iPSC-based Drug Repurposing for ALS Medicine (iDReAM) Study

• Register: ClinicalTrials.gov
• Last refreshed on: 13 March 2023
• Main ID: NCT04744532
• Date of registration: 09/01/2021
• Prospective Registration: No
• Primary sponsor: Kyoto University
• Public title: iPSC-based Drug Repurposing for ALS Medicine (iDReAM) Study
• Scientific title: Phase 1/2 Study of Bosutinib in Patients With Amyotrophic Lateral Sclerosis (ALS)
• Date of first enrolment: March 19, 2019
• Target sample size: 49
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/show/NCT04744532
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Japan

Contacts

• Name: Haruhisa Inoue
• Affiliation: Kyoto University

• Name: Haruhisa Inoue

Key inclusion & exclusion criteria

[Phase 1 part]

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 additionaly
signed by a delegate signer if the subject is unable to handwrite.

2. Patients aged =20 years and <80 years at the time of informed consent

3. 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

4. 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

5. 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

6. Patients who can visit hospital regularly as outpatients

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

8. Urine pregnancy test (for females of childbearing potential) negative at screening

Female patients of nonchildbearing potential must meet at least 1 of the following
criteria:

1. Achieved postmenopausal status, defined as follows: cessation of regular menses
for at least 12 consecutive months with no alternative pathological or
physiological cause; status may be confirmed with a serum follicle stimulating
hormone (FSH) level confirming the postmenopausal state;

2. Have undergone a documented hysterectomy and/or bilateral oophorectomy;

3. Have medically confirmed ovarian failure. All other female patients (including
female patients with tubal ligations) are considered to be of childbearing
potential.

Male and female patients of childbearing potential must agree to use one highly
effective method of contraception as outlined in this protocol, throughout the study
and for at least 28 days after the last dose of investigational product.

9. Patients with appropriate renal function as defined as follows at the time of the
first and second registrations

a. Serum creatinine =1.5 × upper limit of normal (ULN) or estimated creatinine
clearance =60 mL/min as calculated using the method standard for the institution.

10. Patients with appropriate hepatic function as defined as follows at the time of the
first and second registrations b. Total serum bilirubin =1.5 × ULN unless the patient
has documented Gilbert syndrome; c. AST and ALT =2.5 × ULN

11. Able to take oral tablets

12. Patients whose acute effect of previous treatment has recovered to the baseline or
CTCAE v.4.03 = Grade 1 at the time of the first and second registrations

13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures

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 of contraception as outlined in this protocol 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:

- History of, or active, congestive heart failure;

- Uncontrolled angina or hypertension within 3 months prior to registration;

- Myocardial infarction within 12 months prior to registration;

- Clinically significant ventricular arrhythmia (such as ventricular tachycardia,
ventricular fibrillation, or Torsades de pointes);

- Diagnosed or suspected congenital or acquired prolonged QT interval history or
prolonged QTc (QTcF should not exceed 500 msec);

- Unexplained syncope

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.

a Combination of warfarin or other anticoagulation. Combination of therapeutic
anticoagulant therapy with low molecular weight heparin is acceptable b Src or c-Abl
inhibitors c Other treatments for cancer d Drugs known to prolong the QT interval or
predispose to Torsades de Pointe e Current or anticipated use of a strong or moderate
CYP3A inhibitor and inducer f Drugs affecting gastric pH such as Proton pump
inhibitors (e.g., lansoprazole)

12. History of malignancy within 5 years prior to registration with the exception of basal
cell carcinoma or cervical carcinoma in situ or Stage 1 or 2 cancer that is considered
adequately treated and currently in complete remission for at least 12 months

13. Patients who were enrolled in other clinical study within 12 weeks before the first
registration, or are expected to be enrolled in other clinical study using a study
drug during this study

14. Known prior or suspected severe hypersensitivity to study drugs or any component in
their formulations

15. 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

16. Recent or ongoing clinically significant GI disorder (eg, Crohn's disease, ulcerative
colitis, or prior total or partial gastrectomy).

17. Patients with chronic obstructive pulmonary disease

18. Major surgery or radiotherapy within 14 days prior to registration at the time of the
first registration

19. Patient who fulfills the conditions:

1. Neutroph


Age minimum: 20 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Amyotrophic Lateral Sclerosis

Intervention(s)

Drug: Bosutinib (Phase 1 part)

Drug: Bosutinib (Phase 2 part)

Primary Outcome(s)

Phase 1 part: Dose-limiting toxicity (DLT) [Time Frame: During the first 4 weeks of treatment with bosutinib]

Phase 1 part: Dose-limiting toxicity (DLT) [Time Frame: Up to 12 weeks of treatment with bosutinib]

Phase 2 part: Adverse events [Time Frame: Up to 24 weeks of treatment with bosutinib]

Phase 2 part: Incidence of abnormal ECG recordings [Time Frame: Up to 24 weeks of treatment with bosutinib]

Phase 2 part: Incidence of abnormal laboratory test results [Time Frame: Up to 24 weeks of treatment with bosutinib]

Phase 2 part: Incidence of abnormal vital signs [Time Frame: Up to 24 weeks of treatment with bosutinib]

Phase 2 part: Incidence of abnormal X-ray findings [Time Frame: Up to 24 weeks of treatment with bosutinib]

Phase 2 part: Change in ALSFRS-R from baseline to week 24 in each 200mg and 300mg group compared with the external published data of placebo group [Time Frame: Up to 24 weeks of treatment with bosutinib]

Secondary Outcome(s)

Phase 1 part: Incidence of abnormal ECG recordings [Time Frame: Up to 12 weeks of treatment with bosutinib]

Phase 1 part: Incidence of abnormal vital signs [Time Frame: Up to 12 weeks of treatment with bosutinib]

Phase 1 part: Incidence of abnormal laboratory test results [Time Frame: Up to 12 weeks of treatment with bosutinib]

Phase 1 part: Incidence of abnormal X-ray findings [Time Frame: Up to 12 weeks of treatment with bosutinib]

Phase 1 part: Adverse events [Time Frame: Up to 12 weeks of treatment with bosutinib]

Phase 2 part: Change in ALSFRS-R from baseline to week 24 in combined group of 200 mg and 300 mg group compared with edaravone group [Time Frame: Up to 24 weeks of treatment with bosutinib]

Phase 2 part: Change in ALSFRS-R from baseline to week 24 in combined group of 200 mg and 300 mg group compared with placebo group [Time Frame: Up to 24 weeks of treatment with bosutinib]

Secondary ID(s)

WI240618

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Tokushima University

Tottori University

Nara Medical University

Toho University

Hiroshima University

Kitasato University

Pfizer