Trial Outcomes & Findings for A Study Comparing Ponatinib and Nilotinib in Participants With Chronic Myeloid Leukemia (NCT NCT02627677)

Last Updated: 2021-11-26

Results Overview

MMR is defined as the percentage of participants achieving a ratio of ≤0.1% Breakpoint Cluster Region-Abelson (BCR ABL) to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL\[IS\]) at any time within 12 months after randomization.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

44 participants

Primary outcome timeframe

Up to 12 months

Results posted on

2021-11-26

Participant Flow

Participants took part in the study at 90 investigative sites in Austria, Canada, Czechia, France, Hungary, Italy, Korea, and Russia from 31 December 2015 to 20 January 2021

Participants with a diagnosis of chronic phase-chronic myeloid leukemia were enrolled and randomised at a ratio of 1:2:1 to receive ponatinib 30 mg and ponatinib 15 mg compared with nilotinib 400 mg.

Participant milestones

Participant milestones
Measure	Cohort A: Ponatinib 30 mg Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Overall Study STARTED	11	21	12
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	11	21	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: Ponatinib 30 mg Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Overall Study Adverse event (not progressive disease)	1	4	1
Overall Study Progressive disease	1	3	0
Overall Study Lack of Efficacy	1	2	0
Overall Study Lost to Follow-up	0	0	1
Overall Study Pregnancy	0	1	0
Overall Study Study Terminated by Sponsor	5	10	6
Overall Study Physician Decision	0	0	2
Overall Study Withdrawal by Subject	2	1	1
Overall Study Reason not Specified	0	0	1
Overall Study Randomized but not Treated	1	0	0

Baseline Characteristics

Number analyzed is the number of participants with data available for Height at Baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=21 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=12 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.	Total n=43 Participants Total of all reporting groups
Age, Continuous	43.7 years STANDARD_DEVIATION 17.43 • n=10 Participants	44.7 years STANDARD_DEVIATION 15.53 • n=21 Participants	54.3 years STANDARD_DEVIATION 13.23 • n=12 Participants	47.16 years STANDARD_DEVIATION 15.69 • n=43 Participants
Sex: Female, Male Female	3 Participants n=10 Participants	11 Participants n=21 Participants	6 Participants n=12 Participants	20 Participants n=43 Participants
Sex: Female, Male Male	7 Participants n=10 Participants	10 Participants n=21 Participants	6 Participants n=12 Participants	23 Participants n=43 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=10 Participants	0 Participants n=21 Participants	1 Participants n=12 Participants	1 Participants n=43 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants n=10 Participants	21 Participants n=21 Participants	11 Participants n=12 Participants	42 Participants n=43 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants	0 Participants n=21 Participants	0 Participants n=12 Participants	0 Participants n=43 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants	0 Participants n=21 Participants	0 Participants n=12 Participants	0 Participants n=43 Participants
Race (NIH/OMB) Asian	2 Participants n=10 Participants	4 Participants n=21 Participants	1 Participants n=12 Participants	7 Participants n=43 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=21 Participants	0 Participants n=12 Participants	0 Participants n=43 Participants
Race (NIH/OMB) Black or African American	0 Participants n=10 Participants	0 Participants n=21 Participants	0 Participants n=12 Participants	0 Participants n=43 Participants
Race (NIH/OMB) White	7 Participants n=10 Participants	16 Participants n=21 Participants	10 Participants n=12 Participants	33 Participants n=43 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants	0 Participants n=21 Participants	0 Participants n=12 Participants	0 Participants n=43 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=10 Participants	1 Participants n=21 Participants	1 Participants n=12 Participants	3 Participants n=43 Participants
Region of Enrollment Austria	0 Participants n=10 Participants	1 Participants n=21 Participants	0 Participants n=12 Participants	1 Participants n=43 Participants
Region of Enrollment Canada	0 Participants n=10 Participants	0 Participants n=21 Participants	1 Participants n=12 Participants	1 Participants n=43 Participants
Region of Enrollment Czech Republic	0 Participants n=10 Participants	0 Participants n=21 Participants	2 Participants n=12 Participants	2 Participants n=43 Participants
Region of Enrollment France	1 Participants n=10 Participants	1 Participants n=21 Participants	1 Participants n=12 Participants	3 Participants n=43 Participants
Region of Enrollment Hungary	0 Participants n=10 Participants	1 Participants n=21 Participants	0 Participants n=12 Participants	1 Participants n=43 Participants
Region of Enrollment Italy	0 Participants n=10 Participants	0 Participants n=21 Participants	1 Participants n=12 Participants	1 Participants n=43 Participants
Region of Enrollment Korea, North	1 Participants n=10 Participants	2 Participants n=21 Participants	0 Participants n=12 Participants	3 Participants n=43 Participants
Region of Enrollment Russia	8 Participants n=10 Participants	16 Participants n=21 Participants	7 Participants n=12 Participants	31 Participants n=43 Participants
Height	172.9 cm STANDARD_DEVIATION 9.62 • n=10 Participants • Number analyzed is the number of participants with data available for Height at Baseline.	169.4 cm STANDARD_DEVIATION 9.35 • n=21 Participants • Number analyzed is the number of participants with data available for Height at Baseline.	168.8 cm STANDARD_DEVIATION 9.17 • n=11 Participants • Number analyzed is the number of participants with data available for Height at Baseline.	170.1 cm STANDARD_DEVIATION 9.28 • n=42 Participants • Number analyzed is the number of participants with data available for Height at Baseline.
Weight	77.50 kg STANDARD_DEVIATION 18.335 • n=10 Participants	72.72 kg STANDARD_DEVIATION 15.213 • n=21 Participants	70.94 kg STANDARD_DEVIATION 14.711 • n=12 Participants	73.34 kg STANDARD_DEVIATION 15.65 • n=43 Participants
Body Mass Index (BMI)	25.90 kg/m^2 STANDARD_DEVIATION 5.870 • n=10 Participants • Number analyzed is the number of participants with data available for BMI at Baseline.	25.35 kg/m^2 STANDARD_DEVIATION 4.974 • n=21 Participants • Number analyzed is the number of participants with data available for BMI at Baseline.	25.18 kg/m^2 STANDARD_DEVIATION 4.442 • n=11 Participants • Number analyzed is the number of participants with data available for BMI at Baseline.	25.44 kg/m^2 STANDARD_DEVIATION 4.95 • n=42 Participants • Number analyzed is the number of participants with data available for BMI at Baseline.

PRIMARY outcome

Timeframe: Up to 12 months

Population: Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=21 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=11 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Percentage of Participants With Major Molecular Response (MMR)	50.0 percentage of participants Interval 18.7 to 81.3	33.3 percentage of participants Interval 14.6 to 57.0	45.5 percentage of participants Interval 16.7 to 76.6

SECONDARY outcome

Timeframe: Up to 12 months

Population: Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.

MCyR was the percentage of participants achieving Complete cytogenetic response (CCyR: defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow) or Partial Cytogenetic Response (PCyR: defined as \>0% to 35% Ph+ metaphases by cytogenetic analysis of bone marrow) at any time within 12 months after randomization.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=20 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=12 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Percentage of Participants With Major Cytogenetic Response (MCyR)	50.0 percentage of participants Interval 18.7 to 81.3	60.0 percentage of participants Interval 36.1 to 80.9	50.0 percentage of participants Interval 21.1 to 78.9

SECONDARY outcome

Timeframe: Up to 12 months

Population: Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.

CCyR rate was defined as the percentage of participants achieving CCyR up to 12 months after randomization. CCyR is defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=20 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=12 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Percentage of Participants With Complete Cytogenetic Response (CCyR)	40.0 percentage of participants Interval 12.2 to 73.8	55.0 percentage of participants Interval 31.5 to 76.9	50.0 percentage of participants Interval 21.1 to 78.9

SECONDARY outcome

Timeframe: From Month 3 to every 3 months up to 48 months

Population: Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis. Number analyzed are participants with data available for analyses at given timepoint.

Molecular response rate is defined as percentage of participants achieving MR2: Molecular response with 2-log reduction (defined as ≤1% BCR-ABL\[IS\]), MMR: Major molecular responder, MR4 (defined as ≤0.01% BCR-ABL\[IS\]), and MR4.5 (defined as ≤0.0032% BCR-ABL\[IS\]) after randomization.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=21 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=12 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Percentage of Participants With Molecular Response (MR) MR2 - Month 3	70.0 percentage of participants	38.1 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 6	60.0 percentage of participants	57.1 percentage of participants	54.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 9	50.0 percentage of participants	52.4 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 12	50.0 percentage of participants	52.4 percentage of participants	54.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 15	50.0 percentage of participants	52.4 percentage of participants	54.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 18	50.0 percentage of participants	47.6 percentage of participants	54.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 21	50.0 percentage of participants	52.4 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 24	50.0 percentage of participants	47.6 percentage of participants	54.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 27	50.0 percentage of participants	42.9 percentage of participants	54.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 30	50.0 percentage of participants	38.1 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 33	30.0 percentage of participants	33.3 percentage of participants	27.3 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 36	50.0 percentage of participants	33.3 percentage of participants	36.4 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 39	20.0 percentage of participants	14.3 percentage of participants	18.2 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 42	10.0 percentage of participants	9.5 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 45	10.0 percentage of participants	14.3 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR2 - Month 48	10.0 percentage of participants	4.8 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 3	30.0 percentage of participants	4.8 percentage of participants	18.2 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 6	30.0 percentage of participants	28.6 percentage of participants	36.4 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 9	30.0 percentage of participants	28.6 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 12	40.0 percentage of participants	33.3 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 15	40.0 percentage of participants	28.6 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 18	40.0 percentage of participants	38.1 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 21	40.0 percentage of participants	33.3 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 24	40.0 percentage of participants	33.3 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 27	40.0 percentage of participants	33.3 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 30	40.0 percentage of participants	33.3 percentage of participants	45.5 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 33	20.0 percentage of participants	28.6 percentage of participants	27.3 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 36	40.0 percentage of participants	28.6 percentage of participants	36.4 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 39	20.0 percentage of participants	14.3 percentage of participants	18.2 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 42	10.0 percentage of participants	9.5 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 45	10.0 percentage of participants	9.5 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR3/MMR - Month 48	10.0 percentage of participants	4.8 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 3	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 6	20.0 percentage of participants	14.3 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 9	10.0 percentage of participants	9.5 percentage of participants	18.2 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 12	10.0 percentage of participants	9.5 percentage of participants	27.3 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 15	10.0 percentage of participants	19.0 percentage of participants	27.3 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 18	20.0 percentage of participants	23.8 percentage of participants	27.3 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 21	20.0 percentage of participants	9.5 percentage of participants	36.4 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 24	10.0 percentage of participants	19.0 percentage of participants	36.4 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 27	20.0 percentage of participants	19.0 percentage of participants	36.4 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 30	20.0 percentage of participants	14.3 percentage of participants	36.4 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 33	0.0 percentage of participants	14.3 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 36	10.0 percentage of participants	19.0 percentage of participants	27.3 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 39	20.0 percentage of participants	4.8 percentage of participants	18.2 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 42	10.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 45	10.0 percentage of participants	4.8 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4 - Month 48	10.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 3	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 6	20.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 9	0.0 percentage of participants	4.8 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 12	0.0 percentage of participants	4.8 percentage of participants	18.2 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 15	10.0 percentage of participants	4.8 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 18	10.0 percentage of participants	9.5 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 21	10.0 percentage of participants	9.5 percentage of participants	27.3 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 24	10.0 percentage of participants	4.8 percentage of participants	18.2 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 27	10.0 percentage of participants	14.3 percentage of participants	18.2 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 30	10.0 percentage of participants	4.8 percentage of participants	27.3 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 33	0.0 percentage of participants	4.8 percentage of participants	0.0 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 36	10.0 percentage of participants	9.5 percentage of participants	18.2 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 39	10.0 percentage of participants	4.8 percentage of participants	18.2 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 42	10.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 45	10.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants
Percentage of Participants With Molecular Response (MR) MR4.5 - Month 48	0.0 percentage of participants	0.0 percentage of participants	9.1 percentage of participants

SECONDARY outcome

Timeframe: Month 3

Population: Safety Population includes all participants who have received at least 1 dose of study drug, with data available for analysis.

MR1 was defined as the percentage of participants achieving a ratio of ≤10% BCR ABL to ABL transcripts on the international scale at 3 months.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=21 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=11 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Percentage of Participants With MR1	70.0 percentage of participants	66.7 percentage of participants	63.6 percentage of participants

SECONDARY outcome

Timeframe: From first dose up to 30 days post last dose (Up to approximately 46 months)

Population: Safety Population includes all participants who have received at least 1 dose of study drug.

TE-AOE: arterial occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. TE-VTE: vascular occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. AE: any untoward medical occurrence in participant administered pharmaceutical product; untoward medical occurrence does not necessarily have causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is congenital anomaly/birth defect/is medically important event.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=21 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=12 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) TE-AOE	0 percentage of participants	4.8 percentage of participants	8.3 percentage of participants
Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) TE-VOEs	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) AEs	100 percentage of participants	95.2 percentage of participants	100 percentage of participants
Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) SAEs	40.0 percentage of participants	14.3 percentage of participants	16.7 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 60 months

Population: Safety Population includes all participants who have received at least 1 dose of study drug. Only responders were analyzed for this outcome measure.

Time to MMR defined as the interval between the randomization date and the first date at which the criteria for response was met. MMR was defined as \<=0.1% BCR-ABL.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=5 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=9 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=5 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Time to Response	3.07 months Interval 3.0 to The upper limit of confidence interval (CI) was not estimable due to less number of participants with event.	6.29 months Interval 3.0 to 18.1	6.07 months Interval 3.0 to The upper limit of CI was not estimable due to less number of participants with event.

SECONDARY outcome

Timeframe: Up to approximately 60 months

Population: Safety Population includes all participants who have received at least 1 dose of study drug. Only responders were analyzed for this outcome measure.

Duration of response defined as the interval between the first assessment at which the criteria for response was met until the earliest date at which loss of response occurs, or the criteria for progression was met.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=5 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=9 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=5 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Duration of Response	NA months The median, lower limit and upper limit of CI were not estimable due to less number of participants with event.	NA months Interval 3.0 to The median and upper limit of CI were not estimable due to less number of participants with event.	NA months The median, lower limit and upper limit of CI were not estimable due to less number of participants with event.

SECONDARY outcome

Timeframe: Up to end of study (approximately 60 months)

Population: Safety Population includes all participants who have received at least 1 dose of study drug.

Progression-free survival (PFS) defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression was met (progression to AP- or BP CML), or death due to any cause, censored at the last response assessment.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=21 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=12 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Progression-free Survival (PFS)	NA months Interval 8.0 to The median and upper limit of CI were not estimable due to less number of participants with event.	NA months The median, lower limit and upper limit of CI were not estimable due to less number of participants with event.	NA months The median, lower limit and upper limit of CI were not estimable due to less number of participants with event.

SECONDARY outcome

Timeframe: Up to end of study (approximately 60 months)

Population: Safety Population includes all participants who have received at least 1 dose of study drug.

Overall survival (OS) defined as the interval between the first dose date of study treatment and date of death due to any cause, censored at the last contact date to be alive.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=21 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=12 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Overall Survival	NA months Interval 18.5 to The median and upper limit of CI were not estimable due to less number of participants with event.	NA months The median, lower limit and upper limit of CI were not estimable due to less number of participants with event.	NA months The median, lower limit and upper limit of CI were not estimable due to less number of participants with event.

SECONDARY outcome

Timeframe: 3 months after the first dose of study treatment

Population: Safety Population includes all participants who have received at least 1 dose of study drug.

CHR rate is defined as the percentage of participants achieving CHR at any time after initiation of study treatment. CHR is defined as achieving all of the following measurements: White blood cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets \<450 x 10\^9/L; No blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; Basophils in peripheral blood \<5%; No extramedullary involvement (including no hepatomegaly or splenomegaly).

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=21 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=12 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR)	60.0 percentage of participants Interval 26.2 to 87.8	81.0 percentage of participants Interval 58.1 to 94.6	50.0 percentage of participants Interval 21.1 to 78.9

SECONDARY outcome

Timeframe: From first dose up to end of treatment (Up to approximately 45 months)

Population: Safety Population includes all participants who have received at least 1 dose of study drug.

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

Outcome measures

Outcome measures
Measure	Cohort A: Ponatinib 30 mg n=10 Participants Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=21 Participants Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=12 Participants Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption TEAEs Leading to Treatment Discontinuation	10.0 percentage of participants	23.8 percentage of participants	25.0 percentage of participants
Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption TEAEs Leading to Dose Reduction	40.0 percentage of participants	19.0 percentage of participants	33.3 percentage of participants
Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption TEAEs Leading to Dose Interruption	70.0 percentage of participants	38.1 percentage of participants	41.7 percentage of participants

SECONDARY outcome

Timeframe: Up to end of study (Up to approximately 60 months)

Population: As the study was terminated, data was not collected and analyzed for this outcome measure.

Progression to AP is defined as: \>=15% and \<30% blasts in peripheral blood or bone marrow or \>=20% basophils in peripheral blood or bone marrow or \>=30% blasts + promyelocytes in peripheral blood or bone marrow (but \<30% blasts) or \<100\*10\^9 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP-CML is defined as: \>=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.

Outcome measures

Outcome data not reported

Adverse Events

Cohort A: Ponatinib 30 mg

Serious events: 4 serious events

Other events: 10 other events

Deaths: 1 deaths

Cohort B: Ponatinib 15 mg

Serious events: 3 serious events

Other events: 20 other events

Deaths: 1 deaths

Cohort C: Nilotinib 400 mg

Serious events: 2 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort A: Ponatinib 30 mg n=10 participants at risk Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.	Cohort B: Ponatinib 15 mg n=21 participants at risk Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.	Cohort C: Nilotinib 400 mg n=12 participants at risk Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
Infections and infestations Pneumonia	20.0% 2/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Infections and infestations Sepsis	0.00% 0/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	4.8% 1/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Infections and infestations Septic shock	0.00% 0/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	4.8% 1/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Investigations Platelet count decreased	20.0% 2/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	4.8% 1/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Blood and lymphatic system disorders Neutropenia	0.00% 0/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	8.3% 1/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Cardiac disorders Atrial flutter	0.00% 0/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	4.8% 1/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	4.8% 1/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	8.3% 1/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Injury, poisoning and procedural complications Femoral neck fracture	10.0% 1/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	4.8% 1/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	0.00% 0/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	4.8% 1/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/10 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	4.8% 1/21 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.	0.00% 0/12 • All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.

Other adverse events

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER