History of Changes for Study: NCT04802733

A Study to Assess the Safety and Tolerability of Surgical Implant of MSK-DA01 Cells for Advanced Parkinson's Disease

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Study Record Versions

Version	Submitted Date	Changes
1	March 15, 2021	None (earliest Version on record)
2	March 22, 2021	Contacts/Locations, Outcome Measures, Arms and Interventions, Study Status, Study Identification, Sponsor/Collaborators, IPDSharing, Conditions, Study Description, Oversight, References, Eligibility and Study Design
3	March 26, 2021	Recruitment Status, Study Status and Contacts/Locations
4	May 10, 2021	Study Status
5	June 9, 2021	Contacts/Locations, Study Status and Eligibility
6	June 21, 2021	Contacts/Locations and Study Status
7	August 23, 2021	Contacts/Locations and Study Status
8	August 31, 2021	Contacts/Locations and Study Status
9	October 25, 2021	Contacts/Locations and Study Status
10	November 10, 2021	Study Status and Study Design
11	January 6, 2022	Contacts/Locations and Study Status
12	March 23, 2022	Study Status and Eligibility
13	May 31, 2022	Recruitment Status, Study Status, Contacts/Locations and Study Design

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Merged
Side-by-Side

Study Identification


Unique Protocol ID:	18-518
Brief Title:	A Study to Assess the Safety and Tolerability of Surgical Implant of MSK-DA01 Cells for Advanced Parkinson's Disease
Official Title:	Phase 1 Study To Assess the Safety and Tolerability of Human Embryonic Stem Cell-Derived Midbrain Dopamine Neuron Cell Therapy (MSK-DA01) For Advanced Parkinson's Disease
Secondary IDs:

Study Status


Record Verification:	March 2021
Overall Status:	Not yet recruiting
Study Start:	April 2021
Primary Completion:	April 2023 [Anticipated]
Study Completion:	April 2023 [Anticipated]

First Submitted:	March 12, 2021
First Submitted that Met QC Criteria:	March 15, 2021
First Posted:	March 17, 2021 [Actual]

Last Update Submitted that Met QC Criteria:	March 15, 2021
Last Update Posted:	March 17, 2021 [Actual]

Sponsor/Collaborators


Sponsor:	Memorial Sloan Kettering Cancer Center
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:

Study Description


Brief Summary:	The main purpose of this study is to test the safety and tolerability of the study intervention, MSK-DA01, which will be implanted into the brain of study participants during a surgical procedure. This study is the first time that MSK-DA01 is being tested in people.
Detailed Description:

Conditions


Conditions:	Parkinson's Disease
Keywords:	MSK-DA01 Cells Human Embryonic Stem Cell-Derived Midbrain Dopamine Neuron Cell Therapy 18-518

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1
Interventional Study Model:	Single Group Assignment
	Single center (multi-site), open label, non-randomized, non-controlled study.
Number of Arms:	1
Masking:	None (Open Label)
Allocation:	N/A
Enrollment:	10 [Anticipated]

Arms and Interventions

Arms

Assigned Interventions

Experimental: MSK-DA01 Cells for Advanced Parkinson's Disease

Subjects will undergo a single session surgical transplantation of one of two different dose levels of MSK-DA01 cells to the post-commissural putamen bilaterally, and administration of a 1 year immunosuppression regimen. The first 5 subjects (Cohort A) will receive Dose A (0.9 million cells per putamen) and the second 5 (Cohort B) will receive Dose B (2.7 million cells per putamen).

MSK-DA01 Cells

Surgical intracerebral transplantation of MSK-DA01 cells

Drug: Immunosuppressive regimen

Basiliximab 20 mg intravenously intraoperatively and post-op day #4; methylprednisolone 500 mg intravenously prior to surgery, then taper to oral prednisone and continued at 5mg daily for 1 year; tacrolimus 1 mg oral beginning on the day after surgery twice daily, then adjusted to target 4-7 ng/ml for a period of 1 year.

Outcome Measures


Primary Outcome Measures:
1.	incidence of SAEs Cohort A [ Time Frame: at 1-year post-transplant ] Safety will be defined as 2 or less of Cohort A or Cohort B developing 2 or more SAEs related to surgery, presence of transplanted cells, or immunosuppression; as 2 or less of Cohort A or Cohort B developing a tumor or abnormal tissue overgrowth related to presence of transplanted cells;
2.	incidence of SAEs Cohort B [ Time Frame: 1 year post-transplant ] Safety will be defined as 2 or less of Cohort A or Cohort B developing 2 or more SAEs related to surgery, presence of transplanted cells, or immunosuppression; as 2 or less of Cohort A or Cohort B developing a tumor or abnormal tissue overgrowth related to presence of transplanted cells;
Secondary Outcome Measures:
1.	Change in striatal 18F-DOPA uptake using positron emission tomography (PET) [ Time Frame: up to to 2 years ] Change in striatal 18F-DOPA uptake using positron emission tomography (PET) from baseline to 1 and 2 years;

Eligibility


Minimum Age:	60 Years
Maximum Age:	76 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Age ≥60 to ≤76 years old Idiopathic Parkinson's Disease defined by the modified UK Parkinson's Disease Society Brain Bank criteria A minimum time of 5 years from time of PD diagnosis and a maximum time from PD diagnosis of 15 years. Prior sufficient treatment comprising levodopa and at least one adjunct therapy, and additional appropriate therapy such as physical therapy. Defined levodopa response of ≥ 40% improvement on the basis of MDS-UPDRS part 3 Baseline Hoehn & Yahr score 0-2 "on" and 3-4 "off" Not eligible for deep brain stimulation or have refused deep brain stimulation after evaluation by an independent neurologist or neurosurgeon Parkinson's disease medications allowed: any approved oral, transdermal, and/or injectable PD medication and medications must be stable for ≥ 1 month prior to enrollment AIMS rating scale score of ≤ 2 for dyskinesia "Off" time of ≥ 2 hours daily Montreal Cognitive Assessment (MoCA) score ≥ 26 Hamilton Depression Scale (HAM-D) score ≤17 Dysthymia allowed with single or two antidepressant medications if at stable dose for > 6 months Normal endocrine, renal and liver function as measured by standard laboratory testing unless clinically significant, no blood dyscrasias, no bleeding disorder, and no cardiovascular contraindications for surgery, except for stable and controlled conditions including diabetes type 2 and hypothyroidism. All other concomitant disorders must be stable and well controlled, must not constitute a contraindication to general anesthesia or surgery, or interfere with scheduled study assessments Women of child-bearing potential must agree to use a highly effective method of contraception from screening until at least 4 weeks after cessation of the oral immunosuppression medication regimen Able to participate in all study visits and evaluations, including brain MRI Able to give informed consent for study participation and sign Informed Consent Document Existence of a study participant partner who may act as potential surrogate over long term for ongoing consent Exclusion Criteria: Clinical features suggestive of a neurodegenerative diagnosis other than Parkinson's disease Parkinson's disease with only tremor-based symptoms Diagnosis of primary mitochondrial disorder, epilepsy, stroke, multiple sclerosis or other neurodegenerative diseases such as Alzheimer's disease Any current or relevant previous history of serious, severe or unstable physical, neurological, or psychiatric illness that may make the subject unlikely to fully complete the study (including significant depression, psychosis, anxiety, cognitive impairment or impulse control disorder) Receiving dopamine receptor blocking agents, including typical neuroleptics, prochlorperazine, and metoclopramide at the time of screening or within 3 months prior to screening 18F-DOPA PET imaging inconsistent with dopamine deficiency Ongoing treatment with intrajejunal or subcutaneous infusion therapies for PD History of DBS, lesion therapy, or gene therapy for PD Prior surgical or radiation therapy to the brain or spinal cord Per assessing clinician discretion, any abnormality on brain MRI that would preclude cell transplantation Significant concomitant medical disease limiting life expectancy to less than 24 months from study inclusion, or significant and serious concomitant medical disease that is poorly controlled Clinically relevant abnormalities on standard safety laboratory tests, including (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) Presence of a condition resulting in high risk of immunosuppressive drugs, including any Virus (HCV), Hepatitis B Virus (HBV), cytomegalovirus (CMV), and Venereal Disease Research Laboratory (VDRL) unless related to immunization or past CMV exposure, risk of tuberculosis. Inability to temporarily stop anti-platelet agents or other anti-coagulants without significant risk Previous or currently active malignant disease within the past 5 years, except basal cell carcinoma or in situ uterine cervical carcinoma that have been definitively treated Use of immunosuppressive drugs including systemic steroids within the previous 3 months Severe obesity (>350 lbs) or any condition that prevents use of PET/MRI Known substance abuse (recent history of abuse of alcohol or other drugs such as barbiturates, cannabinoids and amphetamines) within last 5 years In the opinion of the investigator, presence of any cognitive, behavioral, or psychiatric symptoms that would be deemed contraindications to cell transplantation Pregnancy or breastfeeding Unable to cooperate or complete self-assessment scales and diaries Unable to provide and sign informed consent Receipt of another investigational agent or device within the 3 months prior to enrollment Contraindication to surgery or general anesthesia Contraindication to taking immunosuppressive drugs In the opinion of the investigator, any other condition regarded as making subject unsuitable for trial

Contacts/Locations


Central Contact Person:	Harini Sarva, MD Telephone: 212-639-3006 Email: sarvah@mskcc.org
Central Contact Backup:	Mark Souweidane, MD Telephone: 212-639-7056
Study Officials:	Harini Sarva, MD Principal Investigator Memorial Sloan Kettering Cancer Center
Locations:	United States, New York
	Memorial Sloan Kettering Cancer Center New York, New York, United States, 10065 Contact:Contact: Harini Sarva,, MD 212-639-3006
	Weill Cornell Medical College New York, New York, United States, 10065 Contact:Contact: Harini Sarva, MD 212-746-2584

IPDSharing


Plan to Share IPD:	Yes Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
	Supporting Information:
	Time Frame:
	Access Criteria:
	URL:

References


Citations:
Links:	URL: http://www.mskcc.org/mskcc/html/44.cfm Description: Memorial Sloan Kettering Cancer Center
Available IPD/Information: