Back to resultsInduced Pluripotent Stem Cell Derived Exosomes Nasal Drops for the Treatment of Refractory Focal Epilepsy
Primary Purpose
Refractory Focal Epilepsy
Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
iPSC-Exos
Sponsored by
About this trial
This is an interventional treatment trial for Refractory Focal Epilepsy
Eligibility Criteria
Inclusion Criteria: Before conducting this study, understand and sign the informed consent form and comply with the requirements of this study; The subjects are patients with focal epilepsy aged 18 to 70 years (inclusive), regardless of gender; The subjects must comply with the definition of drug resistant epilepsy (ILAE); Subjects must take 1-6 types of anti-epileptic drugs (AEDs), and before entering the screening period, they must take unadjusted types and stable doses of AEDs for at least 4 weeks; Throughout the entire research process, the subject/legal guardian must be able to accurately record the log of epileptic seizures; Subjects must experience at least 4 countable seizures within 28 days prior to the screening period; The subjects are willing and able to comply with the research requirements. Exclusion Criteria: Unwilling or unable to follow the procedures stipulated in the agreement; Pregnant or lactating women, or women with reproductive potential who are unable or unwilling to take appropriate contraceptive measures; Other uncontrollable diseases that may interfere with the research results, including but not limited to infection, hypertension, diabetes, cardiovascular and cerebrovascular diseases, etc; There are situations that may increase the risk of participating in experiments or research product use, such as liver enzyme elevation exceeding twice the normal upper limit and/or GFR<60 mL/min/1.73 m2; Have a history of drug abuse, alcohol dependence, or smoking within one month; Patients with status epilepticus within one month; Have potential progressive nervous system disease, such as encephalitis, brain tumor, multiple sclerosis or dementia; Patients who plan to undergo epilepsy surgery within six months; Patients with abnormal or diseased nasal structures; Patients with cerebrospinal fluid rhinorrhea; Patients whose family members have not been able to proficiently and correctly master the nasal drip method through standardized training
Sites / Locations
- Peking Union Medical College HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
iPSC-exosome treatment
Arm Description
group1-low-dose group, 8 papatients are treated with 2 μg iPSC-Exos in 200 μL. group2-mid-dose group, 8 papatients are treated with 6 μg iPSC-Exos in 200 μL. group3-mid-dose group, 8 papatients are treated with 18 μg iPSC-Exos in 200 μL. group4-Dose expansion, 10 papatients are treated with iPSC-Exos in 200 μL. iPSC-Exos were administrated for nasal drip, bid for 12 weeks.
Outcomes
Primary Outcome Measures
adverse events as assessed by CTCAE
all potentially treated subjects to assess the safety
Secondary Outcome Measures
Number of participants with abnormal vital signs and abnormal Physical examination findings
Number of participants with abnormal Neurological examination
Evaluate general neurological status, muscle strength and tension, sensory ataxia, and pathological signs
Number of participants with abnormal laboratory tests results
Blood routine test, blood biochemistry test ,and electrolytes test
Number of participants with abnormal Urine analysis
Urine routine examination
Seizures frequency
Seizure frequency:
i. no seizures: any type of seizure disappeared after 28 days of observation; ii. significantly effective: 75%-99% reduction in seizure frequency compared with baseline; iii. Effective: 50%-75% reduction in seizure frequency compared with baseline; iv. Improvement: 25%-50% reduction in the number of seizures compared with baseline, or prolongation, reduction in degree, and shortening of duration between episodes; v. Ineffectiveness and exacerbation: Ineffectiveness refers to a decrease or increase of <25% in the number of seizures compared with baseline, and exacerbation refers to an increase in the frequency of seizures from baseline ≥25%.
Scalp electroencephalogram monitoring
Head magnetic resonance imaging (MRI) examination
Full Information
NCT ID
NCT05886205
First Posted
May 8, 2023
Last Updated
June 5, 2023
Sponsor
Peking Union Medical College Hospital
Collaborators
Guidon Pharmaceutics Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05886205
Brief Title
Induced Pluripotent Stem Cell Derived Exosomes Nasal Drops for the Treatment of Refractory Focal Epilepsy
Official Title
Exploratory Clinical Study on Induced Pluripotent Stem Cell Derived Exosomes (GD-iEXo-002) Nasal Drops for the Treatment of Refractory Focal Epilepsy
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 5, 2023 (Anticipated)
Primary Completion Date
June 13, 2025 (Anticipated)
Study Completion Date
November 13, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital
Collaborators
Guidon Pharmaceutics Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Evaluate the safety, tolerability, and preliminary efficacy of GD-iEXo-002 nasal drops in the treatment of focal refractory epilepsy
Detailed Description
Epilepsy patients can achieve good control after treatment, but still 30% of patients are medically refractory epilepsy, with the vast majority being focal epilepsy. Recurrent seizures seriously affect the normal development, learning, and life of patients. There is an urgent need for effective drugs to treat refractory focal epilepsy in clinical practice.
Exosomes are a kind of vesicle structures secreted by cells, with a diameter of 30-150 nm, carrying proteins, nucleic acids and other substances. Exosomes have many advantages. As naturally occurring nanoscale secretory membrane vesicles, they have extremely low immunogenicity and good safety, and can cross biological barriers such as the blood-brain barrier and the blood-tumor barrier. Exosomes have specific bioactive substances related to source cells, while stem cell exosomes contain TGF- β、 Functional factors such as BDNF can inhibit cell apoptosis, inhibit inflammatory response, promote angiogenesis, inhibit fibrosis, and enhance tissue repair potential, with a wide range of potential applications.
Induced pluripotent stem cell (iPSC) originates from single cell amplification, with infinite proliferation ability, good consistency and stability; MSCs exhibit significant heterogeneity.
The purpose of this single center, open label clinical trial is to evaluate the safety, tolerability, and preliminary efficacy of induced pluripotent stem cell derived exosomes (iPSC-Exos) nasal drops in the treatment of focal refractory epilepsy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Focal Epilepsy
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
iPSC-exosome treatment
Arm Type
Experimental
Arm Description
group1-low-dose group, 8 papatients are treated with 2 μg iPSC-Exos in 200 μL. group2-mid-dose group, 8 papatients are treated with 6 μg iPSC-Exos in 200 μL. group3-mid-dose group, 8 papatients are treated with 18 μg iPSC-Exos in 200 μL. group4-Dose expansion, 10 papatients are treated with iPSC-Exos in 200 μL. iPSC-Exos were administrated for nasal drip, bid for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
iPSC-Exos
Intervention Description
iPSC-Exos were administrated for nasal drip, bid for 12 weeks.
Primary Outcome Measure Information:
Title
adverse events as assessed by CTCAE
Description
all potentially treated subjects to assess the safety
Time Frame
24 weeks from post-administration
Secondary Outcome Measure Information:
Title
Number of participants with abnormal vital signs and abnormal Physical examination findings
Time Frame
Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
Title
Number of participants with abnormal Neurological examination
Description
Evaluate general neurological status, muscle strength and tension, sensory ataxia, and pathological signs
Time Frame
Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
Title
Number of participants with abnormal laboratory tests results
Description
Blood routine test, blood biochemistry test ,and electrolytes test
Time Frame
Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
Title
Number of participants with abnormal Urine analysis
Description
Urine routine examination
Time Frame
Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
Title
Seizures frequency
Description
Seizure frequency:
i. no seizures: any type of seizure disappeared after 28 days of observation; ii. significantly effective: 75%-99% reduction in seizure frequency compared with baseline; iii. Effective: 50%-75% reduction in seizure frequency compared with baseline; iv. Improvement: 25%-50% reduction in the number of seizures compared with baseline, or prolongation, reduction in degree, and shortening of duration between episodes; v. Ineffectiveness and exacerbation: Ineffectiveness refers to a decrease or increase of <25% in the number of seizures compared with baseline, and exacerbation refers to an increase in the frequency of seizures from baseline ≥25%.
Time Frame
before administration; administration; after the first administration 1 week,2 weeks,4 weeks,8 weeks,12 weeks,16 weeks,24 weeks
Title
Scalp electroencephalogram monitoring
Time Frame
Screening, after the first administration 12 weeks
Title
Head magnetic resonance imaging (MRI) examination
Time Frame
Screening, after the first administration 12 weeks
Other Pre-specified Outcome Measures:
Title
Exploratory research-1
Description
The protein concentration of GFAP, IL-1 β、 IL-6、IL-10、IL-17a、TGF- β、 MCP-1 and TNF- α in blood
Time Frame
Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
Title
Exploratory research-2
Description
T cell, B cell, NK cell subpopulation analysis
Time Frame
Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Before conducting this study, understand and sign the informed consent form and comply with the requirements of this study;
The subjects are patients with focal epilepsy aged 18 to 70 years (inclusive), regardless of gender;
The subjects must comply with the definition of drug resistant epilepsy (ILAE);
Subjects must take 1-6 types of anti-epileptic drugs (AEDs), and before entering the screening period, they must take unadjusted types and stable doses of AEDs for at least 4 weeks;
Throughout the entire research process, the subject/legal guardian must be able to accurately record the log of epileptic seizures;
Subjects must experience at least 4 countable seizures within 28 days prior to the screening period;
The subjects are willing and able to comply with the research requirements.
Exclusion Criteria:
Unwilling or unable to follow the procedures stipulated in the agreement;
Pregnant or lactating women, or women with reproductive potential who are unable or unwilling to take appropriate contraceptive measures;
Other uncontrollable diseases that may interfere with the research results, including but not limited to infection, hypertension, diabetes, cardiovascular and cerebrovascular diseases, etc;
There are situations that may increase the risk of participating in experiments or research product use, such as liver enzyme elevation exceeding twice the normal upper limit and/or GFR<60 mL/min/1.73 m2;
Have a history of drug abuse, alcohol dependence, or smoking within one month;
Patients with status epilepticus within one month;
Have potential progressive nervous system disease, such as encephalitis, brain tumor, multiple sclerosis or dementia;
Patients who plan to undergo epilepsy surgery within six months;
Patients with abnormal or diseased nasal structures;
Patients with cerebrospinal fluid rhinorrhea;
Patients whose family members have not been able to proficiently and correctly master the nasal drip method through standardized training
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xue Zhao
Phone
+8601069154786
Email
zhaoxue_pumch@sina.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaohong Han
Organizational Affiliation
Peking Union Medical College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yang Zhang
Phone
+8601069154126
12. IPD Sharing Statement
Learn more about this trial
Induced Pluripotent Stem Cell Derived Exosomes Nasal Drops for the Treatment of Refractory Focal Epilepsy
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