The Study of Safety and Preliminary Efficacy of ALT001 in Patients With MultIple System Atrophy-Cerebellar Type

The incidence of investigator-reported adverse events (AEs) and serious adverse events (SAEs)

The incidence of investigator-reported adverse events (AEs) and serious adverse events (SAEs)

The incidence of changes in clinical laboratory test parameters, changes in vital signs, neurological examination abnormalities and ECG abnormalities

Laboratory tests include: routine blood test, coagulation test, blood biochemical examination, urinalysis (note that abnormal changes in laboratory test results may need to be reviewed to further determine and assess their relevance to the study). Vital signs include: abnormal body temperature (≥38℃ or ≤35℃), blood pressure (systolic blood pressure ≥180mmHg or \<90mmHg), respiration (\>24 beats/min and other rhythm abnormalities), and heart rate (\>100 beats/min or \<60 beats/min).

Changes in the unified multiple system atrophy rating scale (UMSARS) part scores, sum of part 1 and 2 scores

The Unified Multiple System Atrophy Rating Scale (UMSARS) comprises four sections. Part I is the "Historical Review," consisting of 12 items that evaluate impairment in activities of daily living as reported by the patient. Each item is scored from a minimum of 0 points (normal) to a maximum of 4 points (severe disability), resulting in a total score range for this section of 0 to 48. Part II is the "Motor Examination," which assesses motor impairment based on clinical examination. It contains 14 items, each also scored from a minimum of 0 (normal) to a maximum of 4 (severe disability), yielding a total score range of 0 to 56. Part III is the "Autonomic Examination." Part IV is the "Global Disability Scale," a single-item scale used to assess the patient's overall level of disability, with scores ranging from a minimum of 1 (completely independent) to a maximum of 5 (totally bedridden).

Changes in the scale for the assessment and rating of ataxia (SARA)

The Scale for the Assessment and Rating of Ataxia (SARA) is a semi-quantitative clinical instrument designed to quantify the severity of cerebellar ataxia, with total scores ranging from 0 (no ataxia) to 40 (most severe ataxia). The scale comprises eight items that reflect progressively increasing functional impairment, assessing gait (0-8 points), stance (0-6 points), sitting (0-4 points), speech disturbance (0-6 points), finger chase (0-4 points), nose-finger test (0-4 points), fast alternating hand movements (0-4 points), and heel-knee-shin slide (0-4 points). For the upper and lower limb items, both sides are assessed separately, and the mean score is calculated for inclusion in the total score. SARA demonstrates good reliability and validity and is commonly used in clinical practice to evaluate the severity of ataxia and monitor disease progression.

Changes in the composite autonomic symptom score (COMPASS) scores

The Composite Autonomic Symptom Score (COMPASS) is a revised version of the 169-item Autonomic Symptom Profile assessing 11 domains of autonomic function, to the 31-item COMPASS, now assessing six domains: orthostatic hypotension (maximum score 10), vasomotor (maximum score 6), secretomotor (maximum score 7), gastrointestinal (maximum score 28), bladder (maximum score 9), and pupillomotor functions (maximum score 15). Scores from each component are recorded and a weighted total score is calculated. Higher scores on this scale indicate more severe clinical symptoms related to autonomic dysfunction. It is a validated, easy-to-use self-assessment instrument designed for clinical autonomic research and practice.

Changes in the incidence of orthostatic hypotension

Changes in the incidence of orthostatic hypotension in patients on days 15, 45±3, 75±5, 90±7, 180±14, and 360±14 after randomization as measured by recumbent-upright blood pressure monitoring/24-hour ambulatory blood pressure monitoring/head-upright tilt test.

Changes in postvoid residual urine volume (bladder ultrasound)

Changes in postvoid residual urine volume (ml) (bladder ultrasound) in patients on day 90±7, 180±14, and 360±14 after randomization

Changes in plasma biomarkers (NFL, α-syn, GFAP)

Changes in NFL (pg/ml), α-syn (pg/ml), GFAP (pg/ml) in plasma on days 15, 30±3, 60±5, 90±7, 180±14, and 360±14 after randomization. NFL (Neurofilament Light Chain) is a marker of axonal injury, reflecting the degree of neurodegeneration. α-syn (α-Synuclein) is a pathological hallmark protein in synucleinopathies like Parkinson's disease. GFAP (Glial Fibrillary Acidic Protein) indicates astroglial activation, suggesting CNS damage or inflammation.

Changes in cerebrospinal fluid biomarkers (α-Syn SAA, NFL, α-syn, GFAP)

Changes in α-Syn SAA, NFL (pg/ml), α-syn (pg/ml), GFAP (pg/ml) in cerebrospinal fluid on days 31±3 and 61±5 after randomization. α-Syn SAA enables ultrasensitive quantification of α-synuclein for early diagnosis of synucleinopathies. NFL is a marker of axonal injury, indicating neurodegeneration severity. α-syn is the pathological hallmark protein in synucleinopathies. GFAP indicates astroglial activation, reflecting CNS damage or inflammation.

Changes in 3T MRI imaging features

Longitudinal change rate of pontine volume (or AP diameter); longitudinal change rate of middle cerebellar peduncle (MCP) volume (or transverse diameter); longitudinal change rate of cerebellar white matter volume.