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

NCT ID: NCT06477744

Last Updated: 2024-07-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-09-14
• Study Completion Date: 2029-06-29

Brief Summary

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.

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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Low Dose Group

1. IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC)

2. Study group : 6 subjects

3. Dosage: 3.15X10^6 cells/body (6 tracks in total, 52.5X10^4 cells per track)

Group Type: EXPERIMENTAL

Allogenic embryonic stem cellderived A9 dopamine progenitor cell (A9-DPC)_Low Dose

Intervention Type: BIOLOGICAL

1. IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC)

2. Main ingredients and quantities: A9-DPC

-Low Dose : 7.0X10^6 cells (Use 3.15X10^6 cells of this)

3. Formulation: milky white cell suspension

4. Storage method: Refrigerated storage (5±3℃)

5. Expiration date: within 36 hours of manufacture

6. Frequency: single dosing

7. 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.

High Dose Group

1. IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC)

2. Study group : 6 subjects

3. Dosage: 6.30X10^6 cells/body (6 tracks in total, 105X10^4 cells per track)

Group Type: EXPERIMENTAL

Allogenic embryonic stem cellderived A9 dopamine progenitor cell (A9-DPC)_High Dose

Intervention Type: BIOLOGICAL

1. IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC)

2. Main ingredients and quantities: A9-DPC

-High Dose : 1.4X10^7 cells (Use 6.30X10^6 cells of this)

3. Formulation: milky white cell suspension

4. Storage method: Refrigerated storage (5±3℃)

5. Expiration date: within 36 hours of manufacture

6. Frequency: single dosing

7. 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.

Interventions

Allogenic embryonic stem cellderived A9 dopamine progenitor cell (A9-DPC)_Low Dose

1. IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC)

2. Main ingredients and quantities: A9-DPC

-Low Dose : 7.0X10^6 cells (Use 3.15X10^6 cells of this)

3. Formulation: milky white cell suspension

4. Storage method: Refrigerated storage (5±3℃)

5. Expiration date: within 36 hours of manufacture

6. Frequency: single dosing

7. 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.

Intervention Type: BIOLOGICAL

Allogenic embryonic stem cellderived A9 dopamine progenitor cell (A9-DPC)_High Dose

1. IP Name : Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC)

2. Main ingredients and quantities: A9-DPC

-High Dose : 1.4X10^7 cells (Use 6.30X10^6 cells of this)

3. Formulation: milky white cell suspension

4. Storage method: Refrigerated storage (5±3℃)

5. Expiration date: within 36 hours of manufacture

6. Frequency: single dosing

7. 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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Severance Hospital

OTHER

Sponsor Role: collaborator

S.Biomedics Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Phil-hyu Lee, M.D.,Ph.D

Role: PRINCIPAL_INVESTIGATOR

Yonsei Universitiy Health System, Severance Hospital

Locations

Yonsei Universitiy Health System, Severance Hospital

Seoul, , South Korea

Countries

South Korea

References

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.

Reference Type: BACKGROUND

PMID: 15872020 (View on PubMed)

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.

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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.

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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.

Reference Type: BACKGROUND

PMID: 28858313 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19025984 (View on PubMed)

National Institute of Food and Drug Safety, Ministry of Food and Drug Safety, Guideline for Long-term Follow-up of Advanced Biopharmaceuticals 2020.12

Reference Type: BACKGROUND

Korea National Institute for Bioethics Policy, Instruction for Protection of Vulnerable Subjects 2019.7

Reference Type: BACKGROUND

MDS-UPDRS Korean Official Translation. Last updated May 18, 2020.

Reference Type: BACKGROUND

NCI-CTCAE v5.0 [Common Terminology Criteria for Adverse Events (CTCAE) (cancer.gov)]

Reference Type: BACKGROUND

Other Identifiers

SB-PD-002

Identifier Type: -

Identifier Source: org_study_id