Long Term Follow-up of Patients With Parkinson's Disease Who Had Administered of A9-DPC in SB-PD-001 Study

Long Term Follow-up of Patients With Parkinson's Disease Who Had Administered of Allogenic Embryonic Stem Cell-derived A9 Dopamine Progenitor Cell (A9-DPC) in SB-PD-001 Study

1. Long-term follow-up period: Approximately 72 months from the date of approval by the Institutional Review Board (IRB)( Study Period: From the A9-DPC treatment date of the first subject in SB-PD-001 Study* up to 5 years after the A9-DPC treatment of the last subject )
2. Objectives: This study aims to evaluate the long-term safety of A9-DPC by following up on the occurrence of adverse event of special interest, (AESI)* for 5 years from A9-DPC treatment date in subjects who have participated in SB-PD-001 Study and received A9-DPC. In addition, it will determine motor and non-motor symptoms over time following A9-DPC treatment, as measured by MDS-UPDRS.
3. Methods of the Long-term Follow-up : This is a single center, open-label, 5-year long-term follow-up to evaluate the long-term safety in subjects receiving A9-DPC in SB-PD-001 Study.

Among subjects who have received A9-DPC, those who have provided voluntary written informed consent for participation of the long-term follow-up will be included. The occurrence of AESIs is investigated for 5 years from A9-DPC treatment, and MDS-UPDRS will be conducted for the efficacy assessment if the study can be conducted.

To avoid any missing data about AESIs, a phone or site visit will be performed at least once yearly from the start of the follow-up.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson's Disease
• Intervention / Treatment: Biological: Allogenic embryonic stem cellderived A9 dopamine progenitor cell (A9-DPC)_Low Dose; Biological: Allogenic embryonic stem cellderived A9 dopamine progenitor cell (A9-DPC)_High Dose

Detailed Description

1. Population of the Long-term Follow-up : Subjects who have participated in SB-PD-001 Study and received A9-DPC (about 12 subjects)

2. Long-term Follow-up Period ; Approximately 72 months from the date of approval by the Institutional Review Board (IRB)

   • Study Period: From the A9-DPC treatment date of the first subject in SB-PD-001 Study* up to 5 years after the A9-DPC treatment of the last subject
   • Study Duration for Individual Subject: 5 years from A9-DPC treatment date * SB-PD-001 Study: Phase 1/2a study of A9-DPC

3. Objectives and Endpoints of the Long-term Follow-up ; This study aims to evaluate the long-term safety of A9-DPC by following up on the occurrence of adverse event of special interest, (AESI)* for 5 years from A9-DPC treatment date in subjects who have participated in SB-PD-001 Study and received A9-DPC. In addition, it will determine motor and non-motor symptoms over time following A9-DPC treatment, as measured by MDS-UPDRS.

   * AESI is a minimum investigation item to be observed for long-term follow-up of stem cell treatment among the adverse events (AEs) that occur in the subjects receiving treatment. In accordance with the Guideline for Long-term Follow-up of Advanced Biopharmaceuticals distributed by the Ministry of Food and Drug Safety in 2020, it is designated as below in this long-term follow-up. AESIs refer to the serious adverse events (SAEs) in the guideline.

   Adverse Event of Special Interests (AESIs)

   [Early-onset AESIs (up to 2 years* after the study drug treatment)]

   • Infectious diseases
   • Complications related to the associated surgical procedures

   [Late-onset AESIs (up to 5 years after the study drug treatment)]

   • Death
   • Generation of a neoplasm or malignant tumor in tissues or organs
   • Onset of an immune reaction including worsening of a previous autoimmune disease or new occurrence
   • Other delayed AESIs related to the treatment of embryonic stem cell-derived therapeutics.

   There is no delayed AESIs confirmed so far, and when any additional AESIs are detected in the subsequent follow-up, they will be added.

4. Drug under Long-term Follow-up ; Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC)

5. Inclusion Criteria ;

   • Persons who have participated in SB-PD-001 Study and received A9-DPC
   • Persons who have provided written informed consent for this long-term follow-up

6. Methods of the Long-term Follow-up ; This is a single center, open-label, 5-year long-term follow-up to evaluate the long-term safety in subjects receiving A9-DPC in SB-PD-001 Study.

   Among subjects who have received A9-DPC, those who have provided voluntary written informed consent for participation of the long-term follow-up will be included. The occurrence of AESIs is investigated for 5 years from A9-DPC treatment, and MDS-UPDRS will be conducted for the efficacy assessment if the study can be conducted.

   To avoid any missing data about AESIs, a phone or site visit will be performed at least once yearly from the start of the follow-up.

7. Analysis Methods ; Adverse Event of Special Interests (AESIs) For AESIs, the number of subjects affected, incidence rate, its exact 95% confidence interval (CI), and the number of events will be provided. In addition, the events will be coded using the Medical Dictionary For Regulatory Activities (MedDRA) with System Organ Class (SOC) and Preferred Term (PT), and the number of subjects affected, incidence rate, and the number of events will be provided.

MDS-UPDRS Total Score(defined On/Off), part Ⅲ (defined on/off) and IV score For changes at each time point after the IP treatment from baseline, descriptive statistics (number of subjects, mean, standard deviation, median, minimum, and maximum) will be provided.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Yonsei Universitiy Health System, Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Persons who have participated in SB-PD-001 Study and received A9-DPC.
• Persons who have provided written informed consent for this long-term follow-up.

Exclusion Criteria:

• Not Applicable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose Group; IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC); Study group : 6 subjects; Dosage: 3.15X10^6 cells/body (6 tracks in total, 52.5X10^4 cells per track)	Biological: Allogenic embryonic stem cellderived A9 dopamine progenitor cell (A9-DPC)_Low Dose; IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC); Main ingredients and quantities: A9-DPC-Low Dose : 7.0X10^6 cells (Use 3.15X10^6 cells of this); Formulation: milky white cell suspension; Storage method: Refrigerated storage (5±3℃); Expiration date: within 36 hours of manufacture; Frequency: single dosing; Method: The subject pierces a burr hole in the skull on the day of surgery. Then the cells are injected at a predetermined stem cell administration point of the putamen in the brain of the subject. One side is administered in three tracks per putamen (6 tracks total brain). Do the same for the other side.
Experimental: High Dose Group; IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC); Study group : 6 subjects; Dosage: 6.30X10^6 cells/body (6 tracks in total, 105X10^4 cells per track)	Biological: Allogenic embryonic stem cellderived A9 dopamine progenitor cell (A9-DPC)_High Dose; IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC); Main ingredients and quantities: A9-DPC-High Dose : 1.4X10^7 cells (Use 6.30X10^6 cells of this); Formulation: milky white cell suspension; Storage method: Refrigerated storage (5±3℃); Expiration date: within 36 hours of manufacture; Frequency: single dosing; Method: The subject pierces a burr hole in the skull on the day of surgery. Then the cells are injected at a predetermined stem cell administration point of the putamen in the brain of the subject. One side is administered in three tracks per putamen (6 tracks total brain). Do the same for the other side.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event of Special Interests (AESIs)	Review occurrence of adverse event of special interests (AESIs)	5 years after IP administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MDS-UPDRS Total Score (defined On/Off)	Present descriptive statistics (number of subjects, average, standard deviation, median, minimum, maximum) by each dose group about changes in the MDS-UPDRS Total Scores, up to 96 Weeks (24 months) after IP administration compared to baseline (-Day 14 to -Day 4).; Defined-on condition: condition that the most positive functional effect, as agreed by the subject and the tester, after treatment with drugs for controlling the symptoms of Parkinson's disease; Defined-off condition: condition after 12 hours off drugs for controlling the symptoms of Parkinson's disease	-Day 14 to -Day 4, 5 years after IP administration
MDS-UPDRS part Ⅲ (defined On/Off)	Present descriptive statistics (number of subjects, average, standard deviation, median, minimum, maximum) by each dose group about changes in the MDS-UPDRS part Ⅲ (defined On/Off) up to 96 Weeks (24 months) after IP administration compared to baseline (-Day 14 to -Day 4).; Defined-on condition: condition that the most positive functional effect, as agreed by the subject and the tester, after treatment with drugs for controlling the symptoms of Parkinson's disease; Defined-off condition: condition after 12 hours off drugs for controlling the symptoms of Parkinson's disease	-Day 14 to -Day 4, 5 years after IP administration
MDS-UPDRS Ⅳ score	Present descriptive statistics (number of subjects, average, standard deviation, median, minimum, maximum) by each dose group about changes in the MDS-UPDRS Ⅳ score up to 96 Weeks (24 months) after IP administration compared to baseline (-Day 14 to -Day 4).; Defined-on condition: condition that the most positive functional effect, as agreed by the subject and the tester, after treatment with drugs for controlling the symptoms of Parkinson's disease; Defined-off condition: condition after 12 hours off drugs for controlling the symptoms of Parkinson's disease	-Day 14 to -Day 4, 5 years after IP administration

Collaborators and Investigators

• Sponsor: S.Biomedics Co., Ltd.
• Collaborators: Severance Hospital
• Investigators: Principal Investigator: Phil-hyu Lee, M.D.,Ph.D, Yonsei Universitiy Health System, Severance Hospital

Publications and helpful links

General Publications

• Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N; Movement Disorder Society UPDRS Revision Task Force. Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord. 2008 Nov 15;23(15):2129-70. doi: 10.1002/mds.22340.
• Schweitzer JS, Song B, Herrington TM, Park TY, Lee N, Ko S, Jeon J, Cha Y, Kim K, Li Q, Henchcliffe C, Kaplitt M, Neff C, Rapalino O, Seo H, Lee IH, Kim J, Kim T, Petsko GA, Ritz J, Cohen BM, Kong SW, Leblanc P, Carter BS, Kim KS. Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson's Disease. N Engl J Med. 2020 May 14;382(20):1926-1932. doi: 10.1056/NEJMoa1915872.
• Kikuchi T, Morizane A, Doi D, Magotani H, Onoe H, Hayashi T, Mizuma H, Takara S, Takahashi R, Inoue H, Morita S, Yamamoto M, Okita K, Nakagawa M, Parmar M, Takahashi J. Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model. Nature. 2017 Aug 30;548(7669):592-596. doi: 10.1038/nature23664.
• Mendez I, Sanchez-Pernaute R, Cooper O, Vinuela A, Ferrari D, Bjorklund L, Dagher A, Isacson O. Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease. Brain. 2005 Jul;128(Pt 7):1498-510. doi: 10.1093/brain/awh510. Epub 2005 May 4.
• Yasuhara T, Kameda M, Sasaki T, Tajiri N, Date I. Cell Therapy for Parkinson's Disease. Cell Transplant. 2017 Sep;26(9):1551-1559. doi: 10.1177/0963689717735411.
• National Institute of Food and Drug Safety, Ministry of Food and Drug Safety, Guideline for Long-term Follow-up of Advanced Biopharmaceuticals 2020.12
• Korea National Institute for Bioethics Policy, Instruction for Protection of Vulnerable Subjects 2019.7
• MDS-UPDRS Korean Official Translation. Last updated May 18, 2020.
• NCI-CTCAE v5.0 [Common Terminology Criteria for Adverse Events (CTCAE) (cancer.gov)]

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2023
• Primary Completion (Estimated): February 7, 2029
• Study Completion (Estimated): June 29, 2029

Study Registration Dates

• First Submitted: June 12, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): July 26, 2024
• Last Update Submitted That Met QC Criteria: July 25, 2024
• Last Verified: June 1, 2024

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; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Cardiotonic Agents; Dopamine Agents; Sympathomimetics; Dopamine
• Other Study ID Numbers: SB-PD-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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