A Study to Evaluate the Safety of Neural Stem Cells in Patients With Parkinson's Disease
Primary Purpose
Parkinson Disease
Status
Unknown status
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
ISC-hpNSC
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent form (ICF) indicating the patient has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
- Patient diagnosed with idiopathic PD of ≤ 13 years duration, as defined by the United Kingdom (UK) Parkinson's Disease Society Brain Bank criteria
- Outpatients (male and female) 30 - 70 years old. Females must be of non-child bearing potential, or with a negative pregnancy test and not breast-feeding
- Patients receiving a stable dose of levodopa for at least 3 months with the expectation that the treatment will remain unchanged throughout the course of the patient's participation in the trial
- Patients receiving an anti-parkinsonian treatment at a stable dose for at least 3 months with the expectation that the treatment will remain unchanged throughout the course of the patient's participation in the trial
- Hoehn and Yahr stage II-IV during "ON" time
- Unified Parkinson's Disease Rating Scale (UPDRS) motor score (Part III) in the "OFF" state ≤ 49
- Positive dopaminergic response of ≥ 33% decrease in UPDRS motor scores between "OFF" and "ON" states at screening, and unequivocal clinical off periods
- Patient is experiencing motor fluctuations with at least two cumulative hours of daily "OFF" -time during the waking period, which is measured on at least two consecutive days
- History of anti-parkinsonian treatment with sufficient doses of levodopa
- Stable, well-controlled concomitant disorders that would not contraindicate general anesthesia or stereotactic neurosurgery
- No abnormalities on baseline brain MRI
- Insufficient control of PD symptoms or intolerable side effects with optimized oral PD therapy
- Montreal Cognitive Assessment (MOCA) score ≥ 26
- Willing to fully comply with all study procedures and requirements of the trial
- No surgery for PD or been treated with neuroleptics in the past 6 months except low-dose quetiapine fumarate or clozapine
- No significant further improvement with physical therapy/rehabilitation
Exclusion Criteria:
- Mild cognitive impairment of dementia (MOCA score < 26)
- The extent or severity of the disease is not measurable
- Severe dyskinesia in the "OFF" or "ON" states (violent dyskinesias, incompatible with any normal motor task)
- Pre-existing medical conditions such as bleeding disorders, septicemia, major cardiovascular, cerebrovascular or psychiatric disease
- Any current or relevant previous history of serious, severe or unstable physical or psychiatric illness or medical disorder that may make the participant unlikely to fully complete the study (depression, anxiety, cognitive impairment or impulse control disorder)
- Clinically significant abnormal hematologic evaluation (blood count, partial thromboplastin time (PTT)), blood chemistry (glucose, blood urea nitrogen (BUN), creatinine, electrolytes), liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGTP), total protein, bilirubin)
- Any active infectious disease of any nature, including clinically active viral infections (seropositive for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B Virus (HBV) and Syphilis
- Severe obesity
- Previous intracranial surgery, including deep-brain stimulation
- History of seizures
- Substance abuse (recent history of alcohol abuse or other drugs such as barbiturates, cannabinoids and amphetamines)
- Use of anti-platelet agents or other anti-coagulants
- Signs of any malignant disease
- Any use of immunosuppressive drugs
- Enrollment in other investigational drug trial or has completed any trial within the last 3 months
- Patients that cannot undergo MRI or PET scanning (i.e. patients with implanted pacemakers)
- Patients unable to travel to the PET scanning center
- Any other condition which clinician regards as making patient unsuitable for trial
Sites / Locations
- Dept of Neurology, The Royal Melbourne Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ISC-hpNSC
Arm Description
Outcomes
Primary Outcome Measures
Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, related TEAEs, severe TEAEs
Secondary Outcome Measures
Change in UPDRS score from baseline
Proportion of patients with improvement defined as any reduction in UPDRS motor score
Full Information
NCT ID
NCT02452723
First Posted
May 18, 2015
Last Updated
April 3, 2019
Sponsor
Cyto Therapeutics Pty Limited
1. Study Identification
Unique Protocol Identification Number
NCT02452723
Brief Title
A Study to Evaluate the Safety of Neural Stem Cells in Patients With Parkinson's Disease
Official Title
A Single Arm, Open-Label Phase 1 Study to Evaluate the Safety and Tolerability of ISC-hpNSC Injected Into the Striatum and Substantia Nigra of Patients With Parkinson's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 2016 (Actual)
Primary Completion Date
April 2020 (Anticipated)
Study Completion Date
June 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cyto Therapeutics Pty Limited
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study will evaluate the safety of an investigational cell transplantation therapy, ISC-hpNSC, in patients with Parkinson's disease. All patients will receive the therapy, which consists of human neural stem cells. Three dose levels will be examined in the study.
Detailed Description
ISC-hpNSC is a cellular therapeutic consisting of human parthenogenetic neural stem cells (hpNSC). ISC-hpNSC will be injected intracerebrally to the striatum and substantia nigra of patients with Parkinson's disease (PD).
The study will enroll 4 patients for cell injection at each of three different doses. A total of 12 patients with moderate to severe PD will be treated. Each patient receives a single dose. The main objective of the study is to evaluate the safety of the cell transplantation.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ISC-hpNSC
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
ISC-hpNSC
Primary Outcome Measure Information:
Title
Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, related TEAEs, severe TEAEs
Time Frame
12 month
Secondary Outcome Measure Information:
Title
Change in UPDRS score from baseline
Time Frame
Baseline and 12 months
Title
Proportion of patients with improvement defined as any reduction in UPDRS motor score
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent form (ICF) indicating the patient has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts
Patient diagnosed with idiopathic PD of ≤ 13 years duration, as defined by the United Kingdom (UK) Parkinson's Disease Society Brain Bank criteria
Outpatients (male and female) 30 - 70 years old. Females must be of non-child bearing potential, or with a negative pregnancy test and not breast-feeding
Patients receiving a stable dose of levodopa for at least 3 months with the expectation that the treatment will remain unchanged throughout the course of the patient's participation in the trial
Patients receiving an anti-parkinsonian treatment at a stable dose for at least 3 months with the expectation that the treatment will remain unchanged throughout the course of the patient's participation in the trial
Hoehn and Yahr stage II-IV during "ON" time
Unified Parkinson's Disease Rating Scale (UPDRS) motor score (Part III) in the "OFF" state ≤ 49
Positive dopaminergic response of ≥ 33% decrease in UPDRS motor scores between "OFF" and "ON" states at screening, and unequivocal clinical off periods
Patient is experiencing motor fluctuations with at least two cumulative hours of daily "OFF" -time during the waking period, which is measured on at least two consecutive days
History of anti-parkinsonian treatment with sufficient doses of levodopa
Stable, well-controlled concomitant disorders that would not contraindicate general anesthesia or stereotactic neurosurgery
No abnormalities on baseline brain MRI
Insufficient control of PD symptoms or intolerable side effects with optimized oral PD therapy
Montreal Cognitive Assessment (MOCA) score ≥ 26
Willing to fully comply with all study procedures and requirements of the trial
No surgery for PD or been treated with neuroleptics in the past 6 months except low-dose quetiapine fumarate or clozapine
No significant further improvement with physical therapy/rehabilitation
Exclusion Criteria:
Mild cognitive impairment of dementia (MOCA score < 26)
The extent or severity of the disease is not measurable
Severe dyskinesia in the "OFF" or "ON" states (violent dyskinesias, incompatible with any normal motor task)
Pre-existing medical conditions such as bleeding disorders, septicemia, major cardiovascular, cerebrovascular or psychiatric disease
Any current or relevant previous history of serious, severe or unstable physical or psychiatric illness or medical disorder that may make the participant unlikely to fully complete the study (depression, anxiety, cognitive impairment or impulse control disorder)
Clinically significant abnormal hematologic evaluation (blood count, partial thromboplastin time (PTT)), blood chemistry (glucose, blood urea nitrogen (BUN), creatinine, electrolytes), liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGTP), total protein, bilirubin)
Any active infectious disease of any nature, including clinically active viral infections (seropositive for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B Virus (HBV) and Syphilis
Severe obesity
Previous intracranial surgery, including deep-brain stimulation
History of seizures
Substance abuse (recent history of alcohol abuse or other drugs such as barbiturates, cannabinoids and amphetamines)
Use of anti-platelet agents or other anti-coagulants
Signs of any malignant disease
Any use of immunosuppressive drugs
Enrollment in other investigational drug trial or has completed any trial within the last 3 months
Patients that cannot undergo MRI or PET scanning (i.e. patients with implanted pacemakers)
Patients unable to travel to the PET scanning center
Any other condition which clinician regards as making patient unsuitable for trial
Facility Information:
Facility Name
Dept of Neurology, The Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
12. IPD Sharing Statement
Citations:
PubMed Identifier
29882481
Citation
Garitaonandia I, Gonzalez R, Sherman G, Semechkin A, Evans A, Kern R. Novel Approach to Stem Cell Therapy in Parkinson's Disease. Stem Cells Dev. 2018 Jul 15;27(14):951-957. doi: 10.1089/scd.2018.0001.
Results Reference
derived
PubMed Identifier
27686862
Citation
Garitaonandia I, Gonzalez R, Christiansen-Weber T, Abramihina T, Poustovoitov M, Noskov A, Sherman G, Semechkin A, Snyder E, Kern R. Neural Stem Cell Tumorigenicity and Biodistribution Assessment for Phase I Clinical Trial in Parkinson's Disease. Sci Rep. 2016 Sep 30;6:34478. doi: 10.1038/srep34478.
Results Reference
derived
PubMed Identifier
27213850
Citation
Gonzalez R, Garitaonandia I, Poustovoitov M, Abramihina T, McEntire C, Culp B, Attwood J, Noskov A, Christiansen-Weber T, Khater M, Mora-Castilla S, To C, Crain A, Sherman G, Semechkin A, Laurent LC, Elsworth JD, Sladek J, Snyder EY, Redmond DE Jr, Kern RA. Neural Stem Cells Derived from Human Parthenogenetic Stem Cells Engraft and Promote Recovery in a Nonhuman Primate Model of Parkinson's Disease. Cell Transplant. 2016 Nov;25(11):1945-1966. doi: 10.3727/096368916X691682.
Results Reference
derived
Learn more about this trial
A Study to Evaluate the Safety of Neural Stem Cells in Patients With Parkinson's Disease
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