Ignite Creation Date:
2024-05-06 @ 3:45 PM
Last Modification Date:
2024-10-26 @ 1:56 PM
Study NCT ID:
NCT04744532
Status:
RECRUITING
Last Update Posted:
2023-03-08
First Post:
2021-01-09
Brief Title:
iPSC-based Drug Repurposing for ALS Medicine iDReAM Study
Sponsor:
Kyoto University
Organization:
Kyoto University Hospital
Study Overview
Official Title:
Phase 12 Study of Bosutinib in Patients With Amyotrophic Lateral Sclerosis ALS
Status:
RECRUITING
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study consists of a phase 1 part and a phase 2 part
Phase 1 part
This is a phase 1 open-label multicenter dose escalation study to evaluate the safety and tolerability of bosutinib to determine the maximum tolerated doseMTD and a recommended phase 2 dose RP2D of bosutinib for treatment of ALS patients Also efficacy will be evaluated exploratory
Phase 2 part
This is an open label multicenter phase 2 part whose purpose is to evaluate the efficacy exploratorily and the long-term for 24 weeks safety of bosutinib for the treatment of ALS patients
Phase 1 part
This is a phase 1 open-label multicenter dose escalation study to evaluate the safety and tolerability of bosutinib to determine the maximum tolerated doseMTD and a recommended phase 2 dose RP2D of bosutinib for treatment of ALS patients Also efficacy will be evaluated exploratory
Phase 2 part
This is an open label multicenter phase 2 part whose purpose is to evaluate the efficacy exploratorily and the long-term for 24 weeks safety of bosutinib for the treatment of ALS patients
Detailed Description:
Phase 1 part
The study consists of a 12-week observation period a 1-week acceptable window 5-9 days transitional period a 12-week study treatment period and a 4-week follow-up period Subjects who have been receiving riluzole since before the enrollment are allowed to continuously receive riluzole during the 12-week observation period with the dosage remaining unchanged and stop receiving riluzole from the beginning of the 1-week acceptable window 5-9 days transitional period After the completion of the transitional period subjects whose total ALSFRS-R score decreased by 1 to 3 points during the 12-week observation period will receive bosutinib for 12 weeks to evaluate the safety and tolerability of bosutinib in ALS patients All ALS drugs including riluzole will be prohibited during the bosutinib treatment period
In this study 3 to 6 ALS patients will be enrolled in each of the 4 bosutinib dose lelvels 100 mgday dose level 1 200 mgday dose level 2 300 mgday dose level 3 or 400mgday dose level 4 to evaluate the safety and tolerability of the investigational drug bosutinib under a 33 dose escalation study design The dose will be escalated by 1 dose level at a time no skipping will be allowed
Dose escalation and MTD will be determined by the safety assessment committee comprising oncologist hematologist ALS Expert based on the incidence of DLT in 4 weeks of treatment among 3 subjects enrolled 6 subjects if additionaly enrolled in each dose level RP2D will be determined by the safety assessment committee upon completion of 12-week study treatment in all subjects in all dose levels
Phase 2 part
The phase 2 part consists of 4 periods including a 12-week observation period a 1-week 2 days transitional period a 24-week study treatment period and a 4-week safety follow-up period After the completion of the transitional period subjects whose total ALSFRS-R score decreased by 1 to 4 points during the 12-week observation period will receive bosutinib treatment during the 24-week study treatment period
In this study 25 ALS patients will be enrolled patients will be randomly assigned to the following groups 12 patients in 200 mgday group and 13 patients in 300 mgdaygroup of the investigational drug bosutinib The efficacy and the safety of bosutinib in ALS patients for 24 weeks will be assessed The efficacy using ALSFRS-R score will be also compared with the external published data from edaravone study MCI186-19 In order to compare with the edaravone study MCI186-19 the eligibility criteria of the phase 2 part is similar to those in MCI186-19 By statical allocation approximately 85 of patients in each 200 mg and 300 mg group will have a decrease of 1-2 points in ALSFRS-R and 15 will have a decrease of 3-4 points in ALSFRS-R during the observation period in accordance with MCI186-19
The efficacy using ALSFRS-R score will be also compared with matched control of Japanese Consorsium for Amyotrophic Lateral Sclerosis JaCALS a registory of ALS in an exploratory manner
The study consists of a 12-week observation period a 1-week acceptable window 5-9 days transitional period a 12-week study treatment period and a 4-week follow-up period Subjects who have been receiving riluzole since before the enrollment are allowed to continuously receive riluzole during the 12-week observation period with the dosage remaining unchanged and stop receiving riluzole from the beginning of the 1-week acceptable window 5-9 days transitional period After the completion of the transitional period subjects whose total ALSFRS-R score decreased by 1 to 3 points during the 12-week observation period will receive bosutinib for 12 weeks to evaluate the safety and tolerability of bosutinib in ALS patients All ALS drugs including riluzole will be prohibited during the bosutinib treatment period
In this study 3 to 6 ALS patients will be enrolled in each of the 4 bosutinib dose lelvels 100 mgday dose level 1 200 mgday dose level 2 300 mgday dose level 3 or 400mgday dose level 4 to evaluate the safety and tolerability of the investigational drug bosutinib under a 33 dose escalation study design The dose will be escalated by 1 dose level at a time no skipping will be allowed
Dose escalation and MTD will be determined by the safety assessment committee comprising oncologist hematologist ALS Expert based on the incidence of DLT in 4 weeks of treatment among 3 subjects enrolled 6 subjects if additionaly enrolled in each dose level RP2D will be determined by the safety assessment committee upon completion of 12-week study treatment in all subjects in all dose levels
Phase 2 part
The phase 2 part consists of 4 periods including a 12-week observation period a 1-week 2 days transitional period a 24-week study treatment period and a 4-week safety follow-up period After the completion of the transitional period subjects whose total ALSFRS-R score decreased by 1 to 4 points during the 12-week observation period will receive bosutinib treatment during the 24-week study treatment period
In this study 25 ALS patients will be enrolled patients will be randomly assigned to the following groups 12 patients in 200 mgday group and 13 patients in 300 mgdaygroup of the investigational drug bosutinib The efficacy and the safety of bosutinib in ALS patients for 24 weeks will be assessed The efficacy using ALSFRS-R score will be also compared with the external published data from edaravone study MCI186-19 In order to compare with the edaravone study MCI186-19 the eligibility criteria of the phase 2 part is similar to those in MCI186-19 By statical allocation approximately 85 of patients in each 200 mg and 300 mg group will have a decrease of 1-2 points in ALSFRS-R and 15 will have a decrease of 3-4 points in ALSFRS-R during the observation period in accordance with MCI186-19
The efficacy using ALSFRS-R score will be also compared with matched control of Japanese Consorsium for Amyotrophic Lateral Sclerosis JaCALS a registory of ALS in an exploratory manner
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None