Exploring Nasal Drop Therapy With Small Extracellular Vesicles for ALS

NCT ID: NCT06598202

Last Updated: 2024-10-31

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2026-05-30

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.

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial. The study will consist of two parts: Part 1 will be a dose-escalation study, and Part 2 will be an expanded safety study based on the findings from Part 1.

A traditional 3+3 dose-escalation design will be implemented in Part 1. Cohort 1 will receive low-dose; Cohort 2 will receive middle-dose; and Cohort 3 will receive high-dose. (Cohort 1 to Cohort 3 will receive a dose of 1 mL per nostril, administered once daily, twice a week, for a total of two weeks.) If no dose-limiting toxicities (DLTs) are observed for 2 weeks after the administration of the first nasal drop, a new cohort will be enrolled at the next planned dose level. If DLTs are observed in one participant in the cohort, an additional three participants will be treated at the same dose level. Dose escalation will be stopped if DLTs are observed in more than 33% of the participants.

In Part 2, 20 subjects will be randomized in a 1:1 ratio [exosome (n=10) or exosome placebo (n=10)]. The dose level will be determined by the primary researcher based on the findings from Part 1.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Exosomes group

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.

Group Type: EXPERIMENTAL

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

Intervention Type: 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).

Exosomes placebo group

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.

Group Type: PLACEBO_COMPARATOR

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

Intervention Type: DRUG

Exosomes placebo

Interventions

exosomes 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).

Intervention Type: DRUG

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

Exosomes placebo

Intervention Type: DRUG

Other Intervention Names

hUC-MSC-sEV-001; hUC-MSC-sEV-001 placebo

Eligibility Criteria

Inclusion Criteria

• 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 Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shengqi Medical Technology (Guangzhou) Co., Ltd.

UNKNOWN

Sponsor Role: collaborator

Viyun (Xiamen) Biomedical Research Institute Co., Ltd.

UNKNOWN

Sponsor Role: collaborator

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: lead

Responsible Party

Junwei Hao, MD

Director of Neurology Department

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Junwei Hao, MD; PhD

Role: PRINCIPAL_INVESTIGATOR

Xuanwu Hospital, Beijing

Locations

Xuanwu Hospital ,Capital Medical University

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Junwei Hao, MD; PhD

Role: CONTACT

haojunwei@vip.163.com

010 8319 8277

Gaoting Ma, MD

Role: CONTACT

demo_doctor@163.com

010 8319 8082

Facility Contacts

Gaoting Ma, MD

Role: primary

demo_doctor@163.com

01083198082

Other Identifiers

XMEC-2024-267-002

Identifier Type: -

Identifier Source: org_study_id