Clinical Trials

Inclusion Criteria

• Participant must be ≥ 30 and ≤ 80 years of age, at the time of signing the informed consent.
• 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)20, 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 UMSARS 1 total score (excluding item 1.11 sexual function) of ≤ 17.
• 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.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner, as recommended by local guidelines relating to contraception during clinical trials.
• Participants providing informed consent directly (or through their legal authorized representatives) after reading the information and consent form and after having the opportunity to discuss the study with the Investigator or designee.

Other Inclusion Criteria:

• Patients who agree to comply with the restrictions and requirements of the study.
• For menopausal women, Follicle-Stimulating Hormone (FSH) test confirmation is required.
• Patients vaccinated for SARS-CoV-2 (received primary series of COVID-19 vaccine) prior to Screening.
• Participants must be able to understand the nature of the study, the risks, discomforts, and inconveniences involved in the study, to communicate satisfactorily with the Investigator, and to participate and comply with the requirements of the entire study.

Exclusion Criteria:

• 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.
• For patients receiving treatment (including chronic medications and supplements) for symptoms associated with MSA, the dosage must have been stable for at least 30 days prior to randomization, based on the judgment of the Investigator; any medication is expected to remain stable during the study period.
• History of electroconvulsive therapy and/or history of deep brain stimulation therapy.
• Patients taking drugs prohibited by the study protocol, as outlined in the Prohibited Medication section.
• Regular use of neuroleptics within 6 months prior to the initial evaluation. Occasional use of a neuroleptic as an anti-emetic in the past is allowed, providing not more than 3 doses were taken within the previous 12 months.
• Patients who have taken any investigational products within 14 days or five half-lives (whichever is longer) of first dosing and throughout the study.
• Patients presenting with a cognitive problem that could impair their comprehension of study procedures and participation in the study, as assessed by a MoCA score < 20.
• Clinically-significant ECG abnormality as judged by the Investigator.
• Confirmed absolute QTc > 450 msec for males and > 470 msec for females and/or an increase of > 60 msec on repeated ECGs performed at least 2 minutes apart.
• Patients with a contraindication for MRI scanning, including those with an MRIincompatible pacemaker.
• Women of childbearing potential (WOCBP) who do not practice an acceptable method of birth control, as recommended by local guidelines [acceptable methods of birth control in this study are: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy, a double-protection method (condom or diaphragm with spermicide)].
• Patients consuming more than moderate levels of alcohol, defined as more than 1 standard drink per day for women and more than 2 standard drinks per day for men.
• For those undertaking CSF sampling, contraindications to undergoing a LP include:
  • Anticoagulant treatments;
  • Abnormal coagulopathy panel;
  • History of back pain or surgery;
  • Significant kyphosis and/or scoliosis or other spinal column deformities;
  • History or evidence of fundoscopy suggestive of raised intracranial pressure;
  • Inability to tolerate an appropriately-flexed position for the time necessary to perform an LP;
  • Infection at the desired LP site;
  • Taking antiplatelet/anticoagulant medications that cannot be discontinued for a short period of time prior to performing the LP;
  • Degenerative arthritis of the lumbar spine;
  • Suspected non-communicating hydrocephalus or intracranial mass;
  • Prior history of spinal mass or trauma;
  • Allergy or contraindication to the local anesthetic required for patients undergoing the LP.
• **Other clinically-significant or unstable medical or surgical conditions may include:
  • Severe uncontrolled congestive heart failure;
  • Recent (< 6 months) myocardial infarct;
  • Severe uncontrolled cardiopulmonary disease;
  • Severe, uncontrolled hypertension (sustained systolic blood pressure above 200 mmHg in any position);
  • Thrombocytopenia (< 50 × 10^9 /L);
  • Severe anemia (< 8 g/dL);
  • Immunocompromised state;
  • Liver (ALT, AST > ULN; TB > ULN) or kidney disease (creatinine > 1.5 mg/dL, creatinine clearance [using Cockcroft-Gault equation] < 60 mL/min, or proteinuria > 20 mg/dL)  Uncontrolled diabetes mellitus (HbA1c >10%);
  • Alcoholism;
  • Amyloidosis;
  • Uncontrolled hypothyroidism;
  • Sympathectomy;
  • Unstable peripheral neuropathies;
  • Concurrent infections;
  • Severe orthopedic problems that compromise mobility and activity of daily living;
  • Recent (< 6 months) cerebrovascular accidents;
  • Neurotoxin or neuroactive drug exposure.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 5/3/23. Questions regarding updates should be directed to the study team contact.