RecruitingPhase 1Phase 2NCT06598202

Exploring Nasal Drop Therapy With Small Extracellular Vesicles for ALS

An Exploratory Study on the Use of Intranasal Administration of Small Extracellular Vesicles for the Treatment of Amyotrophic Lateral Sclerosis

Sponsor

Xuanwu Hospital, Beijing

Enrollment

38 participants

Start Date

Dec 1, 2024

Study Type

INTERVENTIONAL

Conditions

Amyotrophic Lateral Sclerosis

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.

Eligibility

Min Age: 18 YearsMax Age: 80 Years

Inclusion Criteria9

Age: 18-80 years, inclusion of both genders;
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.

Exclusion Criteria16

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;
Any other conditions deemed unsuitable for inclusion by the investigators.

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Interventions

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

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).

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

Exosomes placebo