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

NCT05923866 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: ONO-2808-03jRCT2041230153
• Study Type: interventional
• Target: 92
• Locations: 2 countries
• Sites: 35

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.

Conditions

Multiple System Atrophy (MSA)

Outcome Measures

Primary Outcomes (9)

• 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 for the core part and for the extension part (up to Week 92)

• 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 for the core part and for the extension part (up to Week 92)

• 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 for the core part and for the extension part (up to Week 92)

• 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 for the core part and for the extension part (up to Week 92)

• 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 for the core part and for the extension part (up to Week 92)

• 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 for the core part and for the extension part (up to Week 92)

• 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 for the core part and for the extension part (up to Week 92)

• 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 for the core part and for the extension part (up to Week 92)

• 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 for the core part and for the extension part (up to Week 92)

Secondary Outcomes (2)

• Plasma concentration of ONO-2808

  Week 2, Week 8, Week 12, and Week 24

• ONO-2808 concentration in cerebrospinal fluid (CSF)

  Week 24

Study Arms (2)

ONO-2808 Arm

EXPERIMENTAL

Drug: ONO-2808

Placebo Arm

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ONO-2808 DRUG

Oral administration of ONO-2808 at low, middle or high doses once a daily for 24 weeks in the core part and 80 weeks total including the extension part

ONO-2808 Arm

Placebo DRUG

Oral administration of placebo once a daily for 24 weeks in the core part and 32 weeks total including the extension part; Transition to low-dose of ONO-2808 for remainder of the extension part until week 80

Placebo Arm

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ono Pharmaceutical Co. Ltd: lead

Study Sites (35)

The Parkinson's Movement and Disorder Institute

Fountain Valley, California, 92708, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94304, United States

Location

CenExel Rocky Mountain Clinical Research

Englewood, Colorado, 80113, United States

Location

Yale School of Medicine - Yale Church Street Research Unit (CRSU)

New Haven, Connecticut, 06519, United States

Location

Parkinson's Disease and Movement Disorders Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

Norman Fixel Institute for Neurological Diseases - University of Florida

Gainesville, Florida, 32608, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30329, United States

Location

University of Kansas Medical Center Research Institute

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Michigan School of Medicine

Ann Arbor, Michigan, 48109, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

NYU Langone Health - NYU Dysautonomia Center

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10019, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Cincinnati College of Medicine

Cincinnati, Ohio, 45219, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43201, United States

Location

Penn State University - Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

The University of Pennsylvania - Pennsylvania Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Virginia Commonwealth University Medical Center

Richmond, Virginia, 23298, United States

Location

Evergreen Health

Kirkland, Washington, 98034, United States

Location

Swedish Neuroscience Institute, Movement Disorders Clinic

Seattle, Washington, 98122, United States

Location

Fujita Health University Hospital

Toyoake, Aichi-ken, Japan

Location

National Hospital Organization Utano National Hospital

Kyoto, Kyoto, Japan

Location

National Hospital Organization Sendai Nishitaga Hospital

Sendai, Miyagi, Japan

Location

National Hospital Organization Osaka Toneyama Medical Center

Toyonaka, Osaka, Japan

Location

Tokyo Metropolitan Neurological Hospital

Fuchū, Tokyo, Japan

Location

MeSH Terms

Conditions

Multiple System Atrophy

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Project Leader

  Ono Pharmaceutical Co. Ltd

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: June 28, 2023
• Study Start: September 22, 2023
• Primary Completion: September 15, 2025
• Study Completion (Estimated): January 1, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

JP (5); US (30)