the patient's condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs), severe TEAEs as assessed by head MRI and blood examination	Number of subjects with adverse events such as the evidence of graft failure or rejection	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Unified Parkinson's Disease Rating Scale (UPDRS) score from baseline	The total Unified Parkinson's Disease Rating Scale (UPDRS) score is derived from Part I (Mentation, Behavior and Mood), Part II (Activities of Daily Living) and Part III (Motor Examination). Part I assesses 4 functions; Part II assesses 13 activities of daily living; Part III assesses 14 motor symptoms. Each item is rated on a scale from 0 (normal) to 4 (severe). The minimum total score possible is 0 and the maximum total score possible is 176. Each subject was independently rated by two observers at each study visit and a mean score was calculated for analysis.	Baseline and 12 months
Change in DATscan from baseline	DATscan is an imaging technology that uses small amounts of a radioactive drug to help determine how much dopamine is available in a person's brain.Its principle is based on using of radiopharmaceutical, which bind to dopamine transporters (DAT).	Baseline and 12 months
Change in Hoehn and Yahr Stage from baseline	The Hoehn and Yahr scale is a commonly used system for describing how the symptoms of Parkinson's disease progress mainly by observing balance and walk.	Baseline and 12 months

Collaborators and Investigators

• Sponsor: Chinese Academy of Sciences
• Collaborators: The First Affiliated Hospital of Zhengzhou University

Publications and helpful links

General Publications

• Wang YK, Zhu WW, Wu MH, Wu YH, Liu ZX, Liang LM, Sheng C, Hao J, Wang L, Li W, Zhou Q, Hu BY. Human Clinical-Grade Parthenogenetic ESC-Derived Dopaminergic Neurons Recover Locomotive Defects of Nonhuman Primate Models of Parkinson's Disease. Stem Cell Reports. 2018 Jul 10;11(1):171-182. doi: 10.1016/j.stemcr.2018.05.010. Epub 2018 Jun 14.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): May 1, 2017
• Primary Completion (ANTICIPATED): November 1, 2018
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: April 6, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (ACTUAL): April 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 18, 2017
• Last Update Submitted That Met QC Criteria: April 13, 2017
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa
• Other Study ID Numbers: ChineseASZQ-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No