UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000036295
Receipt number 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 2021/09/22 22:33:22

* This page includes information on clinical trials registered in UMIN clinical trial registed system.
* We don't aim to advertise certain products or treatments


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 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.

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 or person

Institute

Center for iPS Cell Research and Application, Kyoto University

Institute

Department

Personal name



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

13

Results

The number of enrollments.
100 mg/day: 3 patients
200 mg/day: 3 patients
300 mg/day: 4 patients (early termination: 1)
400 mg/day: 3 patients
The safety and tolerability of the investigational drug (bosutinib) were evaluated and determined the maximum tolerated dose (MTD) and a recommended phase 2 dose (RP2D) of bosutinib for treatment of ALS patients.

Results date posted

2021 Year 09 Month 22 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

Patients with change in total ALSFRS-R score during the observation period are -1 to
-3 points

Participant flow


Adverse events

Nothing to particular

Outcome measures


Plan to share IPD

-

IPD sharing Plan description

-


Progress

Recruitment status

Completed

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 05 Month 31 Day

Date of closure to data entry

2021 Year 09 Month 22 Day

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

2021 Year 09 Month 22 Day



Link to view the page

Value
https://center6.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