A Phase 2 Study of ONO-2808 in Patients With Multiple System Atrophy (NCT05923866) — USA Trial Details

Condition(s) studied

Multiple System Atrophy (MSA)

Investigational drug(s) / intervention(s)

ONO-2808Placebo

ONO-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

Placebo: 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

Study 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.

Eligibility

Sex

ALL

Min age

30 Years

Max age

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.

Primary outcome measure(s)

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.

Trial sites (35)

Facility	City	Region
The Parkinson's Movement and Disorder Institute	Fountain Valley	California
University of Southern California	Los Angeles	California
David Geffen School of Medicine at UCLA	Los Angeles	California
Stanford University School of Medicine	Palo Alto	California
CenExel Rocky Mountain Clinical Research	Englewood	Colorado
Yale School of Medicine - Yale Church Street Research Unit (CRSU)	New Haven	Connecticut
Parkinson's Disease and Movement Disorders Center of Boca Raton	Boca Raton	Florida
Norman Fixel Institute for Neurological Diseases - University of Florida	Gainesville	Florida
Mayo Clinic in Florida	Jacksonville	Florida
University of Miami Miller School of Medicine	Miami	Florida
Emory University School of Medicine	Atlanta	Georgia
University of Kansas Medical Center Research Institute	Kansas City	Kansas
Massachusetts General Hospital	Boston	Massachusetts
Brigham and Women's Hospital	Boston	Massachusetts
University of Michigan School of Medicine	Ann Arbor	Michigan
Quest Research Institute	Farmington Hills	Michigan
Mayo Clinic - Rochester	Rochester	Minnesota
University of Nebraska Medical Center	Omaha	Nebraska
NYU Langone Health - NYU Dysautonomia Center	New York	New York
Icahn School of Medicine at Mount Sinai	New York	New York
Columbia University	New York	New York
University of Cincinnati College of Medicine	Cincinnati	Ohio
Cleveland Clinic	Cleveland	Ohio
Ohio State University	Columbus	Ohio
Penn State University - Milton S. Hershey Medical Center	Hershey	Pennsylvania
The University of Pennsylvania - Pennsylvania Hospital	Philadelphia	Pennsylvania
UT Southwestern Medical Center	Dallas	Texas
Virginia Commonwealth University Medical Center	Richmond	Virginia
Evergreen Health	Kirkland	Washington
Swedish Neuroscience Institute, Movement Disorders Clinic	Seattle	Washington
Fujita Health University Hospital	Toyoake	Aichi-ken
National Hospital Organization Utano National Hospital	Kyoto	Kyoto
National Hospital Organization Sendai Nishitaga Hospital	Sendai	Miyagi
National Hospital Organization Osaka Toneyama Medical Center	Toyonaka	Osaka
Tokyo Metropolitan Neurological Hospital	Fuchū	Tokyo

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