Multiple System Atrophy
Conditions
Brief summary
Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic dysfunction, parkinsonism, and cerebellar ataxia. Abnormal aggregation of alpha-synuclein is believed to play an important role in disease progression. The α-Syn H21 monoclonal antibody is designed to selectively bind pathological alpha-synuclein aggregates and may reduce their spread and related neuroinflammation. This single-center, prospective, exploratory study will evaluate the safety, tolerability, and preliminary efficacy of the α-Syn H21 monoclonal antibody in patients with MSA. Participants will receive intravenous infusions of H21 every 4 weeks for 3 doses and will be followed for 12 weeks. Clinical symptoms, laboratory tests, imaging findings, and adverse events will be assessed to determine whether H21 may provide clinical benefit and support future larger studies.
Interventions
BIOLOGICALα-Syn H21 Monoclonal Antibody
The α-Syn H21 monoclonal antibody is a humanized monoclonal antibody designed to selectively bind pathological alpha-synuclein aggregates. Participants will receive the study drug by intravenous infusion once every 4 weeks for a total of 3 doses during the 12-week study period.
Sponsors
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 45 to 75 years, male or female * Diagnosis of Multiple System Atrophy meeting current clinical diagnostic criteria for probable or possible MSA * Disease duration of 2 years or less from onset of motor or autonomic symptoms * Clinically stable disease without significant fluctuation or acute worsening within 4 weeks before enrollment * Able to comply with study procedures and follow-up assessments * Mini-Mental State Examination (MMSE) score not consistent with significant dementia * Willing and able to provide written informed consent
Exclusion criteria
* History or presence of other neurological disorders that may interfere with study assessments, including Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration, or stroke * Severe cognitive impairment or psychiatric disorder, including clinically significant depression or anxiety * Severe cardiac, hepatic, renal, or other major systemic disease * History of severe hypersensitivity to monoclonal antibody therapies Pregnant or breastfeeding women * Women or men unwilling to use effective contraception during the study * Participation in another clinical trial or receipt of investigational treatment within 3 months before enrollment * Any other condition that, in the investigator's judgment, would make participation inappropriate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events | From first dose through Week 12 | Incidence, severity, and relationship of adverse events (AEs) and serious adverse events (SAEs) to study treatment. |
| Change from Baseline in Unified Multiple System Atrophy Rating Scale (UMSARS) Total Score (Parts I-IV) | Baseline, Week 4, Week 8, and Week 12 | 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 measures of striatal dopamine transporter uptake and brain structural changes | Baseline and Week 12 | Change from baseline in DAT-PET/MRI imaging parameters, including brain metabolic and structural changes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score | Baseline, Week 4, Week 8, and Week 12 | 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. |
| Change in Patient Global Impression of Improvement (PGI-I) Score | Baseline, Week 4, Week 8, and Week 12 | 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 Mini-Mental State Examination (MMSE) Score | Baseline, Week 4, Week 8, and Week 12 | 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 Hamilton Depression Rating Scale (HAMD) Score | Baseline, Week 4, Week 8, and Week 12 | 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 Hamilton Anxiety Rating Scale (HAMA) Score | Baseline, Week 4, Week 8, and Week 12 | 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 Parkinson's Disease Sleep Scale-2 (PDSS-2) Score | Baseline, Week 4, Week 8, and Week 12 | 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 Parkinson's Disease Questionnaire-39 (PDQ-39) Score | Baseline, Week 4, Week 8, and Week 12 | 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. |
| Number of Participants With Clinically Significant Abnormal Laboratory Values | Baseline, Week 4, Week 8, and Week 12 | 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. |
| Change from baseline in electrocardiogram parameters including heart rhythm, PR interval, QRS duration, and QTc interval | Baseline, Week 4, Week 8, and Week 12 | 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 After Infusion | Pre-dose and 10 minutes and 30 minutes after each infusion through Week 12 | 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 After Infusion | Pre-dose and 10 minutes and 30 minutes after each infusion through Week 12 | 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 After Infusion | Pre-dose and 10 minutes and 30 minutes after each infusion through Week 12 | 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 Concentration of H21 | During treatment through Week 12 | Serum concentrations of H21 will be measured at prespecified time points following administration to characterize the concentration-time profile of H21. |
| Maximum Observed Serum Concentration (Cmax) of H21 | During treatment through Week 12 | The maximum observed serum concentration (Cmax) of H21 following administration. |
| Time to Maximum Observed Serum Concentration (Tmax) of H21 | During treatment through Week 12 | The time to reach the maximum observed serum concentration (Tmax) of H21 following administration. |
| Area Under the Serum Concentration-Time Curve (AUC) of H21 | During treatment through Week 12 | The area under the serum concentration-time curve (AUC) of H21 following administration. |
| Terminal Elimination Half-life (t1/2) of H21 | During treatment through Week 12 | The terminal elimination half-life (t1/2) of H21 following administration. |
Countries
China
Contacts
CONTACTJun Liu, MD, PhD
CONTACTYan SHEN, MD, PhD
Outcome results
None listed