Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Ixazomib in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma Initially Treated With an Injection of Proteasome Inhibitor-Based Therapy (NCT NCT03416374)

Results Overview

PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase \>10 mg/dl or bone marrow plasma cell ≥10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

45 participants

Primary outcome timeframe

Up to 12 months

Results posted on

2022-09-27

Participant Flow

Participant s took part in the survey at 33 investigative sites in Japan, from 18 February 2018 to 28 May 2021.

A total of 45 participants were enrolled and received the study treatment in this study.

Participant milestones

Participant milestones
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Treatment Period I STARTED	6	39
Treatment Period I COMPLETED	0	0
Treatment Period I NOT COMPLETED	6	39
Between Treatment Period I and II STARTED	6	39
Between Treatment Period I and II COMPLETED	6	30
Between Treatment Period I and II NOT COMPLETED	0	9
Treatment Period II STARTED	6	30
Treatment Period II COMPLETED	2	12
Treatment Period II NOT COMPLETED	4	18

Reasons for withdrawal

Reasons for withdrawal
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Between Treatment Period I and II Other	0	9
Treatment Period II Lack of Efficacy	3	11
Treatment Period II Adverse Event	1	4
Treatment Period II Death	0	1
Treatment Period II Other	0	2

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	Total n=45 Participants Total of all reporting groups
Age, Continuous	71.8 Years STANDARD_DEVIATION 8.57 • n=6 Participants	70.5 Years STANDARD_DEVIATION 9.40 • n=39 Participants	70.7 Years STANDARD_DEVIATION 9.21 • n=45 Participants
Sex: Female, Male Female	5 Participants n=6 Participants	16 Participants n=39 Participants	21 Participants n=45 Participants
Sex: Female, Male Male	1 Participants n=6 Participants	23 Participants n=39 Participants	24 Participants n=45 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Japan	6 Participants n=6 Participants	39 Participants n=39 Participants	45 Participants n=45 Participants
Height	153.0 Centimeters (cm) STANDARD_DEVIATION 9.70 • n=6 Participants	158.5 Centimeters (cm) STANDARD_DEVIATION 8.29 • n=39 Participants	157.8 Centimeters (cm) STANDARD_DEVIATION 8.58 • n=45 Participants
Weight	52.85 Kilograms (kg) STANDARD_DEVIATION 7.204 • n=6 Participants • The number analyzed is the number of participants with data available for analysis.	57.87 Kilograms (kg) STANDARD_DEVIATION 10.380 • n=37 Participants • The number analyzed is the number of participants with data available for analysis.	57.17 Kilograms (kg) STANDARD_DEVIATION 10.081 • n=43 Participants • The number analyzed is the number of participants with data available for analysis.
BMI	22.60 Kilogram (kg)/meter (m)^2] STANDARD_DEVIATION 2.619 • n=6 Participants • The number analyzed is the number of participants with data available for analysis.	22.91 Kilogram (kg)/meter (m)^2] STANDARD_DEVIATION 2.512 • n=37 Participants • The number analyzed is the number of participants with data available for analysis.	22.86 Kilogram (kg)/meter (m)^2] STANDARD_DEVIATION 2.497 • n=43 Participants • The number analyzed is the number of participants with data available for analysis.
Body Surface Area	1.487 m^2 STANDARD_DEVIATION 0.1395 • n=6 Participants • The number analyzed is the number of participants with data available for analysis.	1.583 m^2 STANDARD_DEVIATION 0.1760 • n=37 Participants • The number analyzed is the number of participants with data available for analysis.	1.569 m^2 STANDARD_DEVIATION 0.1732 • n=43 Participants • The number analyzed is the number of participants with data available for analysis.
International Staging System (at Initial Diagnosis) Stage I	2 Participants n=6 Participants	17 Participants n=39 Participants	19 Participants n=45 Participants
International Staging System (at Initial Diagnosis) Stage II	3 Participants n=6 Participants	14 Participants n=39 Participants	17 Participants n=45 Participants
International Staging System (at Initial Diagnosis) Stage III	1 Participants n=6 Participants	8 Participants n=39 Participants	9 Participants n=45 Participants
International Staging System (at First Treatment [Period I]) Stage I	5 Participants n=6 Participants	19 Participants n=39 Participants	24 Participants n=45 Participants
International Staging System (at First Treatment [Period I]) Stage II	1 Participants n=6 Participants	12 Participants n=39 Participants	13 Participants n=45 Participants
International Staging System (at First Treatment [Period I]) Stage III	0 Participants n=6 Participants	5 Participants n=39 Participants	5 Participants n=45 Participants
International Staging System (at First Treatment [Period I]) Missing	0 Participants n=6 Participants	3 Participants n=39 Participants	3 Participants n=45 Participants
Eastern Cooperative Oncology Group performance status (ECOG P.S.) Scale = 0	4 Participants n=6 Participants	29 Participants n=39 Participants	33 Participants n=45 Participants
Eastern Cooperative Oncology Group performance status (ECOG P.S.) Scale = 1	2 Participants n=6 Participants	8 Participants n=39 Participants	10 Participants n=45 Participants
Eastern Cooperative Oncology Group performance status (ECOG P.S.) Scale = 2	0 Participants n=6 Participants	2 Participants n=39 Participants	2 Participants n=45 Participants
Eastern Cooperative Oncology Group performance status (ECOG P.S.) Scale = 3	0 Participants n=6 Participants	0 Participants n=39 Participants	0 Participants n=45 Participants
Eastern Cooperative Oncology Group performance status (ECOG P.S.) Scale = 4	0 Participants n=6 Participants	0 Participants n=39 Participants	0 Participants n=45 Participants

PRIMARY outcome

Timeframe: Up to 12 months

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

PFS rate was defined as the percentage of participants who were alive and have not had disease progression at 12 months after the date of first dose of treatment in Treatment Period I. PFS was assessed by International Myeloma Working Group (IMWG) Criteria (2014 version). Per IMWG criteria, progressive disease (PD): serum M-component increase ≥0.5 g/dl or urine M-component increase ≥200 mg/24-hour/ difference between involved and uninvolved free light chain (FLC) levels increase \>10 mg/dl or bone marrow plasma cell ≥10%/ development of new/ increase in size of existing bone lesions or soft tissue plasmacytoma or development of hypercalcemia.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Progression-Free Survival (PFS) Rate at 12 Months From the Start of Study Treatment	50.0 Percentage of Participants Interval 15.3 to 84.7	48.7 Percentage of Participants Interval 34.7 to 62.9	48.9 Percentage of Participants Interval 35.9 to 62.0

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period

OS was defined as the period from the first dose of treatment in Treatment Period I to the time when death (regardless of the cause of death) was confirmed. Participants who were still alive were censored at the last confirmed date of survival or the date of data cut-off, whichever was earlier.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Overall Survival (OS) From the Start of Study Treatment	NA Months Interval 16.0 to NA: Data not available due to below the level of detection and insufficient number of participants with events. OS data were not mature, and the median OS was not reached.	NA Months NA: Data not available due to below the level of detection and insufficient number of participants with events. OS data were not mature, and the median OS was not reached.	NA Months NA: Data not available due to below the level of detection and insufficient number of participants with events. OS data were not mature, and the median OS was not reached.

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

PFS was defined as the period from the first dose of treatment in Treatment Period I to the time of confirmed PD or confirmed death (regardless of the cause of death), whichever is earlier. PFS was assessed by IMWG Criteria.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
PFS From the Start of Study Treatment	NA Months Interval 4.86 to NA: data not available due to below the level of detection and insufficient number of participants with events. PFS data were not mature, and the median PFS was not reached.	28.96 Months Interval 21.32 to NA: data not available due to below the level of detection and insufficient number of participants with events. PFS data were not mature, and the median PFS was not reached.	28.96 Months Interval 21.32 to NA: data not available due to below the level of detection and insufficient number of participants with events. PFS data were not mature, and the median PFS was not reached.

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

VGPR or better (CR + VGPR) were assessed by IMWG Criteria. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to \<200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Percentage of Participants Who Achieved VGPR or Better (CR + VGPR)	33.3 Percentage of Participants Interval 4.3 to 77.7	43.6 Percentage of Participants Interval 27.8 to 60.4	42.2 Percentage of Participants Interval 27.7 to 57.8

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

MRD was measured by the flow cytometry method using bone marrow aspiration. Reported data were numbers of participants with MRD positive and negative in bone marrow in participants who achieved CR. MRD positive was categorized into three sensitivity levels with the numbers of cells counted (10\^-4 to - Max; 10\^-5 to 10\^-4; 10\^-6 to 10\^-5). MRD negativity is defined as absence of MRD and MRD positivity is defined as presence of MRD. If a participant is MRD-positive at their first evaluation and MRD-negative after re-examination, the participant will be considered to be MRD-negative. CR will be assessed by IMWG Criteria.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=2 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=9 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=11 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR Sensitivity Level; 10^-4=< - Max	0 Participants	1 Participants	1 Participants
Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR Sensitivity Level; 10^-5=< - <10^-4	1 Participants	2 Participants	3 Participants
Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR Sensitivity Level; 10^-6=< - <10^-5	1 Participants	1 Participants	2 Participants
Number of Participants With Minimal Residual Disease (MRD) Positive or Negative in Bone Marrow in Participants Who Achieved CR Negative	0 Participants	5 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Best response is defined as the cumulative numbers of participants who achieve each level of best response including PR, VGPR and CR assessed with IMWG Criteria, after each cycle of treatment. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to \<200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Percentage of Participants Who Achieve or Maintain Any Best Response CR	33.3 Percentage of Participants	23.1 Percentage of Participants	24.4 Percentage of Participants
Percentage of Participants Who Achieve or Maintain Any Best Response VGPR	0 Percentage of Participants	20.5 Percentage of Participants	17.8 Percentage of Participants
Percentage of Participants Who Achieve or Maintain Any Best Response PR	50.0 Percentage of Participants	28.2 Percentage of Participants	31.1 Percentage of Participants

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

ORR is defined as the percentage of participants who achieve a best response of PR or better including stringent complete response (sCR), VGPR and PR assessed with IMWG Criteria, after the start of the study treatment. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to \<200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Overall Response Rate (ORR)	83.3 Percentage of Participants Interval 35.9 to 99.6	71.8 Percentage of Participants Interval 55.1 to 85.0	73.3 Percentage of Participants Interval 58.1 to 85.4

SECONDARY outcome

Timeframe: 12 months

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Percentage of Participants Continuing Treatment With Ixazomib at 12 Months From the Start of Study Treatment	50.0 Percentage of Participants Interval 11.8 to 88.2	35.9 Percentage of Participants Interval 21.2 to 52.8	37.8 Percentage of Participants Interval 23.8 to 53.5

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

DOR is defined as the time from the date of first documentation of response ≥PR to the date of first documentation of PD or death due to any cause. PR and PD will be assessed with IMWG Criteria. Per IMWG criteria, PR (partial response): ≥50% reduction of serum M protein+reduction in 24-hour urinary M protein by ≥90%/ to \<200 mg/24-hour or ≥50% decrease in difference between involved and uninvolved free light chain (FLC) levels/ ≥50% reduction in bone marrow plasma cells, if ≥30% at baseline/ ≥50% reduction in size of soft tissue plasmacytomas. VGPR (very good PR): serum+urine M-protein detectable by immunofixation but not on electrophoresis/ ≥90% reduction in serum M-protein+urine Mprotein level \<100 mg/24-hour. CR (complete response): negative immunofixation on serum+urine+disappearance of soft tissue plasmacytomas+\<5% plasma cells in bone marrow.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=5 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=28 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=33 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Duration of Response (DOR)	15.31 Months Interval 3.64 to NA: data not available due to below the level of detection and insufficient number of participants with events. DOR data were not mature.	28.03 Months Interval 20.4 to NA: data not available due to below the level of detection and insufficient number of participants with events. DOR data were not mature.	28.03 Months Interval 20.4 to NA: data not available due to below the level of detection and insufficient number of participants with events. DOR data were not mature.

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

TTNT is defined as the period from the start of study treatment Period I to the start of next line treatment.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Time to Next Treatment (TTNT)	21.59 Months Interval 4.99 to NA: Upper limit for 95% CI was not available due to below the level of detection and insufficient number of participants with events.	32.26 Months Interval 12.43 to 35.44	32.26 Months Interval 14.88 to 35.44

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

DOT is defined as the treatment duration of study drug at study treatment Period I.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Duration of Therapy (DOT)	14.69 Months Interval 4.86 to NA: Upper limit for 95% CI was not available due to below the level of detection and insufficient number of participants with events.	12.43 Months Interval 7.74 to 24.79	12.43 Months Interval 8.86 to 24.79

SECONDARY outcome

Timeframe: Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

EORTC QLQ-C30 contains 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial difficulties) and a global health status/QOL scale (Global Health Status). EORTC QLQ-C30 contains 28 questions (4-point scale where 1=Not at all \[best\] to 4=Very Much \[worst\]) and 2 questions (7-point scale where 1=Very poor \[worst\] to 7= Excellent \[best\]). Raw scores are converted into scale scores ranging from 0 to 100. For the functional scales and the global health status/QOL scale, higher scores represent better QOL; for the symptom scales, lower scores represent better QOL.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Baseline	44.44 Score on a Scale Standard Deviation 40.369	63.25 Score on a Scale Standard Deviation 24.085	60.74 Score on a Scale Standard Deviation 26.981
Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Cycle 23	0 Score on a Scale Standard Deviation NA NA: data not available due to below the level of detection and insufficient number of participants with events.	54.17 Score on a Scale Standard Deviation 8.740	46.43 Score on a Scale Standard Deviation 21.973
Patient-Reported Outcome Health-Related Quality of Life (HRQoL) Based on Global Health Status Scale of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Cycle 32	—	50.00 Score on a Scale Standard Deviation 23.750	50.00 Score on a Scale Standard Deviation 23.750

SECONDARY outcome

Timeframe: Baseline and End of Treatment (Up to 23 cycles for VRd Group, Up to 32 cycles for KRd and Overall Group, each cycle was of 28 days)

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

EORTC QLQ-MY20 has 20 items across 4 independent subscales, 2 functional subscales (body image, future perspective), and 2 symptoms scales (disease symptoms, and side effects of treatment). Scores are averaged, and transformed to 0-100 scale. For the functional scales, high scores represent improvement. For the symptom scales, higher scores represent worsening.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Disease Symptoms: Baseline	24.07 Score on a Scale Standard Deviation 21.564	19.23 Score on a Scale Standard Deviation 16.756	19.88 Score on a Scale Standard Deviation 17.266
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Disease Symptoms: Cycle 23	0 Score on a Scale Standard Deviation NA Number of participants analyzed was one.	4.63 Score on a Scale Standard Deviation 7.384	3.97 Score on a Scale Standard Deviation 6.964
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Disease Symptoms: Cycle 32	—	2.78 Score on a Scale Standard Deviation 3.928	2.78 Score on a Scale Standard Deviation 3.928
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Side-Effects of Treatment: Baseline	16.67 Score on a Scale Standard Deviation 12.776	16.60 Score on a Scale Standard Deviation 14.464	16.61 Score on a Scale Standard Deviation 14.115
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Side-Effects of Treatment: Cycle 23	3.70 Score on a Scale Standard Deviation NA Number of participants analyzed was one.	16.05 Score on a Scale Standard Deviation 3.825	14.29 Score on a Scale Standard Deviation 5.828
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Side-Effects of Treatment: Cycle 32	—	18.52 Score on a Scale Standard Deviation 15.713	18.52 Score on a Scale Standard Deviation 15.713
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Body Image: Baseline	44.44 Score on a Scale Standard Deviation 45.542	23.08 Score on a Scale Standard Deviation 26.660	25.93 Score on a Scale Standard Deviation 30.058
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Body Image: Cycle 23	0 Score on a Scale Standard Deviation NA Number of participants analyzed was one.	16.67 Score on a Scale Standard Deviation 18.257	14.29 Score on a Scale Standard Deviation 17.817
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Body Image: Cycle 32	—	16.67 Score on a Scale Standard Deviation 23.570	16.67 Score on a Scale Standard Deviation 23.570
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Future Perspective: Baseline	66.67 Score on a Scale Standard Deviation 37.185	44.16 Score on a Scale Standard Deviation 24.114	47.16 Score on a Scale Standard Deviation 26.817
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Future Perspective: Cycle 23	11.11 Score on a Scale Standard Deviation NA Number of participants analyzed was one.	35.19 Score on a Scale Standard Deviation 8.364	31.75 Score on a Scale Standard Deviation 11.878
Patient-Reported Outcome HRQoL Based on EORTC Multiple Myeloma Module (EORTC QLQ-MY20) Score Future Perspective: Cycle 32	—	27.78 Score on a Scale Standard Deviation 7.857	27.78 Score on a Scale Standard Deviation 7.857

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Modified QALYs was calculated from the score of EORTC QLQ-C30. The health-related quality of life scale score of EORTC QLQ-C30 was converted into a utility value ranging from 0 (dead) to 1 (perfect health), and used to adjust the value of survival years; this value was assessed as the modified QALY.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=4 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=16 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=20 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Evaluation of Modified Quality-Adjusted Life-Years (QALYs)	0.467 Quality-Adjusted Life-Years Interval 0.25 to 0.89	0.534 Quality-Adjusted Life-Years Interval 0.17 to 0.85	0.518 Quality-Adjusted Life-Years Interval 0.17 to 0.89

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Number of events with hospitalization per participants-month in Treatment Period I and Treatment Period II was reported.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Healthcare Resource Utilization (HCRU): Number of Events With Hospitalization Per Participants-Month	1.9 Number of Events per Participants-Month	2.9 Number of Events per Participants-Month	2.7 Number of Events per Participants-Month

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

HCRU was calculated from Exposure-adjusted rate of hospitalization events (per participants-months) and the duration of hospitalization among participants in Treatment Period I and Treatment Period II. Duration of hospital stay per participants in Treatment Period I and Treatment Period II was reported.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Healthcare Resource Utilization (HCRU): Duration of Hospital Stay Per Participants	14.8 Days Standard Deviation 16.01	19.4 Days Standard Deviation 18.14	18.8 Days Standard Deviation 17.77

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

RDI for each study drug is defined as 100\*(Total amount of dose taken)/(Total prescribed dose of treated cycles), where total prescribed dose equals \[dose prescribed at enrollment\* number of prescribed doses per cycle\* the number of treated cycles\].

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Relative Dose Intensity (RDI) Bortezomib, Ixazomib	71.93 Percent Interval 58.2 to 97.2	—	—
Relative Dose Intensity (RDI) Carfilzomib, Ixazomib	87.70 Percent Interval 27.0 to 108.4	—	—
Relative Dose Intensity (RDI) Bortezomib/Carfilzomib, Ixazomib	83.24 Percent Interval 27.0 to 108.4	—	—
Relative Dose Intensity (RDI) Lenalidomide	47.18 Percent Interval 9.0 to 100.4	—	—
Relative Dose Intensity (RDI) Dexamethasone	48.61 Percent Interval 6.6 to 105.3	—	—

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Full Analysis Set (FAS): all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

Outcome measures

Outcome measures
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Percentage of Participants With Bone Lesions (Bone Evaluation)	100.0 Percentage of Participants Interval 29.2 to 100.0	59.1 Percentage of Participants Interval 36.4 to 79.3	64.0 Percentage of Participants Interval 42.5 to 82.0

SECONDARY outcome

Timeframe: Up to 39 months as a maximum

Population: Safety Analysis Set: all participants who were enrolled in Treatment Period I and who receive at least one dose of any therapy during the Treatment Period.

An adverse event (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	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 Participants Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 Participants Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 Participants Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Number of Participants Reporting One or More Treatment-Emergent AEs (TEAEs)	6 Participants	35 Participants	41 Participants

Adverse Events

[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy

Serious events: 14 serious events

Other events: 31 other events

Deaths: 2 deaths

[Overall]; Combination Therapy + Ixazomib Therapy

Serious events: 17 serious events

Other events: 37 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	[VRd]; Bortezomib + Lenalidomide + Dexamethasone Therapy n=6 participants at risk Bortezomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[KRd]; Carfilzomib + Lenalidomide + Dexamethasone Therapy n=39 participants at risk Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)	[Overall]; Combination Therapy + Ixazomib Therapy n=45 participants at risk Bortezomib + Lenalidomide + Dexamethasone, or Carfilzomib + Lenalidomide + Dexamethasone, standard recommended dose according to the package insert of each drug (Treatment Period I), followed by Ixazomib (4.0 mg) on Days 1, 8 and 15, plus Lenalidomide (25 mg) on Days 1 to 21, and Dexamethasone (40 mg) on Days 1, 8, 15 and 22, of a 28-day cycle (Treatment Period II)
Blood and lymphatic system disorders Anaemia	16.7% 1/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	7.7% 3/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	8.9% 4/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
Gastrointestinal disorders Diarrhoea	50.0% 3/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	25.6% 10/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	28.9% 13/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
Gastrointestinal disorders Constipation	16.7% 1/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	7.7% 3/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	8.9% 4/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
General disorders Malaise	16.7% 1/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	7.7% 3/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	8.9% 4/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
General disorders Pyrexia	16.7% 1/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	7.7% 3/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	8.9% 4/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
Infections and infestations Nasopharyngitis	33.3% 2/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	5.1% 2/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	8.9% 4/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
Investigations White blood cell count decreased	33.3% 2/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	23.1% 9/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	24.4% 11/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
Investigations Platelet count decreased	16.7% 1/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	20.5% 8/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	20.0% 9/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
Investigations Neutrophil count decreased	16.7% 1/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	15.4% 6/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	15.6% 7/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
Metabolism and nutrition disorders Decreased appetite	50.0% 3/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	0.00% 0/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	6.7% 3/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
Nervous system disorders Taste disorder	33.3% 2/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	2.6% 1/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	6.7% 3/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.
Skin and subcutaneous tissue disorders Rash	66.7% 4/6 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	7.7% 3/39 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.	15.6% 7/45 • Up to 39 months as a maximum At each visit the investigator had to document any occurrence of adverse events (AEs) 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. In this study, only AEs in total duration of both Treatment Period I and II were planned to be collected on the study protocol and reported in this section. There were no plans to collect AEs for each Period.

Additional Information

Medical 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