A Prospective Exploratory Study of the Safety and Preliminary Efficacy of the α-Syn H21 Monoclonal Antibody in Patients With Multiple System Atrophy

Incidence, severity, and relationship of adverse events (AEs) and serious adverse events (SAEs) to study treatment.

Change from baseline in the total score and subscale scores of the Unified Multiple System Atrophy Rating Scale (UMSARS Parts I-IV). The UMSARS is a clinician-administered scale used to assess disease severity in patients with multiple system atrophy. Total scores are derived from Parts I-IV, with higher scores indicating greater disease severity and worse clinical status. The total score ranges from 0 to 249, with higher scores indicating more severe impairment.

Change from baseline in DAT-PET/MRI imaging parameters, including brain metabolic and structural changes.

Change from baseline in the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS Parts I-IV) total and subscale scores. The MDS-UPDRS is a clinician-administered scale used to assess the severity and progression of Parkinsonian symptoms. The total score ranges from 0 to 260, with higher scores indicating greater disease severity and worse motor and non-motor impairment.

The Patient Global Impression of Improvement (PGI-I) is a patient-reported measure assessing overall perceived improvement following treatment. Scores range from 1 (very much improved) to 7 (very much worse), with lower scores indicating better perceived improvement.

Change from baseline in the Mini-Mental State Examination (MMSE) score. The MMSE is a widely used clinician-administered screening tool for global cognitive function, assessing domains including orientation, attention, memory, language, and visuospatial abilities. Scores range from 0 to 30, with higher scores indicating better cognitive function and lower scores indicating greater cognitive impairment.

Change from baseline in the Hamilton Depression Rating Scale (HAMD) score. The HAMD is a clinician-administered scale used to assess the severity of depressive symptoms. Scores range from 0 to 52 (17-item version), with higher scores indicating more severe depressive symptoms and lower scores indicating less severe depression.

Change from baseline in the Hamilton Anxiety Rating Scale (HAMA) score. The HAMA is a clinician-administered scale used to assess the severity of anxiety symptoms. Scores range from 0 to 56, with higher scores indicating more severe anxiety symptoms and lower scores indicating less severe anxiety.

Change from baseline in the Parkinson's Disease Sleep Scale-2 (PDSS-2) score. The PDSS-2 is a patient-reported scale used to assess the severity of nocturnal disturbances and sleep-related symptoms in patients with Parkinson's disease. Scores range from 0 to 60, with higher scores indicating more severe sleep disturbances and poorer sleep quality.

Change from baseline in the Parkinson's Disease Questionnaire-39 (PDQ-39) score. The PDQ-39 is a patient-reported questionnaire used to assess health-related quality of life in patients with Parkinson's disease across eight domains, including mobility, activities of daily living, emotional well-being, and social support. Scores range from 0 to 156, with higher scores indicating poorer health-related quality of life and greater disease impact.

The number of participants with clinically significant abnormal laboratory values following H21 administration, including abnormalities in hematology, urinalysis, liver function, and renal function tests, as assessed by the investigator.

Standard 12-lead electrocardiograms will be performed at scheduled visits to assess changes from baseline in cardiac conduction and rhythm parameters, including heart rhythm, PR interval, QRS duration, and corrected QT (QTc) interval, following H21 administration.

Change in blood pressure measured before each H21 infusion and at 10 minutes and 30 minutes after infusion to evaluate short-term hemodynamic changes associated with study drug administration.

Change in heart rate measured before each H21 infusion and at 10 minutes and 30 minutes after infusion to evaluate short-term cardiac responses associated with study drug administration.

Change in respiratory rate measured before each H21 infusion and at 10 minutes and 30 minutes after infusion to evaluate short-term respiratory changes associated with study drug administration.

Serum concentrations of H21 will be measured at prespecified time points following administration to characterize the concentration-time profile of H21.

The maximum observed serum concentration (Cmax) of H21 following administration.

The time to reach the maximum observed serum concentration (Tmax) of H21 following administration.

The area under the serum concentration-time curve (AUC) of H21 following administration.

The terminal elimination half-life (t1/2) of H21 following administration.