A Multicenter Study to Evaluate Safety, Tolerability, and Clinical Responses of DSP-1083 Into Subjects With Parkinson's Disease

A Multicenter, Sham-controlled, Randomized Study to Evaluate the Safety, Tolerability, and Clinical Responses Following Stereotactic Intracranial Implantation of DSP-1083 Into Subjects With Parkinson's Disease

The Goal of this study is to evaluate the safety, tolerability, and clinical responses following implantation of DSP-1083. Study enrolls both male and female patients in 2 cohorts. This study will be held in approximately 5-8 study sites in United States

Study Overview

• Status: Recruiting
• Conditions: Parkinson's Disease
• Intervention / Treatment: Combination product: DSP-1083 implantation; Procedure: Sham surgery treatment

Detailed Description

This is a multicenter first-in-human (FIH) study designed to evaluate the safety, tolerability, and clinical responses following implantation of dopaminergic progenitor cells derived from induced pluripotent stem cells (DSP-1083) compared with sham surgery. Safety is measured based on adverse events, changes in neuropsychiatric/cognition status, and serial neuroimaging (ie, engraftment status, graft expansion, rejection) over 104 weeks.

Cohort 1 sentinel subject (SS1) will undergo 2 unilateral surgical procedures separated by approximately 28 weeks, whereas SS2 and all subsequent subjects will undergo 1 bilateral surgical procedure.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • University of Kentucky Medical Center
      • Contact: Lynne Cagle; Phone Number: 859-218-5443; Email: Lynne.cagle@uky.edu
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • New York Presbyterian Hospital-Columbia University Medical Center
      • Contact: Natasha Desai; Phone Number: 347-882-4315; Email: Nd2528@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Men or women aged ≥ 40 and ≤ 72 years at the time of informed consent with a clinically established diagnosis of Parkinson's disease in accordance with the Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson's Disease.
2. Subject has a clinically established diagnosis of PD for ≥ 4 years.
3. Subject has suboptimal control of PD symptoms, with optimized oral antiparkinsonian medication regimen including levodopa/carbidopa monotherapy or levodopa/carbidopa plus antiparkinsonian medications, with stable dosing for ≥ 2months prior to screening.
4. Subject has a L-DOPA response of ≥ 30% without the influence of antiparkinsonian medications at Screening.
5. Subject has a Modified Hoehn and Yahr stage 3 - 4 in the Off state.
6. Subject has a pretreatment 18F-DOPA PET scan consistent with PD.
7. Subject has both On and Off states as demonstrated by the MDS-UPDRS Part III/IV and the Hauser patient daily diary.
8. Subjects must meet the following race criteria: 2 of the up to 5 sentinel subjects will be of Asian race, defined as having at least 2 grandparents who are Japanese, Taiwanese, Korean, or Chinese. Subjects in Cohort 2 can be of any race.
9. Subject is approved by the Enrollment Authorization Eligibility Committee following review of all required information collected during Screening.

Exclusion Criteria:

1. Subject has atypical parkinsonian syndrome (eg, progressive supranuclear palsy [PSP], multiple system atrophy [MSA], dementia with Lewy bodies [DLB], corticobasal degeneration, Parkinson-plus syndrome, vascular parkinsonism, secondary parkinsonism, hereditary parkinsonism).
2. Subject has non-PD neurological symptoms or evidence of non-PD brain disease (eg, tumor, inflammation, active or history of vascular disorder, history of cerebral hemorrhage, Alzheimer's disease, or other neurodegenerative disorder) based on neuroimaging and/or medical history that would preclude study participation.
3. Subject has psychiatric symptoms, cognitive impairment, depression, dementia, or other behavioral disorder that would preclude study participation based on Investigator decision.
4. Subject has received previous striatal or other extrapyramidal system PD treatments, including deep-brain stimulation, central nervous system (CNS) ablation (eg, pallidotomy, thalamotomy), implanted cell, or gene therapy, and/or focused ultrasound therapy.
5. Subject has peak-dose dyskinesia of sufficient severity that precludes study participation, defined as any item score of ≥ 3 (moderate dyskinesia) on the UDysRS Part 1B (Patient Dyskinesia Questionnaire) AND/OR any item score of ≥ 2 (moderate dyskinesia) on Part 3 (Objective Evaluation of Dyskinesia Disability) Intensity Scale: Impairment. Subject has another type (eg, diphasic dyskinesia) or an unusual pattern of dyskinesia.
6. Subject has a history of, or concurrent abnormal immune function that may adversely affect the engraftment of the cell implants and use of adjunctive immunosuppressants.

7. The subject has the following clinical laboratory test results at Screening:

   • Neutrophil count < 2,000/μL.
   • Platelet count < 5.0 × 104/μL.
   • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 3.0 × upper limit of normal.
   • Total bilirubin > 1.5 × upper limit of normal.
   • Persistent estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2.
   • Poorly controlled blood glucose in diabetic subjects (glycosylated hemoglobin > 9.0%, or fasting serum glucose ≥ 200mg/dL).
8. Subject has any disorder that would contraindicate general anesthesia, conscious sedation or stereotactic surgery.
9. Subject has any clinically significant unstable medical condition or any clinically significant chronic disease that would pose a risk to the subject or that might confound the results of the study. In cases in which the impact of the condition upon risk to subject or study results is unclear, the Medical Monitor should be consulted.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DSP-1083; Implantation of DSP-1083 (2.7M viable cells per hemisphere; 5.4M total cell dose)	Combination product: DSP-1083 implantation; DSP-1083 subjects will receive 2.7M viable cells per hemisphere; 5.4M total cell dose as implants.
Sham Comparator: Sham Surgery; Sham surgery subjects will undergo a partial thickness burr hole surgical procedure on each side of the skull with no DSP-1083 administration.	Procedure: Sham surgery treatment; Sham surgery subjects will undergo a partial thickness burr hole surgical procedure on each side of the skull with no DSP-1083 administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Adverse Events.		Up to 104 weeks
Incidence of Serious Adverse Events (SAE).		Up to 104 weeks
Incidence and severity of Adverse Events of Special Interest (AESI).		Up to 104 weeks
Incidence and severity of Adverse Events leading to study discontinuation.		Up to 104 weeks
Change from baseline in cognition and neuropsychiatric status as assessed by Montreal Cognitive Assessment (MoCA).	The MoCA is a widely used, sensitive, validated screening test for detecting mild cognitive impairment and can also predict the presence of cognitive deterioration (ie, progression from mild cognitive impairment to dementia) in PD patients.	Up to 104 weeks
Change from baseline in cognition and neuropsychiatric status as assessed by Mattis Dementia Rating Scale (MDRS).	The MDRS has been utilized for early detection of dementia, differential diagnosis between Alzheimer's disease and other dementias. The 144-point scale is an aggregate score of 5 subscales: attention, initiation/perseveration (I/P), construction, conceptualization, and memory.The total score ranges from 0 to 144, with lower scores indicating greater cognitive impairment.	Up to 104 weeks
Change from baseline in Head Magnetic Resonance Imaging (MRI) (graft expansion/rejection) neuroimaging parameters.	Safety MRIs - are conducted to assess the safety of DSP-1083 including rejection, abnormal growth, and formation of mass lesions, which could indicate teratoma formation	Up to 104 weeks
Change from baseline in Fluorodopa (F-DOPA) uptake (graft function) neuroimaging parameters.	PET scans using F-DOPA will be performed at Screening and then post-surgery to follow the course of graft development and to provide a measure of dopaminergic nerve terminals in the striatum.	Up to 104 weeks
Frequency of subjects with suicidal ideation or suicidal behavior using the Columbia Suicide Severity Scale (C-SSRS).		Up to 104 weeks
Observed values and change from baseline in clinical laboratory tests.	Laboratory results at each time point will be summarized using descriptive statistics (mean, standard deviation (SD), median, minimum, and maximum) by treatment group.	Up to 104 weeks
Observed values and change from baseline in Heart Rate (HR).	12-lead ECG parameters ventricular HR at each time point will be summarized by treatment group. All ECG diagnostic findings will be summarized on the basis of incidence rates by treatment group.	Up to 104 weeks
Observed values and change from baseline in QT interval.	12-lead ECG parameters QT interval at each time point will be summarized by treatment group. All ECG diagnostic findings will be summarized on the basis of incidence rates by treatment group.	Up to 104 weeks
Observed values and change from baseline in PR interval.	12-lead ECG parameters PR interval at each time point will be summarized by treatment group. All ECG diagnostic findings will be summarized on the basis of incidence rates by treatment group.	Up to 104 weeks
Observed values and change from baseline in QRS duration.	12-lead ECG parameters QRS duration at each time point will be summarized by treatment group. All ECG diagnostic findings will be summarized on the basis of incidence rates by treatment group.	Up to 104 weeks
Observed values and change from baseline in RR interval.	12-lead ECG parameters RR interval at each time point will be summarized by treatment group. All ECG diagnostic findings will be summarized on the basis of incidence rates by treatment group.	Up to 104 weeks
Observed values and change from baseline in QTcF interval.	12-lead ECG parameters QTcF interval at each time point will be summarized by treatment group. All ECG diagnostic findings will be summarized on the basis of incidence rates by treatment group.	Up to 104 weeks
Observed values and change from baseline in body temperature.	Vital signs parameter body temperature will be summarized using descriptive statistics at each time point by treatment group.	Up to 104 weeks
Observed values and change from baseline in respiratory rate.	Vital signs parameter supine respiratory rate will be summarized using descriptive statistics at each time point by treatment group.	Up to 104 weeks
Observed values and change from baseline in pulse rate.	Vital signs parameter supine and standing pulse will be summarized using descriptive statistics at each time point by treatment group.	Up to 104 weeks
Observed values and change from baseline in Systolic Blood Pressure.	Vital signs parameter Systolic Blood Pressure will be summarized using descriptive statistics at each time point by treatment group.	Up to 104 weeks
Observed values and change from baseline in Diastolic Blood Pressure.	Vital signs parameter Diastolic Blood Pressure will be summarized using descriptive statistics at each time point by treatment group.	Up to 104 weeks

Collaborators and Investigators

• Sponsor: Sumitomo Pharma America, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2024
• Primary Completion (Estimated): December 15, 2030
• Study Completion (Estimated): December 15, 2030

Study Registration Dates

• First Submitted: November 19, 2024
• First Submitted That Met QC Criteria: December 20, 2024
• First Posted (Actual): December 31, 2024

Study Record Updates

• Last Update Posted (Actual): March 2, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• 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
• Other Study ID Numbers: DD201101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No