Clinical trial NCT05923866: A Phase 2 Study of ONO-2808 in Patients With Multiple System Atrophy
Official title: A Phase 2, Double-blind, Placebo-controlled, Parallel-group Study Followed by an Open-label, Parallel Group Extension Part to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Potential Efficacy of Multiple Doses of ONO-2808 in Patients With Multiple System Atrophy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Multiple System Atrophy (MSA)
Lead sponsor: Ono Pharmaceutical Co. Ltd
Sponsor class: INDUSTRY
First posted: 2023-06-28
Enrollment: 92
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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: 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.

Eligibility criteria: 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 outcomes:
measure: Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
timeFrame: From screening up to follow-up (Week 28)
measure: Vital signs (blood pressure)
timeFrame: From screening up to follow-up (Week 28)
measure: Vital signs (pulse rate)
timeFrame: From screening up to follow-up (Week 28)
measure: Vital signs (temperature)
timeFrame: From screening up to follow-up (Week 28)
measure: Vital signs (respiratory rate)
timeFrame: From screening up to follow-up (Week 28)
measure: 12-lead electrocardiograms (ECGs); parameters such as, but not limited to, heart rate, RR, PR, QRS, QT, and corrected QT intervals (QTcF)
timeFrame: From screening up to follow-up (Week 28)
measure: Clinically-significant abnormal physical examination findings
timeFrame: From screening up to follow-up (Week 28)
measure: Clinical laboratory abnormalities (hematology, clinical chemistry, and urinalysis)
timeFrame: From screening up to follow-up (Week 28)
measure: Clinically-abnormal findings in the Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: From screening up to follow-up (Week 28)
Secondary outcomes:
measure: Plasma concentration of ONO-2808
timeFrame: Week 2, Week 8, Week 12, and Week 24
measure: ONO-2808 concentration in cerebrospinal fluid (CSF)
timeFrame: Week 24
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: The Parkinson's Movement and Disorder Institute
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: Englewood
country: United States
facility: CenExel Rocky Mountain Clinical Research
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine - Yale Church Street Research Unit (CRSU)
state: Connecticut
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorders Center of Boca Raton
state: Florida
city: Gainesville
country: United States
facility: Norman Fixel Institute for Neurological Diseases - University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory University School of Medicine
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center Research Institute
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan School of Medicine
state: Michigan
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: New York
country: United States
facility: NYU Langone Health - NYU Dysautonomia Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati College of Medicine
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Hershey
country: United States
facility: Penn State University - Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: The University of Pennsylvania - Pennsylvania Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
city: Kirkland
country: United States
facility: Evergreen Health
state: Washington
city: Seattle
country: United States
facility: Swedish Neuroscience Institute, Movement Disorders Clinic
state: Washington
city: Toyoake
country: Japan
facility: Fujita Health University Hospital
state: Aichi
city: Sendai
country: Japan
facility: National Hospital Organization Sendai Nishitaga Hospital
state: Miyagi
city: Toyonaka
country: Japan
facility: National Hospital Organization Osaka Toneyama Medical Center
state: Osaka
city: Fuchū
country: Japan
facility: Tokyo Metropolitan Neurological Hospital
state: Tokyo
city: Kyoto
country: Japan
facility: National Hospital Organization Utano National Hospital
Study officials:
affiliation: Ono Pharmaceutical Co. Ltd
name: Project Leader
role: STUDY_DIRECTOR
References: