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Safety of EPI-589 re-administration for amyotrophic lateral sclerosis

Safety of EPI-589 re-administration for ALS

1

63 years old, male, diagnosed with Clinical probable ALS (date of onset May 31, 2021), severity of ALS degree 3, initial symptom was upper limb type.

This study was conducted as the Patient-proposed Health Services to evaluate the safety and tolerability of retreatment with EPI-589 in ALS patients who had received EPI-589 in a previous investigator-initiated clinical trial. One case was enrolled during enrollment period, and protocol treatment was completed.

No adverse events occurred.

[Primary endpoint: adverse events] No adverse events were observed. [Secondary endpoints] 1. ALSFRS-R score change and rate of change As shown below, there was no suppression of ALSFRS-R score deterioration during the treatment period compared to that prior to the treatment. - The total score was 33 at screening and gradually decreased during follow-up to 19 at 22 weeks of treatment (score change -14, rate of change -42.4%). - The sub-domain score for Bulbar was 12 at screening and 8 at 22 weeks of treatment (score change -4, rate of change -33.3%), Fine motor was 2 at screening and 0 at 22 weeks of treatment (score change -2, rate of change -100%), Gross motor was 7 at screening and 3 points at 22 weeks of treatment (score change -4, rate of change -57.1%), and Respiratory was 12 points at screening and 8 points at 22 weeks of treatment (score change -4, rate of change -33.3%). 2. Time from the start of the treatment period to the occurrence of an event (full-day use of noninvasive respiratory support, use of invasive respiratory support, or death) These events did not occur. 3. Change in %SVC 50.1 at screening, 34.8 (change -15.3) after 12 weeks of treatment, and 28.6 (change -21.5) after 22 weeks of treatment.

There were no safety or tolerability issues. The patient was considered a responder in the previous study. But, efficacy in this study was not clear as a worsening of the ALSFRS-R score was observed during the treatment. The reason for this may be the suppressive effect of the drug became less effective as the disease stage progressed. In future drug development for ALS, it is necessary to establish a diagnostic method in the early stage and to provide treatment as early as possible after diagnosis.

May. 23, 2024

No

NA

https://jrct.niph.go.jp/latest-detail/jRCTs051230064

Nagano Seiichi

Osaka University Hospital

2-15 Yamadaoka, Suita, Osaka

nagano@neurol.med.osaka-u.ac.jp

Nagano Seiichi

Osaka University Hospital

2-15 Yamadaoka, Suita, Osaka

+81-6-6879-5111

nagano@neurol.med.osaka-u.ac.jp

Complete

July. 06, 2023

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1) Patients who have given written informed consent to participate in this clinical study (or patients for whom a signature was obtained by a proxy, in case patients who have the ability to consent but are unable to sign the consent form in their own handwriting due to physical disabilities).
2) Patients who have entered the investigator-initiated clinical trial (DA350103) and have received EPI-589 for about 24 weeks, and have had no concerns with safety or tolerability.
3) Patients who can go to outpatient clinic

1) Patients who have clinically significant complications or medical history other than ALS, and who are judged to be inappropriate for clinical study by the investigator.
2) Patients with psychiatric disorders, cognitive impairment, or Parkinson's disease.
3) Patients undergoing tracheostomy.
4) Patients wearing a non-invasive respiratory support device all day (wearing for 22 hours or more).
5) Patients with a history of or complication of drug allergy or severe allergic disease (anaphylactic shock, etc.).
6) Patients who have a malignant tumor or have a medical history within 5 years before obtaining informed consent.
7) Patients whose AST and ALT levels were 3 times or more higher than the upper limit of normal at the time of screening.
8) Patients with CK =>2.5 times the upper limit of normal at screening.
9) Patients with estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73m2 at screening.
10) Pregnant women, lactating women, or patients who may be pregnant.
11) Patients or their partners wish to become pregnant, or patients who cannot agree to practice contraception during the period from the time of obtaining informed consent to 30 days after the last dose of the study drug.
12) Patients who participated in a clinical trial other than the investigator-initiated trial (DA350103) before consent was obtained, and 30 days had not passed since the administration of the test drug in the same clinical trial at the time of consent (half-life of the test drug in the same clinical trial If the number of days multiplied by 5 is longer than 30 days, the number of days 5 times the half-life must have passed), or patients participating or plan to participate in a clinical trial other than the investigator-initiated trial (DA350103) at the time of obtaining consent.
13) Patients who received cell therapy or gene therapy before obtaining informed consent.
14) Patients who are judged inappropriate for participation in this clinical study by the investigator.

Both

Amyotrophic lateral sclerosis

Administer EPI-589 500 mg orally three times daily before meals. The administration period will be from the day after registration of the treatment period to the end of all examinations and observations specified at the 22nd week of the treatment period.

Adverse events

Amount and rate of change in ALSFRS-R score
Period from start of treatment period to occurrence of event (all-day use of noninvasive respiratory support device, use of invasive respiratory support device, or death)
Amount of change in %SVC
Clinical examination
Vital signs
Body weight

+81-6-6210-8296

May. 02, 2023

none