Transplantation of Human iPS Cell-derived Dopaminergic Progenitors (CT1-DAP001) for Parkinson's Disease (Phase I/II) (CT1-DAP001)

An Investigator-initiated Clinical Trial of Safety and Efficacy of Transplantation of Human Induced Pluripotent Stem Cell-derived Dopaminergic Progenitors (CT1-DAP001) for Parkinson's Disease (Phase I/II)

To evaluate the safety and efficacy of transplantation of human induced pluripotent stem cell-derived dopaminergic progenitors, CT1-DAP001, into the corpus striatum in patients with Parkinson's disease

Study Overview

• Status: Recruiting
• Conditions: PD - Parkinson's Disease
• Intervention / Treatment: Combination product: Human induced pluripotent stem cell-derived dopaminergic progenitors (CT1-DAP001)

Detailed Description

Single-center, open-label, uncontrolled. The primary objective of this study is to evaluate the safety of CT1-DAP001 in subjects with Parkinson's disease by determining the incidence and severity of adverse events, especially graft expansion, after transplantation into the corpus striatum. Other objectives are to evaluate the efficacy of CT1-DAP001 through the assessment of Parkinson's disease symptoms and clinical severity or progression.

• Study Type: Interventional
• Enrollment (Estimated): 7
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Donna Brusch; Phone Number: (760) 505-6649; Email: dbrusch@health.ucsd.edu
• Study Contact Backup: Name: Christian Fulinara; Phone Number: (858) 2494020; Email: chfulinara@health.ucsd.edu

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • University of California, San Diego
      • Principal Investigator: Joseph Ciacci, MD
      • Contact: Christian P Fulinara; Phone Number: 858-249-3038; Email: chfulinara@health.ucsd.edu
      • Contact: Donna Brusch; Phone Number: 760-505-6649; Email: dbrusch@health.ucsd.edu
      • Sub-Investigator: Sharona Ben-Haim, MD
      • Sub-Investigator: Stephanie Lessig, MD
      • Sub-Investigator: Forseth Kiefer, MD
      • Sub-Investigator: Marsala Martin, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. The subject has a diagnosis of PD (clinically established or clinically probable) in accordance with the MDS Clinical Diagnostic Criteria for Parkinson's Disease (2015).
2. The subject has an inadequate response to drug treatments.
3. The subject is ≥ 40 years and ≤ 75 years of age at the time of informed consent.
4. The subject has had PD for at least 5 years.
5. The subject has both ON and OFF (as demonstrated by the MDS-UPDRS Part III and a symptom diary).
6. The subject does not have a debilitating dyskinesia score greater than or equal to 3 on the MDS-UPDRS.
7. The subject is in stage 2 or higher on the Hoehn and Yahr scale at OFF time.
8. The subject is in stage 3 or lower on the Hoehn and Yahr scale at ON time.
9. The subject has an L-dopa response of 30% or more without influence of antiparkinsonian drugs.

10. The subject has the following organ functions as determined by laboratory tests at Screening visit:

    1. Neutrophil count ≥ 2,000/μL
    2. Platelet count ≥ 5.0 × 104/μL
    3. AST, ALT ≤ 3.0 × upper limit of normal
    4. Total bilirubin ≤ 1.5 × upper limit of normal
    5. eGFR ≥ 60 mL/min/1.73 m2 (As part of Creatinine testing, an estimated glomerular filtration rate (mL/min/1.73 m2)will be calculated based on the CKD-EPI 2021 equation)
11. The subject is willing to avoid pregnancy using abstinence, highly effective means of birth control, surgical sterility, or menopause.
12. The subject is willing to comply with the protocol-required assessments.
13. The subject provides written informed consent to participate in the study. If the subject cannot sign due to physical constraints, verbal consent may be provided with signature of a Legally Authorized Representative.

Exclusion Criteria:

1. The subject has an abnormal brain MRI suggestive of brain pathology other than Parkinson's disease.
2. Atypical parkinsonism (Parkinsonism-Plus syndrome, secondary parkinsonism, hereditary parkinsonism).
3. The subject has clinical indication or diagnosis of abnormal immune function.
4. The subject has been diagnosed with a major neurocognitive disorder such as dementia, or is high risk for this.
5. The subject has bleeding tendency or abnormal coagulation function as evidenced by platelets <50 or PT/PTT > 1.5x normal.
6. The subject is HBs antigen-positive, or HBs antibody- or HBc antibody-positive with evidence of HBV-DNA.
7. The subject is anti-HIV antibody positive.
8. The subject is anti-HTLV-1 antibody-positive.
9. The subject has active infection such as hepatitis C or syphilis (STS/TPHA).
10. The subject has hypersensitivity or contraindication to tacrolimus, concomitant drugs (e.g., levodopa, carbidopa, MRI contrast), and/or their components.
11. Contraindications to general anesthesia as evaluated by subject matter experts.
12. The subject has a serious allergy to a component (e.g., gentamicin, component of bovine origin, or component of porcine origin) used in the preparation of the study product.

13. The subject has any of the following conditions/diseases concurrently:

    1. Malignant neoplasm
    2. Epilepsy
    3. Psychiatric disease (e.g., uncontrolled anxiety or depression, bipolar disorder, schizophrenia)
    4. Diabetes mellitus with poorly controlled blood glucose (glycosylated hemoglobin > 9.0%, or fasting plasma glucose (FPG) ≥ 200 mg/dL (11.1 mmol/L).
    5. Other serious concurrent diseases (e.g., cerebrovascular disorder, heart disease, chronic respiratory disease, inadequately controlled hypertension) as determined by the investigator.

14. The subject has a history of any of the following:

    1. Prior malignancy < 5 years prior to Screening. Patients who had prior malignancies within 5 years and in complete remission with expected survival of more than 5 years are not excluded
    2. Epilepsy
    3. Cerebral hemorrhage or stroke
    4. Psychiatric disease (e.g., uncontrolled anxiety or depression, bipolar disorder, schizophrenia)
    5. Congenital long QT syndrome
    6. Pallidotomy, thalamotomy, or Deep Brain Stimulation
15. The subject is pregnant or lactating or does not agree to avoid pregnancy throughout the study.
16. The subject has undergone transplantation of human iPSC-derived dopaminergic progenitors.
17. The subject, in the opinion of the investigator or sub investigator, is not appropriate to conduct the study safely.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Single-center, open-label, uncontrolled; To evaluate the safety and efficacy of transplantation of human induced pluripotent stem cell-derived dopaminergic progenitors, CT1-DAP001, into the corpus striatum in patients with Parkinson's disease

Combination product: Human induced pluripotent stem cell-derived dopaminergic progenitors (CT1-DAP001); Investigational PET agents will be synthesized at UCSD and administered to subjects according to the local institutional guidelines. IND applications for these agents are linked with the IND application for the study product, CT1-DAP001. The IND applications for the PET radiopharmaceuticals contains the manufacturing method, specifications, quality testing, clinical usage, and safety and efficacy information for individual PET agents. Investigational Cell Injector Suniviion needle: The investigational instrument will be used to administer dopaminergic progenitors into the putamen. After aspirating cells, the instrument will be attached to a Leksell stereotactic frame to administer the cells into the brain.; Other Names: Investigational imaging - FDOPA & FEPPA; Investigational device - Sunovion needle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACCEPTABILITY	Assessed by presence or absence of graft expansion (> 3 cm3) in the brain at 24 months after transplantation	24 months
SAFETY	Incidence and severity of treatment emergent adverse events assessed by graft expansion and size in the corpus striatum.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QUALITY OF LIFE	Assessed by dyskinesia score, measured as the change in dyskinesia score from Baseline to each post-transplantation time point.	24 months
ACCURACY	Assessed by FDOPA (MRI) of tissue expansion The expansion on MRI will be assessed at each time point of measurement; day before transplantation,; immediately after transplantation,; day after transplantation,; 4 weeks, 12 weeks, 6 months, 18 months, (if clinically indicated); 12 months, 24 months after transplantation	24 months
MDS-UPDRS Part III totalscore (at OFF time)	This endpoint is defined as the change in UPDRS Part III score at OFF time from Baseline to each post-transplantation time point. The efficacy will be assessed based on MDS-UPDRS Part III total score at OFF time at 24 months after cell transplantation.; Excellent response defined as a decrease of ≥ 5; Good response defined as a decrease of 0 to 4	24 months
MDS-UPDRS Part III totalscore (at ON time)	This endpoint is defined as the change in UPDRS Part III score at ON time from Baseline to each post-transplantation time point.	24 months
Average daily ON duration (with or without dyskinesia) and OFF duration	This endpoint is defined as the change in daily ON duration (with or without dyskinesia) or OFF duration from Baseline to each post-transplantation time point.	24 months
L-dopa equivalent dose	This endpoint is defined as the change in L-dopa equivalent dose from Baseline to 4 weeks, 12 weeks, 6 months, 12 months, 18 months, or 24 months after transplantation. Formula to convert to the L-dopa dose: L-dopa 100 mg = pramipexole salt 1 mg = ropinirole 5 mg = rotigotine 7.5 mg = bromocriptine 10 mg = pergolide 1 mg = cabergoline 1.5 mg = selegiline 10 mg = amantadine 100 mg = apomorphine 10 mg	24 months

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Sumitomo Pharma Co., Ltd.; Kyoto University; Sumitomo Pharma America, Inc.; CiRA Foundation
• Investigators: Principal Investigator: Joseph Ciacci, MD, University of California, San Diego

Publications and helpful links

Helpful Links

• Parkinson's disease and related disorders (3) Parkinson's disease
• Pre-clinical study of induced pluripotent stem cell- derived dopaminergic progenitor cells for Parkinson's Disease

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2024
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 27, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: MRI; Neurodegenerative Disease; Parkinson's Disease; Brain Disease; CNS; PD; Movement Disorder; Dyskinesia; Ataxia; FDOPA; Central Nervous System Disease; Dopaminergic; Corpus striatum
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Protective Agents; Cardiotonic Agents; Dopamine Agents; Sympathomimetics; Dopamine; Dopamine Agonists
• Other Study ID Numbers: 808955

Drug and device information, study documents

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