EPI-589 Early Phase 2 Investigator-initiated Clinical trial for ALS

JRCT ID: jRCT2061210031

Registered date:27/08/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Amyotrophic Lateral Sclerosis
• Date of first enrollment: 04/10/2021
• Target sample size: 10
• Study type: Interventional
• Intervention(s): EPI-589 500 mg (2 tablets of EPI-589 250 mg) is orally administered three times a day before meals (at least one hour before breakfast, lunch, and dinner). The treatment period will be from the day after the registration of the treatment period to the end of the examination at 24 weeks of the treatment period.

Outcome(s)

Primary Outcome

Safety and tolerability
Adverse events (AEs), laboratory tests, vital signs, 12-lead electrocardiogram (ECG), and Columbia-Suicide Severity Rating Scale (C-SSRS)

Secondary Outcome

1) Efficacy
Change and percent change in ALSFRS-R score, time to event (whole-day use of noninvasive respiratory support, use of invasive respiratory support, or death) from the start day of the treatment phase, change in Slow Vital Capacity (%SVC), change in Manual Muscle Testing (MMT) total score, change in grip strength (right and left) , change in Modified Norris Scale total score, and change in ALS assessment questionnaire-40 (ALSAQ-40) total score
2) Biomarkers
Changes in CSF biomarkers (3-nitrotyrosine [3-NT], 8-hydroxy-2'-deoxyguanosine [8-OHdG], ornithine, phosphorylated neurofilament heavy chain [pNfH], neurofilament light chain [NfL]), changes in plasma biomarkers (3-NT, 8-OHdG, pNfH, NfL, creatinine), change in blood homocysteine level, change in N-acetylaspartate (NAA) (corrected for creatine, choline, and creatine + choline) measured by proton magnetic resonance spectroscopy (1H-MRS), changes in DTI-derived fractional anisotropy and apparent diffusion coefficient, and analysis of whole-brain 3D T1-weighted image

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 79age old
• Gender: Both

Include criteria

(1) subjects providing written informed consent (Subject and representative providing written informed conset are needed, if the subject is under 20 years old.)
(2) aged between 18 and 79 years at the time of informed consent
(3) meet the revised El Escorial criteria for clinically definite, clinically probable laboratory-supported or clinically probable
(4) within 18 months from symptom onset at screening
(5) ALSFRS-R total score progression of <-0.3 (>0.3 decline)/month between the onset and screening
(If ALSFRS-R at the time of symptom onset is not determined, please set as 48 points)
*progression rate is calculated as: (ALSFRS-R at the time of screening - ALSFRS-R at the time of onset)/duration from onset to screening (month).
(6) scores of >=2 points on all 12 items of ALSFRS-R

(7) scores of 4 points on three items of respiratory subscore of ALSFRS-R
(8) scores of >=3 points in ALSFRS-R swallowing item
(9) slow vital capacity (SVC) >= 80%
(10) on a stable dose of riluzole for at least 30 day prior to registration for pre-observation period
(11) ambulant
(12) agreement for genetic research

Exclude criteria

(1) with a complication or history of significant other medical conditions based on the investigator's judgement
(2) complications of psychological disease, cognitive impairment, or Parkinson's disease
(3) underwent tracheostomy
(4) with experience of using invasive or noninvasive positive pressure ventilation
(5) complications or history of drug allergy or severe allergic disease such as anaphylactic shock
(6) malignancy within past five years at the time of informed consent
(7) contraindications for lumbar puncture at screening
(8) contraindications for MRI including Magnetic Resonance Spectroscopy and Difusion Tensor Imaging at screening
(9) AST and ALT CK greater than 3 times upper limit of normal at screening
(10) CK greater than 2.5 times upper limit of normal at screening
(11) eGFR lower than 45 ml/min/1.73m^2 at screening
(12) pregnant, nursing, or plan to get pregnant during the course of this clinical trial at screening
(13) childbearing potential, or unwilling to use accepted methods of contraception
(14) use of edaravone within 30 days from the start of pre-observation period
(15) change the dosage or discontinuation of riluzole after informed consent
(16) history of administration of EPI-589
(17) participation in a clinical trial before informed consent and within 30 days from investigational drug administration (If 5 times of the investigational drug half life is longer than 30 days, it should takes longer times than 5 times of the investigational drug half life) or willingness to participate for other clinical trial at the time of informed consent
(18) history of cell therapy or gene therapy before infromed consent
(19) ineligible for the clinical trial based on the investigator's judgement

Related Information

• Primary Sponsor: Fujita Koji
• Source(s) of Monetary Support: Sumitomo Pharma Co.,Ltd.