Exploring Nasal Drop Therapy With Small Extracellular Vesicles for ALS

NCT06598202 | Recruiting Phase 1 DMC

• 1 other identifier: XMEC-2024-267-002
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial. The goal of this clinical trial is to evaluate the safety and preliminary efficacy of nasal drop exosomes derived from human umbilical cord blood mesenchymal stem cells (hUC-MSC-sEV-001) in amyotrophic lateral sclerosis.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Neurodegenerative diseases; Inflammation; Motor neuron degeneration; Exosomes; Small extracellular vesicles

Outcome Measures

Primary Outcomes (1)

• Number of participants who experienced dose-limiting Toxicities (DLTs)

  DLTs related to hUC-MSC-sEV-001 include adverse events of grade 3 or higher (including significant clinical laboratory findings) that are possibly, likely, or definitely related to the study drug, accompanied by clinical symptoms and requiring medical treatment within 14 days of administration. Adverse events are graded according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0).

  24 hours, 4±1 Weeks

Secondary Outcomes (10)

• Incidence of severe adverse events

  4±1 Weeks

• Change from baseline in ALS functional rating scale - revised

  4±1 Weeks, 12±1 Weeks, 24±1 Weeks

• Change from baseline in forced vital capacity to predicted value ratio (FVC% pred)

  4±1 Weeks, 24±1 Weeks

• Time to event (death, tracheostomy, and permanent assisted mechanical ventilation)

  up to 24 Weeks

• Change from baseline in the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40).

  4±1 Weeks, 12±1 Weeks, 24±1 Weeks

Other Outcomes (2)

• Change from baseline in the neuroimaging indices.

  24±1 weeks

• Change from baseline in the blood markers.

  up to 24 weeks

Study Arms (2)

Exosomes group

EXPERIMENTAL

Patients in this arm will receive exosomes derived from human umbilical cord blood mesenchymal stem cells as a nasal drop, administered once daily, twice a week, for a total of two weeks.

Drug: exosomes derived from human umbilical cord blood mesenchymal stem cells for nasal drop

Exosomes placebo group

PLACEBO COMPARATOR

Patients in this arm will receive a placebo nasal drop mimicking exosomes derived from human umbilical cord blood mesenchymal stem cells, administered once daily, twice a week, for a total of two weeks.

Drug: a placebo of exosomes derived from human umbilical cord blood mesenchymal stem cells for nasal drop

Interventions

exosomes derived from human umbilical cord blood mesenchymal stem cells for nasal drop DRUG

Exosomes derived from human umbilical cord blood mesenchymal stem cells for nasal drop (administered once daily, twice a week, for a total of two weeks, based on the recommended dose during the dose-escalation phase).

Also known as: hUC-MSC-sEV-001

Exosomes group

a placebo of exosomes derived from human umbilical cord blood mesenchymal stem cells for nasal drop DRUG

Exosomes placebo

Also known as: hUC-MSC-sEV-001 placebo

Exosomes placebo group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Disease duration: ≥6 months and ≤2 years (counted from the onset of any ALS symptoms);
• Subjects must meet the El Escorial revised criteria (2000) for the diagnosis of ALS, with a diagnosis of Definite ALS, Probable ALS, Probable laboratory-supported ALS, or Possible ALS;
• A score of ≥2 on each item of the revised ALS Functional Rating Scale (ALSFRS-R), with a score of 4 for items related to dyspnea, orthopnea, and respiratory insufficiency;
• BMI: Between 18 and 30 kg/m²;
• Subjects must have a baseline forced vital capacity percentage (%FVC) ≥70%;
• Allowed concomitant treatments: Oral administration of riluzole/edaravone at standard doses for ≥30 days; regular intravenous edaravone with planned sequential oral treatment. During the trial and follow-up period, the dosage and type of concomitant medications must remain unchanged;
• Subjects of childbearing potential must use appropriate and effective contraception from 2 weeks prior to trial enrollment until the end of the follow-up period;
• The subject or legal representative must be able to sign an informed consent form and comply with the study requirements for medication administration and follow-up.

You may not qualify if:

• Diagnosed as non-ALS based on clinical presentation and available clinical examinations (e.g., neurophysiological tests, MRI, or other imaging, laboratory tests);
• Abnormal nasal anatomy, nasal cavity damage, severe rhinitis, or nasal disease affecting the administration of the study drug;
• Requires nasal insertion of a gastric tube;
• Peripheral venous hemoglobin (HGB) \< 100 g/L, absolute neutrophil count (NEUT) \< 1.5×10\^9/L, platelet count (PLT) \< 100×10\^9/L, white blood cell count (WBC) \< 4.0×10\^9/L or ≥ 12×10\^9/L, serum albumin \< 30 g/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3× the upper limit of normal (ULN);
• Severe renal insufficiency: Glomerular Filtration Rate (GFR) \< 30 mL/min (Cockcroft-Gault formula), or other known severe renal diseases;
• Positive for hepatitis B surface antigen, e antigen, e antibody, or core antibody combined with positive hepatitis B virus DNA; positive for hepatitis C virus antibody; positive syphilis serum antibody; or positive for HIV antibody;
• History of acute myocardial infarction or interventional treatment within the last 6 months, or heart failure (classified as NYHA III-IV);
• Presence of severe localized or systemic infection, immunodeficiency, or currently taking immunosuppressants;
• Concurrent severe systemic diseases such as immunodeficiency diseases, coagulation disorders, or malignancies;
• Vaccination within 1 month prior to the first administration or during the study until the end of follow-up;
• Known allergy to the drugs used in this study or similar drugs;
• Participation in another study and administration of an investigational product within the last 3 months;
• Contraindications to MRI (e.g., presence of metal implants) or inability to tolerate MRI (e.g., claustrophobia);
• Pregnant or breastfeeding women, or women of childbearing potential who cannot or are unwilling to use appropriate contraception;
• Unwillingness or inability to comply with the procedures required by the protocol;

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead
• Shengqi Medical Technology (Guangzhou) Co., Ltd.: collaborator
• Viyun (Xiamen) Biomedical Research Institute Co., Ltd.: collaborator

Study Sites (1)

Xuanwu Hospital ,Capital Medical University

Beijing, Beijing Municipality, 100053, China

RECRUITING

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Inflammation

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Junwei Hao, MD; PhD

  Xuanwu Hospital, Beijing

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Junwei Hao, MD; PhD

CONTACT

010 8319 8277; haojunwei@vip.163.com

Gaoting Ma, MD

CONTACT

010 8319 8082; demo_doctor@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Neurology Department

Study Record Dates

• First Submitted: September 10, 2024
• First Posted: September 19, 2024
• Study Start: December 1, 2024
• Primary Completion: May 30, 2026
• Study Completion: May 30, 2026
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)