A Phase 2 Study of ONO-2808 in Patients With Multiple System Atrophy

Study Overview
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Brief Summary
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This is a Phase 2, double-blind, parallel-group, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of multiple doses of ONO-2808 in patients with MSA. This is the first study of ONO-2808 in patients with MSA.

Detailed Description
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The purpose of the study is to evaluate 3 doses of ONO-2808 compared to placebo in MSA patients, including: 1) safety and tolerability, 2) pharmacokinetics, and 3) changes in clinical outcome assessments (COA) and biomarkers considered to be related to the pharmacodynamics and potential efficacy of ONO-2808.

Official Title
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A Phase 2, Double-blind, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Potential Efficacy of Multiple Doses of ONO-2808 in Patients With Multiple System Atrophy (MSA)

Conditions
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Multiple System Atrophy (MSA)

Intervention / Treatment
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* Drug: ONO-2808
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male patients with a diagnosis of clinically-established or clinically-probable MSA according to the novel Movement Disorder Society (MDS) criteria for MSA diagnosis (2022), including patients with MSA of either subtype (MSA-P or MSA-C). Patients at the early stages of the disease, defined as a maximum of 5 years since the onset of one of the following symptoms associated with MSA: Parkinsonism Ataxia Orthostatic hypotension and/or urinary dysfunction Patients with an Unified Multiple System Atrophy Rating Scale (UMSARS) 1 total score (excluding item 1.11 sexual function) of ≤ 17. Patients with an anticipated survival of at least 3 years in the opinion of the Investigator. Patients who are able to ambulate without the assistance of another person, defined as the ability to take at least 10 steps and then to turn around and walk at least another 10 steps. Use of assistive devices (e.g., walker or cane) is allowed. Ability to swallow oral medication and be willing to adhere to the study intervention regimen. Exclusion Criteria: Pregnant or lactating females. Patients with a clinically-significant or unstable medical or surgical condition other than MSA that, in the opinion of the Investigator, might preclude safe completion of the study or might affect the results of the study (e.g., pulmonary, cardiovascular [including bradyarrhythmia], macular edema, and significant renal or hepatic dysfunction). Neurological diseases/disorders other than MSA, such as Parkinson's disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, spinocerebellar ataxia, spastic paraparesis, corticobasal degeneration, or vascular, normal pressure hydrocephalus, pharmacological, or post-encephalitic parkinsonism. Patients with documented liver diseases or cirrhosis. Positive results at Screening for active viral infections that include positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis B core antibody, and hepatitis C virus (HCV). Patients with suicide ideation according to the Investigator's clinical judgment per the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening or who have made a suicide attempt in the 6 months before Screening.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ONO-2808 Arm<br> | Drug: ONO-2808<br>* Oral administration of ONO-2808 at low, middle or high doses once a daily for 24 weeks<br>|
| Placebo Comparator: Placebo Arm<br> | Drug: Placebo<br>* Oral administration of placebo once a daily for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) | Incidence of TEAEs, drug-related TEAEs, TEAEs resulting in study treatment discontinuation, TESAEs, and drug-related TESAEs will be tabulated by system organ class (SOC), preferred term (PT), and severity. | From screening up to follow-up (Week 28) | 
| Vital signs (blood pressure) | Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. | From screening up to follow-up (Week 28) | 
| Vital signs (pulse rate) | Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. | From screening up to follow-up (Week 28) | 
| Vital signs (temperature) | Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. | From screening up to follow-up (Week 28) | 
| Vital signs (respiratory rate) | Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. | From screening up to follow-up (Week 28) | 
| 12-lead electrocardiograms (ECGs); parameters such as, but not limited to, heart rate, RR, PR, QRS, QT, and corrected QT intervals (QTcF) | The number of patients with normal, abnormal not clinically significant and abnormal clinically significant of ECG results will be tabulated at each time point. | From screening up to follow-up (Week 28) | 
| Clinically-significant abnormal physical examination findings | The number of patients with normal, abnormal not clinically significant and abnormal clinically significant of physical examination results will be tabulated at each time point. | From screening up to follow-up (Week 28) | 
| Clinical laboratory abnormalities (hematology, clinical chemistry, and urinalysis) | The number of patients with abnormal laboratory results at any time during the study will be tabulated. | From screening up to follow-up (Week 28) | 
| Clinically-abnormal findings in the Columbia Suicide Severity Rating Scale (C-SSRS) | Responses to the suicidality assessment scale (C-SSRS) will be listed. | From screening up to follow-up (Week 28) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of ONO-2808 | Descriptive summary statistics will be calculated for ONO-2808 plasma concentrations, by dose level and time point. | Week 2, Week 8, Week 12, and Week 24 | 
| ONO-2808 concentration in cerebrospinal fluid (CSF) | Descriptive summary statistics will be calculated for ONO-2808 CSF concentrations, by dose level and time point. | Week 24 |