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Name:
UMIN ID:

Recruitment status Enrolling by invitation
Unique ID issued by UMIN UMIN000036295
Receipt No. R000041294
Scientific Title Phase 1 Dose Escalation Study of Bosutinib in Patients with Amyotrophic Lateral Sclerosis (ALS)
Date of disclosure of the study information 2019/03/26
Last modified on 2019/06/11

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Basic information
Public title Phase 1 Dose Escalation Study of Bosutinib in Patients with Amyotrophic Lateral Sclerosis (ALS)
Acronym 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)
Scientific Title:Acronym Phase 1 Dose Escalation Study of Bosutinib in Patients with Amyotrophic Lateral Sclerosis (ALS)
Region
Japan

Condition
Condition Amyotrophic Lateral Sclerosis
Classification by specialty
Neurology
Classification by malignancy Others
Genomic information YES

Objectives
Narrative objectives1 To evaluate the safety and tolerability of bosutinib (100 mg/day, 200 mg/day, 300 mg/day, or 400 mg/day) to determine the maximum tolerated dose (MTD) and a recommended phase 2 dose (RP2D) of bosutinib for treatment of ALS patients.
Basic objectives2 Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase Phase I

Assessment
Primary outcomes Dose limiting toxicity (DLT) for 4 weeks after initiating bosutinib and during all treatment period (12 weeks).
Key secondary outcomes 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.

Base
Study type Interventional

Study design
Basic design Single arm
Randomization Non-randomized
Randomization unit
Blinding Open -no one is blinded
Control Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms 1
Purpose of intervention Treatment
Type of intervention
Medicine
Interventions/Control_1 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.
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit
20 years-old <=
Age-upper limit
80 years-old >
Gender Male and Female
Key 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.
Key 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 anticoagulation or related oral 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.
Target sample size 24

Research contact person
Name of lead principal investigator
1st name Haruhisa
Middle name
Last name Inoue
Organization Kyoto University
Division name Center for iPS Cell Research and Application
Zip code 606-8507
Address 53 kawahara-cho, Shogoin, Sakyo-ku, Kyoto
TEL 075-366-7360
Email prj-als_bosutinib@cira.kyoto-u.ac.jp

Public contact
Name of contact person
1st name Keiko
Middle name
Last name Imamura
Organization Kyoto University
Division name Center for iPS Cell Research and Application
Zip code 606-8507
Address 53 kawahara-cho, Shogoin, Sakyo-ku, Kyoto
TEL 075-366-7360
Homepage URL
Email prj-als_bosutinib@cira.kyoto-u.ac.jp

Sponsor
Institute Center for iPS Cell Research and Application, Kyoto University
Institute
Department

Funding Source
Organization Japan Agency for Medical Research and Development (AMED)
Organization
Division
Category of Funding Organization Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor Provider of the investigational product: Pfizer Japan Inc.
Name of secondary funder(s)

IRB Contact (For public release)
Organization -
Address -
Tel -
Email -

Secondary IDs
Secondary IDs NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions 京都大学医学部附属病院(京都府)、徳島大学病院(徳島県)、北里大学病院(神奈川県)、鳥取大学医学部附属病院(鳥取県)

Other administrative information
Date of disclosure of the study information
2019 Year 03 Month 26 Day

Related information
URL releasing protocol
Publication of results Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status Enrolling by invitation
Date of protocol fixation
2019 Year 01 Month 22 Day
Date of IRB
2019 Year 02 Month 28 Day
Anticipated trial start date
2019 Year 03 Month 29 Day
Last follow-up date
2021 Year 01 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date
2019 Year 03 Month 26 Day
Last modified on
2019 Year 06 Month 11 Day


Link to view the page
URL(English) https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041294

Research Plan
Registered date File name

Research case data specifications
Registered date File name

Research case data
Registered date File name


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