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Sponsor has decided to withdraw the study due to safety issue and re-initiate with a new clinical study
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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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This trial will the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA.
This is a randomized, double-blind, placebo-controlled phase II trial. This trial will be performed in two part: Main study and Ancillary study.
Main Study: Following a 4-week screening period, subjects will be stratified by MSA subtype (MSA-P, -C [MSA-Parkinsonian type, MSA-cerebellar ataxia]) and randomly assigned in a 1:1 ratio either to KM-819 or Placebo groups.
During a treatment period of 36 weeks, subjects will receive pills of either KM-819 or Placebo for oral administration every day from baseline visit. Following this, there will be a safety follow-up period at Week 40.
Ancillary Study: This ancillary study will provide additional information on the continuing efficacy and safety of KM-819. Subjects in either treatment group in the main study who complete the study are eligible to participate in a follow-up, all-subjects-on-treatment (KM-819), open-label ancillary study.
All subjects in the ancillary study will receive KM-819 for additional 36 weeks regardless of their treatment allocation during the main study. During a treatment period of 36 weeks, subjects will receive pills of KM-819 for oral administration every day from visit at Weeks 40.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Main Study: KM-819 | Experimental | Subjects will receive 400 mg of KM-819 orally from Week 0 to Week 36. |
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| Main Study: Placebo | Placebo Comparator | Subjects will receive visually identical placebo pills of KM-819 orally. |
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| Ancillary Study: KM-819 | Experimental | Subjects will receive 400 mg of KM-819 orally from Week 40 to Week 76. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KM-819 | Drug | Subjects will receive KM-819 400 mg orally daily. |
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| Measure | Description | Time Frame |
|---|---|---|
| Percentage change from baseline in putaminal [18F]FP-CIT (18F-FP-CIT Positron Emission Tomography for Correlating Motor and Cognitive Symptoms of Parkinson's Disease) binding | To evaluate the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA. The putaminal [18F]FP-CIT binding will allow quantification of MSA progression during 36 weeks. | From Baseline to Week 36 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in the Unified Multiple System Atrophy Rating Scale (UMSARS) scores (UMSARS I + II) | To evaluate the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA. The Unified Multiple System Atrophy Rating Scale (UMSARS) was developed to provide a surrogate measure of disease progression in multiple system atrophy. It is composed of four subscales: UMSARS-I (12 items) rates patient-reported functional disability (Historical Review), UMSARS-II (14 items) assesses motor impairment based on a clinical examination. Each item scores 0-4. UMSARS-I total score is 48 and UMSARS-II total score is 56. Higher scores on the UMSARS indicate greater disability. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Chong Sik Lee | PI | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHA Bundang Medical Center, CHA University | Seongnam-si | Gyeonggi-do | 13497 | South Korea |
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| ID | Term |
|---|---|
| D019578 | Multiple System Atrophy |
| D019636 | Neurodegenerative Diseases |
| D054969 | Primary Dysautonomias |
| ID | Term |
|---|---|
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
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| ID | Term |
|---|---|
| C000634265 | KM-819 |
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| Placebo | Drug | Subjects will receive Placebo orally daily. |
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| From Baseline to Week 36 |
| Change from baseline in the UMSARS I scores | To evaluate the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA. The Unified Multiple System Atrophy Rating Scale (UMSARS) was developed to provide a surrogate measure of disease progression in multiple system atrophy. It is composed of four subscales: UMSARS-I (12 items) rates patient-reported functional disability (Historical Review), UMSARS-II (14 items) assesses motor impairment based on a clinical examination. Each item scores 0-4. UMSARS-I total score is 48. Higher scores on the UMSARS indicate greater disability. | From Baseline to Week 36 |
| Change from baseline in the UMSARS II scores | To evaluate the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA. The Unified Multiple System Atrophy Rating Scale (UMSARS) was developed to provide a surrogate measure of disease progression in multiple system atrophy. It is composed of four subscales: UMSARS-I (12 items) rates patient-reported functional disability (Historical Review), UMSARS-II (14 items) assesses motor impairment based on a clinical examination. Each item scores 0-4. UMSARS-II total score is 56. Higher scores on the UMSARS indicate greater disability. | From Baseline to Week 36 |
| Percentage change from baseline in putaminal glucose metabolism | To evaluate the efficacy of KM-819 compared to placebo for slowing the putaminal of MSA, as measured by [18F]FDG PET (fluorodeoxyglucose (FDG)-positron emission tomography (PET)). | From Baseline to Week 36 |
| Percentage change from baseline in cerebellar glucose metabolism | To further evaluate the efficacy of KM-819 compared to placebo for slowing the cerebellar progression of MSA, as measured by [18F]FDG PET. | From Baseline to Week 36 |
| Change from baseline in the Unified Parkinson Disease Rating Scale (UPDRS) III score | To evaluate the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA, measured by clinical scales. The UPDRS is the most widely applied rating instrument for PD. The Total UPDRS III scale includes 18 items. Each item scores 0-4. UPDRS III total score is 72. The highest score refers to the most severe level of disability due to Parkinson's disease. | From Baseline to Week 36 |
| Change from baseline in the Scale for the Assessment and Rating of Ataxia (SARA) score | To evaluate the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA, measured by clinical scales. The SARA is a tool for assessing ataxia. It has eight categories with an accumulative scores ranging from 0 (no ataxia) to 40 (most severe ataxia). The eight categories were: Gait (0-8 score); Stance (0-6 score); Sitting (0-4 score); Speech disturbance (0-6 score); Finger chase(0-4 score); Nose-finger test (0-4 score); Fast alternating hand movements (0-4 score); Heel-shin slide (0-4 score). Mild dependence: 5.5 or lower, Moderate dependence: 14.25 or lower, Maximal dependence: 23 of higher. | From Baseline to Week 36 |
| Change from baseline in the Montreal Cognitive Assessment (MoCA) score | To evaluate the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA, measured by clinical scales. MoCA can be used to detect dementia in a clinical setting. A total score of 30 with over 26 is normal. The lower score refers the severe cognitive impairment. | From Baseline to Week 36 |
| Change from baseline in the Beck's Depression Inventory (BDI-II) score | To evaluate the efficacy of KM-819 compared to placebo in subjects with MSA for slowing the progression of MSA, measured by clinical scales. The BDI-II is scored by summing the ratings for the 21 items. Each item is rated on a 4-point scale ranging from 0 to 3. The maximum total score is 63. Measures of 0-13: Minimal, 14-19: Mild, 20-28: Moderate, 29-63: Severe. | From Baseline to Week 36 |
| Number of subjects with adverse events (AEs) and serious AEs (SAEs) | To evaluate the safety of KM-819 in subjects with MSA. | From Screening (Day -4) to Week 40 |
| Maximum observed concentration (Cmax) | To describe the pharmacokinetics parameter (Cmax) of KM-819 using sparse PK sampling. | From Baseline to Week 36 |
| Area under the concentration-time curve (AUC) | To describe the pharmacokinetics parameter (AUC) of KM-819 using sparse PK sampling. | From Baseline to Week 36 |
| Time of maximum observed concentration (Tmax) | To describe the pharmacokinetics parameter (Tmax) of KM-819 using sparse PK sampling. | From Baseline to Week 36 |
| D002493 | Central Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |