Expansion Study of ALT001 in Patients With Multiple System Atrophy

Expansion Study of ALT001 in Patients With Multiple System Atrophy

This is an open-label, single-center, prospective, single-arm clinical study. The primary objective of this study is to evaluate the safety, tolerability, and preliminary efficacy of ALT001 in the treatment of patients with multiple system atrophy (MSA) in a real-world setting.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by a blend of autonomic dysfunction, Parkinson's syndrome, and cerebellar syndrome. The incidence of MSA ranges from 1.9 to 4.9 per 100,000 individuals, with an average age of onset of 56.2 years. Among individuals aged 50 years and older, the prevalence stands at 3.0 per 100,000. The mean age of MSA onset is 56.2 years, and the median survival ranges from 6.2 to 7.5 years. MSA often presents with severe autonomic dysfunction early in its course, impacting patient survival. Furthermore, due to difficulties in early diagnosis, rapid progression, and poor prognosis, nearly 50% of patients require a walking aid or physical assistance for ambulation within three years of motor symptom onset. Within five years, 60% of patients become wheelchair-dependent, and after six to eight years, most are completely bedridden, severely compromising their quality of life. Current symptomatic and supportive therapies fall short of meeting the treatment requirements of MSA patients. Furthermore, potential adverse effects and disease progression factors restrict the use of certain drugs, highlighting the critical need for the development of disease-modifying or neuroprotective agents to decelerate disease advancement. "ALT001, a nerve repair protein created by Darwin Origin (Hubei) Biopharmaceutical Co.LTD, is derived from cellular exosomes, a set of specific microenvironmental protein polymers secreted by stem cells under emergency conditions. It boasts selective assembly, targeted delivery, highly efficient tissue repair, exceptional safety, chemical stability, and convenient storage. Previous basic research has indicated ALT001's potential for promoting endogenous neural tissue repair, exhibiting significant neuroprotective and neurorestorative effects in animal models. Therefore, building upon the previously initiated study of ALT001 in patients with the MSA-P subtype and the forthcoming study in patients with the MSA-C subtype, we are broadening the inclusion and exclusion criteria to evaluate the safety, tolerability, and efficacy of ALT001 in the treatment of MSA in a real-world setting. This study aims to recruit 60 MSA patients aged between 30 and 75 years. All participants will receive three cycles of ALT001 treatment, with each cycle lasting 30 days. ALT001 will be administered via intravenous infusion (130 μg) during the first 14 days of each cycle. Assessments including vital signs, laboratory tests (e.g., routine blood tests, blood biochemical examinations, coagulation tests), and neurological evaluations (e.g., Unified Multiple System Atrophy Rating Scale [UMSARS] and Composite Autonomic Symptom Score [COMPASS]) will be conducted at each cycle and at 180 days post-treatment. Additionally, if patients experience new neurological symptoms or suspicious events, additional visits will be carried out, and researchers are required to submit and interpret relevant data within 72 hours of the event occurrence.The protocol of this study has been approved by the Ethics Committee of Beijing Tiantan Hospital. All participants will provide written informed consents before entering the study.

Inclusion Criteria:

• 1. Age between 30 and 75 years inclusive, either sex;
• 2. Clinically established or clinically probable MSA (including both MSA-C and MSA-P subtypes);
• 3. Ability to walk independently or with the aid of a walking device for at least 10 meters;
• 4. Provision of written informed consent.

Exclusion Criteria:

• 1. Evidence of other central nervous system pathologies on brain MRI at screening suggesting a diagnosis of neurodegenerative diseases other than MSA;
• 2. Other significant pathological findings on brain MRI at screening, including but not limited to: cerebral hemorrhage, acute cerebral infarction, aneurysm, vascular malformation, infectious lesions, brain tumors, or other space-occupying lesions (meningiomas or arachnoid cysts with a maximum diameter <1 cm do not require exclusion);
• 3. Presence of immune-mediated diseases that are inadequately controlled or require treatment with biologic agents;
• 4. Known history of allergies to biologic agents, such as proteins or cell-based products;
• 5. Receipt of any vaccination within the past 1 month;
• 6. Patients with a prior definitive diagnosis of malignancy or those currently receiving anti-tumor drug therapy;
• 7. Patients with a prior definitive diagnosis of epilepsy or those currently taking anti-epileptic drugs;
• 8. Concurrent severe hepatic insufficiency, renal insufficiency, or severe cardiac insufficiency (severe hepatic insufficiency defined as ALT ≥1.5 times the upper limit of normal or AST ≥1.5 times the upper limit of normal; severe renal insufficiency defined as serum creatinine [CRE] ≥1.5 times the upper limit of normal or estimated glomerular filtration rate [eGFR] <40 mL/min/1.73 m²; severe cardiac insufficiency defined as NYHA class 3-4), or any significant abnormalities on physical examination, vital signs, laboratory tests, or electrocardiogram that, in the investigator's opinion, require further examination or treatment, or may interfere with the study procedures or safety;
• 9. Patients with a history of alcohol or substance abuse, or alcohol or substance dependence within the past 2 years;
• 10. Patients diagnosed with psychiatric disorders according to DSM-V criteria, or those with obvious suicidal intent;
• 11. Patients who are pregnant, lactating, or have the potential to become pregnant, or those planning a pregnancy;
• 12. Inability to comply with follow-up assessments due to other reasons;
• 13. Patients deemed by the investigator to be unsuitable for participation in this study.