Amyotrophic Lateral Sclerosis
Conditions
Interventions
The study consists of a 12-week observation period, a 1-week (5- to 9-day) transitional period, a 12-week study treatment period, and a 4-week follow-up period. 3 to 6 ALS patients will be enrolled
Sponsors
Center for iPS Cell Research and Application, Kyoto University
Provider of the investigational product: Pfizer Japan Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study. To be additionally signed by a delegate signer if the subject is unable to handwrite. 2. Patients with positive already-reported SOD1 gene mutation and progressive muscle weakness; sporadic ALS patients who are categorized as either 'Definite ALS' or 'Probable ALS' or 'Probable-laboratory supported ALS' in the Updated Awaji Criteria for the diagnosis of ALS 3. Patients at Grade 1 or 2 in the Japan ALS Severity Scale of the grant-in-aid program for chronic diseases from the Japanese Ministry of Health, Labour and Welfare; patients with positive SOD1 mutation of Grade 1, 2 or 3 4. Patients with ALS that occurred within 2 years at the time of the first registration; patients with positive SOD1 mutation within 5 years after disease onset 5. Patients who can visit hospital regularly as outpatients 6. Patients with change in total ALSFRS-R score during the observation period are -1 to -3 points 7. Urine pregnancy test (for females of childbearing potential) negative at screening 8. Patients with appropriate renal function at the time of the first and second registrations 9. Patients with appropriate hepatic function at the time of the first and second registrations 10. Able to take oral tablets etc.
Exclusion criteria
Exclusion criteria: 1. Patients with tracheostomy 2. Patients who have used non-invasive ventilation due to ALS symptoms 3. Patients whose %FVCs are less than 70% at the time of first and second registrations 4. Patients who have nerve conduction study findings of demyelination such as conduction block 5. Patients who are taking edaravone; patients who started riluzole or edaravone after start of the observation period; patients who changed the dosage of riluzole after start of the observation period 6. Patients with bulbar type ALS with dysphagia and dysarthria 7. Patients with cognitive impairment 8. Pregnant female patients; breastfeeding female patients; fertile male and female patients of childbearing potential who are unwilling or unable to use 1 highly effective methods for the duration of the study and for at least 28 days after the last dose of investigational product 9. History of clinically significant or uncontrolled cardiac disease including 10. Uncontrolled hypomagnesemia or uncorrected hypokalemia due to potential effects on the QT interval 11.Patient who is taking the following medicines during study drugs administration. -Combination of warfarin or other anticoagulation. -Src or c-Abl inhibitors -Drugs known to prolong the QT interval or predispose to Torsades de Pointe -Current or anticipated use of a strong or moderate CYP3A inhibitor and inducer -Drugs affecting gastric pH such as Proton pump inhibitors 12.History of malignancy within 5 years prior to registration 13. Known prior or suspected severe hypersensitivity to study drugs or any component in their formulations 14. Patients with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness 15. Recent or ongoing clinically significant GI disorder 16. Patients with chronic obstructive pulmonary disease etc.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limiting toxicity (DLT) for 4 weeks after initiating bosutinib and during all treatment period (12 weeks). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoint(s): Adverse events (AEs), laboratory abnormality, vital signs (blood pressure, pulse rate, body temperature), electrocardiogram (ECG), chest X-ray findings AEs will be graded according to the Common Terminology Criteria for Adverse Events ver. 4.03 (CTCAE v.4.03). Exploratory Endpoints: Changes from baseline in total ALSFRS-R score, %FVC and grip strength. Changes in blood neurofilament L and phosphorylated neurofilament H during the observation period and the study treatment period. | — |
Countries
Japan
Contacts
Public ContactKeiko Imamura
Kyoto University Center for iPS Cell Research and Application
Outcome results
None listed