Phase 1 Dose Escalation Study of Bosutinib in Patients with Amyotrophic Lateral Sclerosis (ALS)

• Register: JPRN
• Last refreshed on: 17 October 2023
• Main ID: JPRN-UMIN000036295
• Date of registration: 26/03/2019
• Prospective Registration: Yes
• Primary sponsor: Center for iPS Cell Research and Application, Kyoto University
• Public title: Phase 1 Dose Escalation Study of Bosutinib in Patients with Amyotrophic Lateral Sclerosis (ALS)
• Scientific title: Phase 1 Dose Escalation Study of Bosutinib in Patients with Amyotrophic Lateral Sclerosis (ALS) - Phase 1 Dose Escalation Study of Bosutinib in Patients with Amyotrophic Lateral Sclerosis (ALS)
• Date of first enrolment: 2019/03/29
• Target sample size: 24
• Recruitment status: Complete: follow-up complete
• URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041294
• Study type: Interventional
• Study design: Single arm Non-randomized
• Phase: Phase I

Countries of recruitment

Japan

Contacts

• Name: Haruhisa Inoue
• Affiliation: Kyoto University Center for iPS Cell Research and Application

• Name: Keiko Imamura
• Affiliation: Kyoto University Center for iPS Cell Research and Application

Key inclusion & exclusion criteria

Inclusion 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.

Age minimum: 20years-old
Age maximum: 80years-old
Gender: Male and Female

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis

Intervention(s)

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 in each of the 4 bosutinib dose levels [100 mg/day (dose level 1), 200 mg/day (dose level 2), 300 mg/day (dose level 3), or 400mg/day (dose level 4)] to evaluate the safety and tolerability of the investigational drug (bosutinib) under a 3+3 dose escalation study design.

Primary Outcome(s)

Dose limiting toxicity (DLT) for 4 weeks after initiating bosutinib and during all treatment period (12 weeks).

Secondary Outcome(s)

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.

Source(s) of Monetary Support

Japan Agency for Medical Research and Development (AMED)

Secondary Sponsor(s)

Provider of the investigational product: Pfizer Japan Inc.

Ethics review

Status: YES
Approval date: 28/02/2019
Contact:

-

-

-

-

Results

• Results available: Yes
• Date Posted: 22/09/2021
• Date Completed: 31/05/2021