The Study of Safety and Preliminary Efficacy of Aleeto in Patients With MultIple System Atrophy

NCT06765733 | Recruiting Early Phase 1 DMC

• 1 other identifier: KY2024-314-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-center, prospective, randomized, open-label, blinded outcome assessment (PROBE) study. At the end of the PROBE study, patients who have completed the study may opt to enter the open-label extension (OLE) study. The objective of the study is to evaluate the safety, tolerability and potential preliminary efficacy of Aleeto in the treatment of patients with multiple system atrophy (MSA).

Conditions

Multiple System Atrophy - Parkinsonian Subtype (MSA-P); Multiple System Atrophy, MSA

Keywords

Multiple System Atrophy; Treatment; Exosomes; Neurorepair

Outcome Measures

Primary Outcomes (2)

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

  Incidence of investigator-reported adverse events (AEs) and serious adverse events (SAEs) within 90±7 days after randomization;

  Day 90±7 after randomization

• 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), heart rate (\>100%), and blood pressure (\<10%).

  Day 90±7 after randomization

Secondary Outcomes (10)

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

  Day 15, 45±3, 75±5 and 90±7 after randomization

• Changes in the composite autonomic symptom score (COMPASS) scores

  Day 15, 45±3, 75±5 and 90±7 after randomization

• Changes in the incidence of orthostatic hypotension

  Day 15, 45±3, 75±5 and 90±7 after randomization

• Variation of three-dimensional gait analysis parameters under multitasking

  Day 90±7 after randomization

• EuroQol Five Dimensions Questionnaire (EQ-5D)

  Day 90±7 after randomization

Other Outcomes (5)

• Changes in postvoid residual urine volume (bladder ultrasound) in patients;

  Day 90±7 after randomization

• Changes in plasma biomarkers (NFL, α-syn, Tau protein, Aβ40/42/43, YKL-40, CoQ10, UA, Hcy, and other biomarkers) associated with neural repair, vascular endothelial injury, inflammatory factors and histology

  Day 15, 30±3, 60±5, 90±7, 180±14, and 360±14 after randomization

• Changes in plasma biomarkers (NFL, α-syn, Tau protein, Aβ40/42/43, YKL-40, CoQ10, UA, Hcy, and other biomarkers) associated with neural repair, vascular endothelial injury, inflammatory factors and histology

  Day 31±3 and 61±5 after randomization

Study Arms (2)

Intervention group

EXPERIMENTAL

Intrathecal administration combined with intravenous administration of Aleeto of Aleeto was given to each MSA patient in the intervention group, with intrathecal administration on days 1, 31 and 61 and intravenous administration on days 2 to 14, 32 to 44±3 and 62 to 74±5, and treatment was given once a day. intrathecal administration: 8 mL sodium chloride injection + Aleeto (130 μg/branch) for intrathecal administration, which was completed in about 5 minutes; intravenous administration: Aleeto (130 μg/branch) was dissolved in 100 ml sodium chloride injection, which was completed in about 30-40 minutes. After completion of the above treatments and 90±7 days of follow-up, all subjects entered the OLE study phase. During this period, all participants were given the option of continuing to receive 3 phases (on Days 91 to 104±7, Days 121 to 134±7, and Days 151 to 164±7) of intravenous Aleeto administration (14 consecutive days of Aleeto 130 μg qd i.v. in each phase).

Drug: Aleeto

Control group

NO INTERVENTION

Each MSA patient in the blank control group received only basic treatment with no trial-related treatment. After completion of the above treatments and 90±7 days of follow-up, all subjects entered the OLE study phase. During this period, all participants were given the option of continuing to receive 3 phases (on Days 91 to 104±7, Days 121 to 134±7, and Days 151 to 164±7) of intravenous Aleeto administration (14 consecutive days of Aleeto 130 μg qd i.v. in each phase).

Interventions

Aleeto DRUG

"Aleeto" is a nerve repair protein developed by Darwin Start (Beijing) 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 Aleeto via intrathecal injection or intravenous injection.

Intervention group

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years ≤ 75 years of age, regardless of sex; 2.Clinically confirmed or clinically probable MSA-P; 3.Poor response to levodopa; 4.MSA-related motor symptom onset ≤5 years at first visit; 5.Walking ≥10 meters independently or with a walking aid; 6.Expected survival of ≥1 year, as determined by the investigator; 7.Signed informed consent.

You may not qualify if:

• Head MRI at screening showing evidence of other CNS lesions consistent with a diagnosis of neurodegenerative disease other than MSA;
• Patients with MMSE scores indicative of dementia prior to enrolment (≤17 points for illiterate individuals, ≤20 points for individuals with elementary school education, ≤24 points for individuals with junior high school education or higher) or those with a prior confirmed diagnosis of dementia;
• Head MRI at screening showing other significant pathological findings including but not limited to: cerebral hemorrhage, acute phase of cerebral infarction, aneurysm, vascular malformation, infectious lesion, brain tumor or other space-occupying lesion (meningiomas or arachnoid cysts with a maximum diameter of \<1 cm need not be excluded);
• Presence of immune disorders that are inadequately controlled or require treatment with biological agents;
• Known history of allergy to biological agents such as proteins and cell products;
• Patients who have received any vaccination within 1 month;
• Patients with pre-existing, clearly diagnosed malignant tumor or being treated with anti-tumor drugs;
• Patients with a history of clearly diagnosed epilepsy or taking antiepileptic drugs;
• Presence of lumbar spine disease and deformity or other contraindications to lumbar puncture;
• Patients with abnormal coagulation function prior to enrolment (e.g., platelet count \<100 × 10E9/L; prothrombin time \[PT\] \>3 s), previous diagnosis of coagulation disorders such as hemophilia, and patients currently receiving more than two types of antiplatelet medication;
• Contraindications to MRI (e.g. claustrophobia, internal placement of pacemakers or paramagnetic metals, etc.);
• With severe hepatic insufficiency, renal insufficiency or severe cardiac insufficiency (severe hepatic insufficiency refers to ALT value≥2.0 times the upper limit of normal value or AST value≥2.0 times the upper limit of normal value; severe renal insufficiency refers to CRE≥1.5 times the upper limit of normal value or eGFR\<40mL/min/1.73m2; severe cardiac insufficiency refers to NYHA class 3-4);
• Hepatitis B active infection (hepatitis B surface antigen positive and/or serum HBV DNA positive or serum HBV DNA \> 2 × 10E8 IU/ml;
• Hepatitis C virus antibody positive or history of positive test;
• Positive HIV test or history of positive test;

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100070, China

RECRUITING

MeSH Terms

Conditions

Multiple System Atrophy; Thyroid Dyshormonogenesis 2A

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Officials

• Yilong Wang, M.D.

  Beijing Tiantan Hospital, Capital Medical University, Beijing, China

  PRINCIPAL INVESTIGATOR

• Tao Feng, M.D.

  Beijing Tiantan Hospital, Capital Medical University, Beijing, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weiqi Chen, M.D.

CONTACT

8615652813380; weiqichen@aliyun.com

Lei Guo

CONTACT

8619801237597; guolei53@aliyun.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President of Beijing Tiantan Hospital

Study Record Dates

• First Submitted: November 26, 2024
• First Posted: January 9, 2025
• Study Start: May 31, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)