Study to Evaluate the Safety and Efficacy of ESC-derived Dopamine Progenitor Cell Therapy in PD Patients

NCT05887466 | Completed Phase 1 DMC

• 1 other identifier: SB-PD-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

Indication: Patients who were diagnosed with Parkinson's disease ≥ 5 years ago. Purpose: To find the maximum tolerable dose and evaluate the safety and exploratory efficacy of allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC) therapy in patients who were diagnosed with Parkinson's disease ≥ 5 years ago, as a treatment for delaying or stopping the progression of Parkinson's disease or inducing recovery of damaged brain. Number of Subjects: Up to 12 subjects. \[Low dose\] 3.15X10\^6 cells/body: 6 subjects. \[High dose\] 6.30X10\^6 cells/body: 6 subjects. Study Design: Single center, open, single dosing, dose-escalation, phase 1/2a study Endpoints: \[Primary Safety Endpoints\]

1. 1.Occurrence of treatment-emergent adverse events (TEAEs) after administration of the IP
2. 2.Failure or rejection of transplantation and occurrence of bleeding and infection at Week 12 (3months), Week 24 (6months), Week 48 (12months) and Week 96 (24months) after administration of the IP
3. 3.Occurrence of adverse event of special interest (AESI)\* after administration of the IP
4. 4.AESI: a) death, b) generation of a neoplasm or malignant tumor in tissues or organs, c) onset of an immune reaction including worsening of a previous autoimmune disease or new occurrence, and d) other delayed adverse events related to this embryonic stem cell treatment.

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (14)

• Occurrence of treatment-emergent adverse events (TEAEs) after administration of the IP

  Present frequency and percentage by each dose group about occurrence of treatment-emergent adverse events (TEAEs) after administration of the IP

  Up to 96 Weeks (24 months) after IP administration

• Failure or rejection of transplantation

  Present frequency and percentage by each dose group about failure or rejection of transplantation at Week 12 (3 months) after administration of the IP

  Week 12 (3 months)

• Failure or rejection of transplantation

  Present frequency and percentage by each dose group about failure or rejection of transplantation at Week 24 (6 months) after administration of the IP

  Week 24 (6 months)

• Failure or rejection of transplantation

  Present frequency and percentage by each dose group about failure or rejection of transplantation at Week 48 (12 months) after administration of the IP

  Week 48 (12 months)

• Failure or rejection of transplantation

  Present frequency and percentage by each dose group about failure or rejection of transplantation at Week 96 (24 months) after administration of the IP

  Week 96 (24 months)

• Occurrence of bleeding

  Present frequency and percentage by each dose group about occurrence of bleeding at Week 12 (3 months) after administration of the IP

  Week 12 (3 months)

• Occurrence of bleeding

  Present frequency and percentage by each dose group about occurrence of bleeding at Week 24 (6 months) after administration of the IP

  Week 24 (6 months)

• Occurrence of bleeding

  Present frequency and percentage by each dose group about occurrence of bleeding at Week 48 (12 months) after administration of the IP

  Week 48 (12 months)

• Occurrence of bleeding

  Present frequency and percentage by each dose group about occurrence of bleeding at Week 96 (24 months) after administration of the IP

  Week 96 (24 months)

• Occurrence of infection

  Present frequency and percentage by each dose group about occurrence of infection at Week 12 (3 months) after administration of the IP

  Week 12 (3 months)

• Occurrence of infection

  Present frequency and percentage by each dose group about occurrence of infection at Week 24 (6 months) after administration of the IP

  Week 24 (6 months)

• Occurrence of infection

  Present frequency and percentage by each dose group about occurrence of infection at Week 48 (12 months) after administration of the IP

  Week 48 (12 months)

• Occurrence of infection

  Present frequency and percentage by each dose group about occurrence of infection at Week 96 (24 months) after administration of the IP

  Week 96 (24 months)

• Occurrence of adverse event of special interest (AESI)* after administration of the IP

  Present frequency and percentage by each dose group about occurrence of adverse event of special interest (AESI)\* after administration of the IP \*AESI: a) death, b) generation of a neoplasm or malignant tumor in tissues or organs, c) onset of an immune reaction including worsening of a previous autoimmune disease or new occurrence, and d) other delayed adverse events related to this embryonic stem cell treatment.

  Up to 96 Weeks (24 months) after IP administration

Secondary Outcomes (13)

• Change in the MDS-UPDRS Total Score, part Ⅲ (defined on/off) & part Ⅳ

  -Day 14 to -Day 4, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96

• Change in the K-MMSE

  -Day 14 to -Day 4, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96

• Change in the Seoul Neuropsychological screening battery (SNSB, Screening & Week 96 (24 months))

  -Day 14 to -Day 4, Week 96

• Hoehn & Yahr scale

  Day 14 to -Day 4, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96

• Change in the K-MoCA

  -Day 2, Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96

Other Outcomes (3)

• Vital signs

  -Day14 to -Day 4, -Day 2, Day 0 (Postoperative day #0), Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96

• Laboratory tests

  -Day 14 to -Day 4, Day 0 (Postoperative day #0), Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96

• Physical examination

  -Day 14 to -Day 4, -Day 2, Day 0 (Post operative day #0), Week 4, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96

Study Arms (2)

Low Dose Group

EXPERIMENTAL

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)

Biological: Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC) Low Dose

High Dose Group

EXPERIMENTAL

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)

Biological: Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC) High Dose

Interventions

Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC) High Dose BIOLOGICAL

Biological/Vaccine: Allogenic embryonic stem cell-derived 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.

High Dose Group

Allogenic embryonic stem cell-derived A9 dopamine progenitor cell (A9-DPC) Low Dose BIOLOGICAL

Biological/Vaccine: Allogenic embryonic stem cell-derived 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.

Low Dose Group

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with Parkinson's disease based on UK PD Society Brain Bank criteria at the time of the screening visit
• Patient with Parkinson's disease at the age of 50 to 75 years old at the time of the screening visit
• Patient who was diagnosed with Parkinson' disease ≥ 5 years ago at the time of the screening visit
• Patient on a stable dose of medicine such as levodopa for ≥ 3 months before screening who has wearing off for ≥ 2 hours a day or freezing of gait responding to dopamine supplement or motor complications such as dyskinesia
• At least moderate impairment in activity of daily living (MDS-UPDRS part II ≥13)
• Patient on a stabile dose of standard treatment for Parkinson's disease (e.g., levodopa, dopamine agonists, MAO-B inhibitors, amantadine, anticholinergics, etc.) for ≥ 3 months before screening
• ≥ 40% in L-dopa responsiveness at the time of the screening visit
• Hoehn \& Yahr stage ≥ 3 during the off state and stage ≤ 3 during the on state at the time of the screening visit
• Decreased dopamine transporters as measured by FP-CIT PET at the time of the screening visit
• Able to undergo MRI
• Signed consent after being sufficiently informed of the study

You may not qualify if:

• Parkinson's disease dementia based on the Movement Disorders Society Task Force criteria
• Parkinsonism plus syndrome confirmed by PET and MRI images at the screening visit
• Patient that does not meet the criteria for Parkinson's disease dementia but has major visual hallucination
• Freezing of gait with no or ambiguous response to L-dopa
• Drug-induced parkinsonism
• History of uncontrolled seizure disorders within 24 weeks before screening
• Congenital developmental delay
• Past or current coagulation factor related diseases at the time of the screening visit
• Ongoing malignancies at the time of the screening visit or diagnosis of malignancies within the past 5 years
• Active tuberculosis, autoimmune disease, or decreased immunity at the time of the screening visit (treatment with chemotherapy within the past 3 years or white blood cell \[WBC\] \<3X10\^3 cells/µL)
• Patient diagnosed with diabetes mellitus
• Participation in another clinical trial within 4 weeks before screening
• History of treatment with cell therapy, except for blood transfusion, before study participation
• Side effects to anesthetics, contrast agents, etc.
• Past or current clinically significant diseases in the liver (including liver transplant), kidney, respiratory system, cardiovascular system, etc. or clinically significant laboratory test results at the time of the screening visit

Sponsors & Collaborators

• S.Biomedics Co., Ltd.: lead
• Yonsei University: collaborator

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, 03722, South Korea

Location

Related Publications (20)

• Rowland NC, Starr PA, Larson PS, Ostrem JL, Marks WJ Jr, Lim DA. Combining cell transplants or gene therapy with deep brain stimulation for Parkinson's disease. Mov Disord. 2015 Feb;30(2):190-5. doi: 10.1002/mds.26083. Epub 2014 Dec 17.

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• 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.

  PMID: 32402162 BACKGROUND

• Barker RA, Drouin-Ouellet J, Parmar M. Cell-based therapies for Parkinson disease-past insights and future potential. Nat Rev Neurol. 2015 Sep;11(9):492-503. doi: 10.1038/nrneurol.2015.123. Epub 2015 Aug 4.

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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.

  PMID: 28858313 BACKGROUND

• 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.

  PMID: 15872020 BACKGROUND

• Parmar M, Grealish S, Henchcliffe C. The future of stem cell therapies for Parkinson disease. Nat Rev Neurosci. 2020 Feb;21(2):103-115. doi: 10.1038/s41583-019-0257-7. Epub 2020 Jan 6.

  PMID: 31907406 BACKGROUND

• Barker RA; TRANSEURO consortium. Designing stem-cell-based dopamine cell replacement trials for Parkinson's disease. Nat Med. 2019 Jul;25(7):1045-1053. doi: 10.1038/s41591-019-0507-2. Epub 2019 Jul 1.

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• Baek MJ, Kim K, Park YH, Kim S. The Validity and Reliability of the Mini-Mental State Examination-2 for Detecting Mild Cognitive Impairment and Alzheimer's Disease in a Korean Population. PLoS One. 2016 Sep 26;11(9):e0163792. doi: 10.1371/journal.pone.0163792. eCollection 2016.

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• Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C, Giladi N, Holloway RG, Moore CG, Wenning GK, Yahr MD, Seidl L; Movement Disorder Society Task Force on Rating Scales for Parkinson's Disease. Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations. Mov Disord. 2004 Sep;19(9):1020-8. doi: 10.1002/mds.20213.

  PMID: 15372591 BACKGROUND

• Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. 1967. Neurology. 2001 Nov;57(10 Suppl 3):S11-26. No abstract available.

  PMID: 11775596 BACKGROUND

• Koh SB, Kim JW, Ma HI, Ahn TB, Cho JW, Lee PH, Chung SJ, Kim JS, Kwon DY, Baik JS. Validation of the korean-version of the nonmotor symptoms scale for Parkinson's disease. J Clin Neurol. 2012 Dec;8(4):276-83. doi: 10.3988/jcn.2012.8.4.276. Epub 2012 Dec 21.

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• Shulman LM, Armstrong M, Ellis T, Gruber-Baldini A, Horak F, Nieuwboer A, Parashos S, Post B, Rogers M, Siderowf A, Goetz CG, Schrag A, Stebbins GT, Martinez-Martin P. Disability Rating Scales in Parkinson's Disease: Critique and Recommendations. Mov Disord. 2016 Oct;31(10):1455-1465. doi: 10.1002/mds.26649.

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• Park HJ, Sohng KY, Kim S. Validation of the Korean version of the 39-Item Parkinson's Disease Questionnaire (PDQ-39). Asian Nurs Res (Korean Soc Nurs Sci). 2014 Mar;8(1):67-74. doi: 10.1016/j.anr.2014.02.004. Epub 2014 Mar 6.

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• Kefalopoulou Z, Politis M, Piccini P, Mencacci N, Bhatia K, Jahanshahi M, Widner H, Rehncrona S, Brundin P, Bjorklund A, Lindvall O, Limousin P, Quinn N, Foltynie T. Long-term clinical outcome of fetal cell transplantation for Parkinson disease: two case reports. JAMA Neurol. 2014 Jan;71(1):83-7. doi: 10.1001/jamaneurol.2013.4749.

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• Rasiah NP, Maheshwary R, Kwon CS, Bloomstein JD, Girgis F. Complications of Deep Brain Stimulation for Parkinson Disease and Relationship between Micro-electrode tracks and hemorrhage: Systematic Review and Meta-Analysis. World Neurosurg. 2023 Mar;171:e8-e23. doi: 10.1016/j.wneu.2022.10.034. Epub 2022 Oct 13.

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• Li W, Englund E, Widner H, Mattsson B, van Westen D, Latt J, Rehncrona S, Brundin P, Bjorklund A, Lindvall O, Li JY. Extensive graft-derived dopaminergic innervation is maintained 24 years after transplantation in the degenerating parkinsonian brain. Proc Natl Acad Sci U S A. 2016 Jun 7;113(23):6544-9. doi: 10.1073/pnas.1605245113. Epub 2016 May 2.

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• 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.

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Related Links

• Phase 1 Safety and Tolerability Study of MSK-DA01 Cell Therapy for Advanced Parkinson's Disease.

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Phil-hyu Lee, MD, Ph.D

  Yonsei Universitiy Health System, Severance Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 rule-based method

Study Record Dates

• First Submitted: April 9, 2023
• First Posted: June 2, 2023
• Study Start: May 9, 2023
• Primary Completion: December 10, 2025
• Study Completion: December 10, 2025
• Last Updated: April 13, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)