Expansion Study of ALT001 in Patients With Multiple System Atrophy (ALT001 in MSA)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple System Atrophy
• Intervention / Treatment: Drug: ALT001

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Weiqi Chen; Phone Number: 8615652813380; Email: weiqichen@aliyun.com
• Study Contact Backup: Name: Yahui Zhu; Phone Number: 8613439182912; Email: zhuyahuidr@sina.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100070
      • Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intervention group; Intravenous administration of ALT001 was given to each MSA patient in the intervention group, with intravenous administration on days 1 to 14, 31 to 44±3 and 61 to 74±5, and treatment was given once a day. Intravenous administration: ALT001 (130 μg/branch) was dissolved in 100 ml sodium chloride injection, which was completed in about 30-40 minutes.

Drug: ALT001; "ALT001" is a nerve repair protein developed by Darwin Start (Hubei) Biopharmaceutical Co., Ltd. It is a group of specific microenvironmental protein polymers secreted under the emergency conditions of stem cells. It has the advantages of selective assembly, targeted delivery, efficient repair of damaged tissues, high safety, chemical stability, easy storage, etc., and has a powerful neural repair function. According to the groups, patients would be treated with ALT001 via intrathecal injection or intravenous injection. Intravenous administration of ALT001 was given to each MSA patient in the intervention group, with intravenous administration on days 1 to 14, 31 to 44±3 and 61 to 74±5, and treatment was given once a day. Intravenous administration: ALT001 (130 μg/branch) was dissolved in 100 ml sodium chloride injection, which was completed in about 30-40 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of adverse events (AEs) and serious adverse events (SAEs)	Incidence of adverse events (AEs) and serious adverse events (SAEs) within 180±7 days after treatment.	Day 180±7 after treatment
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) is composed of four subscales: UMSARS-I (12 items) rates patient-reported functional disability, UMSARS-II (14 items) assesses motor impairment based on a clinical examination, UMSARS-III records blood pressure and heart rate in the supine and standing positions, and UMSARS-IV (1 item) rates chore-based disability. Higher scores on the UMSARS indicate greater disability.	Day 15, 45±3, 75±5, and 180±14 after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 15, 45±3, 75±5, and 180±14 after treatment
Changes in the incidence of orthostatic hypotension	Changes in the incidence of orthostatic hypotension in patients on days 15, 45±3, 75±5, and 180±14 after treatment as measured by recumbent-upright blood pressure monitoring/24-hour ambulatory blood pressure monitoring/head-upright tilt test.	Day 15, 45±3, 75±5, and 180±14 after treatment
Variation of three-dimensional gait analysis parameters under multitasking	Changes in three-dimensional gait analysis parameters under multitasking in patients on day 180±14 after treatment.	Day 180±14 after treatment
Changes in the EQ-5D scores	The EuroQol Five-Dimensional Questionnaire (EQ-5D) is a standardized, generic instrument for measuring health-related quality of life. It comprises a descriptive system and the EuroQol Visual Analogue Scale (EQ VAS). The descriptive system encompasses five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has three (EQ-5D-3L) or five (EQ-5D-5L) levels of severity, generating a five-digit code that describes the respondent's health state. The primary function of the EQ-5D is to assess an individual's current overall health status, and it enables the calculation of a health utility index through value sets. It is widely used in clinical outcome assessment, population health surveys, and health economic evaluations.	Day 180±14 after treatment
Changes in plasma biomarkers (NFL, α-syn, GFAP)	Changes in NFL, α-syn, GFAP in plasma on days 15, 45±3, 74±5, 180±14 after treatment.	Day 15, 45±3, 75±5, and 180±14 after treatment

Collaborators and Investigators

• Sponsor: yilong Wang
• Investigators: Principal Investigator: Yilong Wang, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Principal Investigator: Tao Feng, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

Study record dates

Study Major Dates

• Study Start (Estimated): May 6, 2026
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Multiple system atrophy
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Basal Ganglia Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Multiple System Atrophy
• Other Study ID Numbers: KY2026-048-01; HX-A-2025122 (Other Identifier: National Medical Center for Neurological Diseases Office)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No