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
概览
- 阶段
- 1 期
- 干预措施
- DSP-1083 implantation
- 疾病 / 适应症
- Parkinson's Disease
- 发起方
- Sumitomo Pharma America, Inc.
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Incidence and severity of Adverse Events.
- 状态
- 招募中
- 最后更新
- 2个月前
概览
简要总结
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
详细描述
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.
研究者
入排标准
入选标准
- •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.
- •Subject has a clinically established diagnosis of PD for ≥ 4 years.
- •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.
- •Subject has a L-DOPA response of ≥ 30% without the influence of antiparkinsonian medications at Screening.
- •Subject has a Modified Hoehn and Yahr stage 3 - 4 in the Off state.
- •Subject has a pretreatment 18F-DOPA PET scan consistent with PD.
- •Subject has both On and Off states as demonstrated by the MDS-UPDRS Part III/IV and the Hauser patient daily diary.
- •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.
- •Subject is approved by the Enrollment Authorization Eligibility Committee following review of all required information collected during Screening.
排除标准
- •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).
- •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.
- •Subject has psychiatric symptoms, cognitive impairment, depression, dementia, or other behavioral disorder that would preclude study participation based on Investigator decision.
- •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.
- •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.
- •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.
- •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.
研究组 & 干预措施
DSP-1083
Implantation of DSP-1083 (2.7M viable cells per hemisphere; 5.4M total cell dose)
干预措施: DSP-1083 implantation
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.
干预措施: Sham surgery treatment
结局指标
主要结局
Incidence and severity of Adverse Events.
时间窗: Up to 104 weeks
Incidence of Serious Adverse Events (SAE).
时间窗: Up to 104 weeks
Incidence and severity of Adverse Events of Special Interest (AESI).
时间窗: Up to 104 weeks
Incidence and severity of Adverse Events leading to study discontinuation.
时间窗: Up to 104 weeks
Change from baseline in cognition and neuropsychiatric status as assessed by Montreal Cognitive Assessment (MoCA).
时间窗: Up to 104 weeks
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.
Change from baseline in cognition and neuropsychiatric status as assessed by Mattis Dementia Rating Scale (MDRS).
时间窗: Up to 104 weeks
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.
Change from baseline in Head Magnetic Resonance Imaging (MRI) (graft expansion/rejection) neuroimaging parameters.
时间窗: Up to 104 weeks
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
Change from baseline in Fluorodopa (F-DOPA) uptake (graft function) neuroimaging parameters.
时间窗: Up to 104 weeks
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.
Frequency of subjects with suicidal ideation or suicidal behavior using the Columbia Suicide Severity Scale (C-SSRS).
时间窗: Up to 104 weeks
Observed values and change from baseline in clinical laboratory tests.
时间窗: Up to 104 weeks
Laboratory results at each time point will be summarized using descriptive statistics (mean, standard deviation (SD), median, minimum, and maximum) by treatment group.
Observed values and change from baseline in Heart Rate (HR).
时间窗: Up to 104 weeks
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.
Observed values and change from baseline in QT interval.
时间窗: Up to 104 weeks
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.
Observed values and change from baseline in PR interval.
时间窗: Up to 104 weeks
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.
Observed values and change from baseline in QRS duration.
时间窗: Up to 104 weeks
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.
Observed values and change from baseline in RR interval.
时间窗: Up to 104 weeks
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.
Observed values and change from baseline in QTcF interval.
时间窗: Up to 104 weeks
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.
Observed values and change from baseline in body temperature.
时间窗: Up to 104 weeks
Vital signs parameter body temperature will be summarized using descriptive statistics at each time point by treatment group.
Observed values and change from baseline in respiratory rate.
时间窗: Up to 104 weeks
Vital signs parameter supine respiratory rate will be summarized using descriptive statistics at each time point by treatment group.
Observed values and change from baseline in pulse rate.
时间窗: Up to 104 weeks
Vital signs parameter supine and standing pulse will be summarized using descriptive statistics at each time point by treatment group.
Observed values and change from baseline in Systolic Blood Pressure.
时间窗: Up to 104 weeks
Vital signs parameter Systolic Blood Pressure will be summarized using descriptive statistics at each time point by treatment group.
Observed values and change from baseline in Diastolic Blood Pressure.
时间窗: Up to 104 weeks
Vital signs parameter Diastolic Blood Pressure will be summarized using descriptive statistics at each time point by treatment group.