Multiple System Atrophy (MSA)
Conditions
Brief summary
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
This study will consist of a core part, an extension part, and an additional extension part. The purpose of the core part 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. The purpose of the extension part and the additional extension part is to evaluate 3 doses of ONO-2808 in MSA patients, including: 1) safety and tolerability and 2) changes in COAs and biomarkers considered to be related to the pharmacodynamics and potential efficacy of ONO-2808.
Interventions
DRUGONO-2808
Oral administration of ONO-2808 at low, middle or high doses once daily for 24 weeks in the core part, for a total of 80 weeks including the extension part, and for up to an additional 72 weeks in the additional extension part
DRUGPlacebo
Oral administration of placebo once daily for 24 weeks in the core part and for a total of 32 weeks including the extension part; Transition to low-dose of ONO-2808 for remainder of the extension part until week 80 and for up to an additional 72 weeks in the additional extension part
Sponsors
Ono Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. 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). 2. 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 3. Patients with an anticipated survival of at least 3 years in the opinion of the Investigator. 4. 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. 5. Ability to swallow oral medication and be willing to adhere to the study intervention regimen.
Exclusion criteria
1. Pregnant or lactating females. 2. 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). 3. 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. 4. Patients with documented liver diseases or cirrhosis. 5. 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). 6. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) | From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164) | 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. |
| Vital signs (blood pressure) | From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164) | Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. |
| Vital signs (pulse rate) | From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164) | Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. |
| Vital signs (temperature) | From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164) | Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. |
| Vital signs (respiratory rate) | From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164) | Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point. |
| 12-lead electrocardiograms (ECGs); parameters such as, but not limited to, heart rate, RR, PR, QRS, QT, and corrected QT intervals (QTcF) | From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164) | The number of patients with normal, abnormal not clinically significant and abnormal clinically significant of ECG results will be tabulated at each time point. |
| Clinically-significant abnormal physical examination findings | From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164) | 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. |
| Clinical laboratory abnormalities (hematology, clinical chemistry, and urinalysis) | From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164) | The number of patients with abnormal laboratory results at any time during the study will be tabulated. |
| Clinically-abnormal findings in the Columbia Suicide Severity Rating Scale (C-SSRS) | From screening up to follow-up for the core part, for the extension part, and for the additional extension part (up to Week 164) | Responses to the suicidality assessment scale (C-SSRS) will be listed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentration of ONO-2808 | Week 2, Week 8, Week 12, and Week 24 | Descriptive summary statistics will be calculated for ONO-2808 plasma concentrations, by dose level and time point. |
Countries
Japan, United States
Contacts
STUDY_DIRECTORProject Leader
Ono Pharmaceutical Co., Ltd.
Outcome results
None listed