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

• ClinicalTrials.gov Identifier: NCT05923866
• Recruitment Status: Recruiting
• First Posted: June 28, 2023
• Last Update Posted: May 3, 2024
• Sponsor: Ono Pharmaceutical Co. Ltd
• Information provided by (Responsible Party): Ono Pharmaceutical Co. Ltd

Tracking Information

• First Submitted Date: June 7, 2023
• First Posted Date: June 28, 2023
• Last Update Posted Date: May 3, 2024
• Actual Study Start Date: September 22, 2023
• Estimated Primary Completion Date: August 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 15, 2023)

• Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs) [ Time Frame: From screening up to follow-up (Week 28) ]
  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) [ Time Frame: From screening up to follow-up (Week 28) ]
  Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
• Vital signs (pulse rate) [ Time Frame: From screening up to follow-up (Week 28) ]
  Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
• Vital signs (temperature) [ Time Frame: From screening up to follow-up (Week 28) ]
  Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
• Vital signs (respiratory rate) [ Time Frame: From screening up to follow-up (Week 28) ]
  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) [ Time Frame: From screening up to follow-up (Week 28) ]
  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 [ Time Frame: From screening up to follow-up (Week 28) ]
  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) [ Time Frame: From screening up to follow-up (Week 28) ]
  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) [ Time Frame: From screening up to follow-up (Week 28) ]
  Responses to the suicidality assessment scale (C-SSRS) will be listed.

Original Primary Outcome Measures (submitted: June 20, 2023)

• Incidence and severity of treatment-emergent AEs (TEAEs) and treatment-emergent SAEs (TESAEs) [ Time Frame: From screening up to follow-up (Week 28) ]
  Incidence of TEAEs, drug-related TEAEs, TEAEs resulting in study treatment discontinuation, TESAEs, and drug-related TESAEs will be tabulated by SOC, PT, and severity.
• Vital signs (blood pressure) [ Time Frame: From screening up to follow-up (Week 28) ]
  Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
• Vital signs (pulse rate) [ Time Frame: From screening up to follow-up (Week 28) ]
  Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
• Vital signs (temperature) [ Time Frame: From screening up to follow-up (Week 28) ]
  Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.
• Vital signs (respiratory rate) [ Time Frame: From screening up to follow-up (Week 28) ]
  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) [ Time Frame: From screening up to follow-up (Week 28) ]
  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 [ Time Frame: From screening up to follow-up (Week 28) ]
  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) [ Time Frame: From screening up to follow-up (Week 28) ]
  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) [ Time Frame: From screening up to follow-up (Week 28) ]
  Responses to the suicidality assessment scale (C-SSRS) will be listed.

Current Secondary Outcome Measures (submitted: November 15, 2023)

• Plasma concentration of ONO-2808 [ Time Frame: 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.
• ONO-2808 concentration in cerebrospinal fluid (CSF) [ Time Frame: Week 24 ]
  Descriptive summary statistics will be calculated for ONO-2808 CSF concentrations, by dose level and time point.

Original Secondary Outcome Measures (submitted: June 20, 2023)

• Plasma concentration of ONO-2808 [ Time Frame: 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.
• ONO-2808 concentration in CSF [ Time Frame: Week 24 ]
  Descriptive summary statistics will be calculated for ONO-2808 CSF concentrations, by dose level and time point.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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 to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Potential Efficacy of Multiple Doses of ONO-2808 in Patients With Multiple System Atrophy (MSA)
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Multiple System Atrophy (MSA)

Intervention

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

Study Arms

• Experimental: ONO-2808 Arm
  Intervention: Drug: ONO-2808
• Placebo Comparator: Placebo Arm
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 20, 2023): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2025
• Estimated Primary Completion Date: August 31, 2025 (Final data collection date for primary outcome measure)

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Ono Pharma USA, Inc.; clinical_trial@ono-pharma.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05923866
• Other Study ID Numbers: ONO-2808-03
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Ono Pharmaceutical Co. Ltd
• Original Responsible Party: Same as current
• Current Study Sponsor: Ono Pharmaceutical Co. Ltd
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Project Leader; Ono Pharma USA Inc

• PRS Account: Ono Pharmaceutical Co. Ltd
• Verification Date: May 2024