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

Multiple System Atrophy (MSA) Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05923866
• Other study ID #: ONO-2808-03
• Status: Recruiting
• Phase: Phase 2
• Start date: September 22, 2023
• Est. completion date: August 31, 2025

Study information

• Verified date: May 2024
• Source: Ono Pharmaceutical Co. Ltd
• Contact: Ono Pharma USA, Inc.
• Email: clinical_trial[@]ono-pharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: August 31, 2025
• Est. primary completion date: August 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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 Unified Multiple System Atrophy Rating Scale (UMSARS) 1 total score (excluding item 1.11 sexual function) of = 17.

4. Patients with an anticipated survival of at least 3 years in the opinion of the Investigator.

5. 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.

6. 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.

Related Conditions & MeSH terms

• Atrophy
• Multiple System Atrophy
• Multiple System Atrophy (MSA)
• Shy-Drager Syndrome

Intervention

Drug:
• ONO-2808
Oral administration of ONO-2808 at low, middle or high doses once a daily for 24 weeks
• Placebo
Oral administration of placebo once a daily for 24 weeks

Locations

Country	Name	City	State
United States	Parkinson's Disease and Movement Disorders Center	Boca Raton	Florida
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	UT Southwestern Medical Center	Dallas	Texas
United States	CenExel Rocky Mountain Clinical Research	Englewood	Colorado
United States	Quest Research Institute	Farmington Hills	Michigan
United States	The Parkinson's Movement and Disorder Institute	Fountain Valley	California
United States	Norman Fixel Institute for Neurological Diseases - University of Florida	Gainesville	Florida
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	University of Kansas Medical Center Research Institute	Kansas City	Kansas
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Yale School of Medicine - Yale Church Street Research Unit (CRSU)	New Haven	Connecticut
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	The University of Pennsylvania - Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	Parkinson's Disease Treatment Center of SW Florida	Port Charlotte	Florida
United States	Swedish Neuroscience Institute, Movement Disorders Clinic	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Ono Pharmaceutical Co. Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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)
Primary	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	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
Secondary	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