Clinical trial NCT05886205: 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
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Refractory Focal Epilepsy
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Guidon Pharmaceutics Ltd.
First posted: 2023-06-02
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Before conducting this study, understand and sign the informed consent form and comply with the requirements of this study;
2. The subjects are patients with focal epilepsy aged 18 to 70 years (inclusive), regardless of gender;
3. The subjects must comply with the definition of drug resistant epilepsy (ILAE);
4. 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;
5. Throughout the entire research process, the subject/legal guardian must be able to accurately record the log of epileptic seizures;
6. Subjects must experience at least 4 countable seizures within 28 days prior to the screening period;
7. The subjects are willing and able to comply with the research requirements.

Exclusion Criteria:

1. Unwilling or unable to follow the procedures stipulated in the agreement;
2. Pregnant or lactating women, or women with reproductive potential who are unable or unwilling to take appropriate contraceptive measures;
3. Other uncontrollable diseases that may interfere with the research results, including but not limited to infection, hypertension, diabetes, cardiovascular and cerebrovascular diseases, etc;
4. 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;
5. Have a history of drug abuse, alcohol dependence, or smoking within one month;
6. Patients with status epilepticus within one month;
7. Have potential progressive nervous system disease, such as encephalitis, brain tumor, multiple sclerosis or dementia;
8. Patients who plan to undergo epilepsy surgery within six months;
9. Patients with abnormal or diseased nasal structures;
10. Patients with cerebrospinal fluid rhinorrhea;
11. Patients whose family members have not been able to proficiently and correctly master the nasal drip method through standardized training

Primary outcomes:
measure: adverse events as assessed by CTCAE
timeFrame: 24 weeks from post-administration
Secondary outcomes:
measure: Number of participants with abnormal vital signs and abnormal Physical examination findings
timeFrame: Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
measure: Number of participants with abnormal Neurological examination
timeFrame: Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
measure: Number of participants with abnormal laboratory tests results
timeFrame: Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
measure: Number of participants with abnormal Urine analysis
timeFrame: Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
measure: Seizures frequency
timeFrame: before administration; administration; after the first administration 1 week,2 weeks,4 weeks,8 weeks,12 weeks,16 weeks,24 weeks
measure: Scalp electroencephalogram monitoring
timeFrame: Screening, after the first administration 12 weeks
measure: Head magnetic resonance imaging (MRI) examination
timeFrame: Screening, after the first administration 12 weeks
Other outcomes:
measure: Exploratory research-1
timeFrame: Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
measure: Exploratory research-2
timeFrame: Screening, after the first administration 1 week, 2 weeks, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 24 weeks
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Xiaohong Han
role: PRINCIPAL_INVESTIGATOR
References: