Trial Outcomes & Findings for Study Assessed the Safety and Efficacy of Eltrombopag in Chinese Refractory or Relapsed Severe Aplastic Anemia (SAA) Subjects. (NCT NCT03988608)

Last Updated: 2025-12-30

Results Overview

Hematologic response rate: percentage of subjects who met any of the International Working Group criteria: Platelet count: If platelet transfusion independent at baseline (BL): Transfusion independent and increase from BL by 20×10\^9/L or more; If platelet transfusion dependent at BL: No platelet transfusion requirement for 8 weeks; Hemoglobin: If red blood cells (RBC) transfusion independent at BL: transfusion independent and increase from BL by 15 g/L or more; If RBC transfusion dependent at BL: A decrease of at least 4 units in RBC transfusions in the post-treatment 8-week period (1 unit = RBC derived from 200 mL blood) or no RBC transfusion requirement for 8 weeks; Neutrophil count: In the absence of granulocyte colony stimulating factor (G-CSF) taken within 21 days preceding the blood sample collection: Increase from BL by 0.5×10\^9/L or more, or (if \< 0.5×10\^9/L at BL) increase by 100% or more. Patients who discontinued from the trial before week 26 were treated as non-responders.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

6 months (Week 26)

Results posted on

2025-12-30

Participant Flow

The study enrolled all 20 participants from 5 sites in China.

One of the main criteria for enrollment was for Chinese patients aged ≥ 18 years, previously diagnosed with SAA and who had insufficient response following at least one treatment course in the period time of \> 6 months of immunosuppression with a regimen containing anti-thymocyte globulin (ATG), anti-lymphocyte Immunoglobulin (ALG), and/or cyclophosphamide, or alemtuzumab.

Participant milestones

Participant milestones
Measure	Eltrombopag Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Overall Study STARTED	20
Overall Study Completed 26-week Treatment Phase	17
Overall Study Entered Week 52 Treatment Phase	15
Overall Study Completed Week 52 Treatment Phase	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Eltrombopag Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Overall Study Adverse Event	1
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	3
Overall Study Death	1

Baseline Characteristics

Study Assessed the Safety and Efficacy of Eltrombopag in Chinese Refractory or Relapsed Severe Aplastic Anemia (SAA) Subjects.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eltrombopag n=20 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Age, Continuous	39.0 years STANDARD_DEVIATION 13.25 • n=174 Participants
Sex: Female, Male Female	5 Participants n=174 Participants
Sex: Female, Male Male	15 Participants n=174 Participants
Race/Ethnicity, Customized Asian	20 Participants n=174 Participants

PRIMARY outcome

Timeframe: 6 months (Week 26)

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment. The patients who discontinued from the trial before Week 26 were treated as non-responders.

Outcome measures

Outcome measures
Measure	Eltrombopag n=20 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Hematologic Response Rate at 6 Months (Week 26) by Investigator	70.0 Percentage of participants Interval 49.2 to 86.0

SECONDARY outcome

Timeframe: Week (Wk) 13, Week 52

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment.

Hematologic response rate: percentage of subjects who met any of the International Working Group criteria: Platelet count: If platelet transfusion independent at baseline (BL): Transfusion independent and increase from BL by 20×10\^9/L or more; If platelet transfusion dependent at BL: No platelet transfusion requirement for 8 wks; Hemoglobin: If red blood cells (RBC) transfusion independent at BL: transfusion independent and increase from BL by 15 g/L or more; If RBC transfusion dependent at BL: A decrease of at least 4 units in RBC transfusions in the post-treatment 8-week period (1 unit =RBC derived from 200 mL blood) or no RBC transfusion requirement for 8 wks; Neutrophil count: In the absence of granulocyte colony stimulating factor (G-CSF) taken within 21 days preceding the blood sample collection: Increase from BL by 0.5×10\^9/L or more, or (if \< 0.5×10\^9/L at BL) increase by 100% or more. Patients who discontinued from the trial before wks 13 \& 26 were treated as non-responders.

Outcome measures

Outcome measures
Measure	Eltrombopag n=20 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Hematologic Response Rate by Investigator Week 13	65.0 Percentage of participants Interval 44.2 to 82.3
Hematologic Response Rate by Investigator Week 52	65.0 Percentage of participants Interval 44.2 to 82.3

SECONDARY outcome

Timeframe: Baseline, Week 13, Week 26, Week 52

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment. These were the patients in FAS with a valid assessment for the outcome measure at baseline and at Weeks 13, 26 and 52.

Change (increase from baseline) in platelet count (in the absence of platelet transfusion) were calculated according to the lab test results entered into the case report form (CRF) that were summarized at each visit using descriptive statistics. Platelet Count (×109/L) was assessed in hematology test.

Outcome measures

Outcome measures
Measure	Eltrombopag n=20 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Change From Baseline in Platelet Count Baseline (BL)	10.725 10^9 platelets/liter Standard Deviation 7.8731
Change From Baseline in Platelet Count Change from BL at Week 13/Day92	10.265 10^9 platelets/liter Standard Deviation 14.1456
Change From Baseline in Platelet Count Change from BL at Week 26/Day 183	26.933 10^9 platelets/liter Standard Deviation 30.5304
Change From Baseline in Platelet Count Change from BL at Week 52/Day 365	41.071 10^9 platelets/liter Standard Deviation 56.6816

SECONDARY outcome

Timeframe: Baseline, Week 13, Week 26 and Week 52

Change (increase from baseline) in hemoglobin (in the absence of red blood cell (RBC) transfusion) were calculated according to the lab test results entered into the CRF that were summarized at each visit using descriptive statistics. Hemoglobin level (g/L) was assessed in hematology test.

Outcome measures

Outcome measures
Measure	Eltrombopag n=20 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Change From Baseline in Hemoglobin Levels Baseline	66.9 gram/liter Standard Deviation 19.90
Change From Baseline in Hemoglobin Levels Change from BL at Week 13/Day92	22.4 gram/liter Standard Deviation 23.47
Change From Baseline in Hemoglobin Levels Change from baseline at Week 26/Day 183	31.9 gram/liter Standard Deviation 29.20
Change From Baseline in Hemoglobin Levels Change from BL at Week 52/Day 365	32.9 gram/liter Standard Deviation 33.21

SECONDARY outcome

Timeframe: Baseline, Week 13, Week 26 and Week 52

Change (increase from baseline) in neutrophil count (in the absence of granulocyte colony stimulating factor (G-CSF) and calculated according to the lab test results entered into the CRF that were summarized at each visit using descriptive statistics). Neutrophil count (×109/L) was assessed in hematology test.

Outcome measures

Outcome measures
Measure	Eltrombopag n=20 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Change From Baseline in Neutrophil Count Baseline	1.199 10^9 neutrophils/liter Standard Deviation 1.3483
Change From Baseline in Neutrophil Count Change from BL at Week 13/Day 92 (n = 16)	-0.160 10^9 neutrophils/liter Standard Deviation 1.4141
Change From Baseline in Neutrophil Count Change from baseline at Week 26/Day 183 (n = 14)	0.196 10^9 neutrophils/liter Standard Deviation 1.6822
Change From Baseline in Neutrophil Count Change from BL at Week 52/Day 365 (n = 14)	0.447 10^9 neutrophils/liter Standard Deviation 1.5764

SECONDARY outcome

Timeframe: Baseline to Week 26

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment and achieved a hematologic response.

Time to hematological response was defined as the time from the date of first study drug administration to the first hematological response. If a participant did not meet hematological response before or at the cutoff date, censoring was performed using the date of last assessment.

Outcome measures

Outcome measures
Measure	Eltrombopag n=20 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Time to Hematologic Response by Investigator	10.0 Weeks Interval 8.0 to 12.0

SECONDARY outcome

Timeframe: up to approx. 3.5 years

Population: Participants in the FAS who achieved a hematologic response. The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned and received one dose of study treatment and achieved a hematologic response.

Duration of hematologic response (any response according to the response criteria for the primary endpoint). For subjects who responded, duration of response was defined as the number of weeks from the first date of hematological response until the first date of relapse or death. Only participants with at least two response assessments were included for the duration of hematologic response assessment.

Outcome measures

Outcome measures
Measure	Eltrombopag n=15 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Duration of Hematologic Response by Investigator	NA Weeks Interval 22.3 to NA: Not estimable due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Baseline, Week 13, Week 26 and Week 52

Population: Participants in the FAS who were platelet transfusion dependent at baseline and who did not discontinue prior to the corresponding visit date (Week 13, 26 and 52).

For subjects receiving transfusion (platelets) at baseline, the frequency of platelet transfusion in each period (Baseline: 4 weeks before Day 1; Week 13, 26, 52: 4 weeks before each visit day) was summarized using descriptive statistics.

Outcome measures

Outcome measures
Measure	Eltrombopag n=10 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Frequency of Platelets Transfusion Week 52	0.0 occurrences Standard Deviation 0.00
Frequency of Platelets Transfusion Baseline	1.8 occurrences Standard Deviation 1.32
Frequency of Platelets Transfusion Week 13	0.4 occurrences Standard Deviation 0.88
Frequency of Platelets Transfusion Week 26	0.1 occurrences Standard Deviation 0.35

SECONDARY outcome

Timeframe: Baseline, Week 13, Week 26 and Week 52

Population: Participants in the FAS who were platelet transfusion dependent at baseline and who did not discontinue prior to the corresponding visit date (Week 13, 26 and 52).

The amount of transfusion was defined as the sum of transfusion multiplied by the volume of transfusion.

Outcome measures

Outcome measures
Measure	Eltrombopag n=10 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Amount of Platelets Transfusion Week 13	0.4 Units Standard Deviation 0.88
Amount of Platelets Transfusion Week 26	0.1 Units Standard Deviation 0.35
Amount of Platelets Transfusion Week 52	0.0 Units Standard Deviation 0.00
Amount of Platelets Transfusion Baseline	3.7 Units Standard Deviation 3.63

SECONDARY outcome

Timeframe: Baseline, Week 13, Week 26 and Week 52

Population: Participants in the FAS who were RBC transfusion dependent at baseline and who did not discontinue prior to the corresponding visit date (Week 13, 26 and 52).

For subjects receiving transfusion (RBC (Red Blood Cell)) at baseline, the frequency of RBC transfusion in each period (Baseline: 8 weeks before Day 1; Week 13, 26, 52: 8 weeks before each visit day) was summarized using descriptive statistics.

Outcome measures

Outcome measures
Measure	Eltrombopag n=14 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Frequency of Red Blood Cells (RBC) Transfusion Baseline	3.0 occurrences Standard Deviation 2.04
Frequency of Red Blood Cells (RBC) Transfusion Week 13	1.8 occurrences Standard Deviation 2.83
Frequency of Red Blood Cells (RBC) Transfusion Week 26	1.5 occurrences Standard Deviation 2.02
Frequency of Red Blood Cells (RBC) Transfusion Week 52	0.5 occurrences Standard Deviation 0.71

SECONDARY outcome

Timeframe: Baseline, Week 13, Week 26 and Week 52

Population: Participants in the FAS who were RBC transfusion dependent at baseline and who did not discontinue prior to the corresponding visit date (Week 13, 26 and 52).

The amount of RBC transfusion was defined as the sum of transfusion multiplied by the volume of transfusion.

Outcome measures

Outcome measures
Measure	Eltrombopag n=14 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Amount of Red Blood Cells (RBC) Transfusion Baseline	6.6 Units Standard Deviation 4.16
Amount of Red Blood Cells (RBC) Transfusion Week 13	3.8 Units Standard Deviation 6.18
Amount of Red Blood Cells (RBC) Transfusion Week 25	3.0 Units Standard Deviation 4.02
Amount of Red Blood Cells (RBC) Transfusion Week 52	1.4 Units Standard Deviation 1.90

SECONDARY outcome

Timeframe: pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14

Population: Participants in the pharmacokinetic analysis set (PAS) who had an evaluable pharmacokinetic (PK) profile at steady state. The pharmacokinetic analysis set (PAS) included all patients who received at least one dose of eltrombopag and who had at least one evaluable PK sample.

Cmax is the maximum (peak) observed plasma drug concentration after single dose administration (mass\*volume-1). Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state.

Outcome measures

Outcome measures
Measure	Eltrombopag n=12 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Plasma PK Parameters of Eltrombopag: Cmax	3450 ng/mL Standard Deviation 1900

SECONDARY outcome

Timeframe: pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14

Tmax is the time to reach maximum (peak) plasma drug concentration after single dose administration (time). Blood samples were collected from all patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state.

Outcome measures

Outcome measures
Measure	Eltrombopag n=12 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Plasma PK Parameters of Eltrombopag: Tmax	3.73 hour Interval 0.917 to 5.9

SECONDARY outcome

Timeframe: pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14

AUCtau is the area under the curve calculated to the end of a dosing interval (tau) at steady-state (amount\*time\*volume-1). AUClast is the AUC calculated from time 0 to the time of the last quantifiable concentration. Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state.

Outcome measures

Outcome measures
Measure	Eltrombopag n=12 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Plasma PK Parameters of Eltrombopag: AUCtau & AUClast AUCtau	67900 h*ng/mL Standard Deviation 31400
Plasma PK Parameters of Eltrombopag: AUCtau & AUClast AUClast	62700 h*ng/mL Standard Deviation 33200

SECONDARY outcome

Timeframe: pre-dose, and 1, 2, 4, 6, 8 and 24 hours post-dose on Day 14

Population: Participants in the pharmacokinetic analysis set (PAS) who had an evaluable PK profile at steady state and who had a valid value for the outcome measure. The PAS included all patients who received at least one dose of eltrombopag and who had at least one evaluable PK sample.

Steady State (CLss/F) is the apparent systemic (or total body) clearance at steady state from plasma (volume/time) following drug administration. Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state.

Outcome measures

Outcome measures
Measure	Eltrombopag n=11 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Plasma PK Parameters of Eltrombopag: CLss/F	0.441 L/h Standard Deviation 0.178

SECONDARY outcome

Timeframe: Pre-dose sample on the 15th day after each new dose level was started

Population: The pharmacokinetic analysis set (PAS) included all patients who received at least one dose of eltrombopag and who had at least one evaluable PK sample.

Ctrough is the pre-dose concentration at the end of dose interval (mass\*volume-1). Blood samples were collected from patients to assess the plasma concentrations of eltrombopag. The plasma concentrations were used to determine the PK characteristics of eltrombopag. Serial intensive PK blood samples were collected for the initial 25 mg/day dose to provide at least 12 participants with evaluable PK profiles at steady state. Sparse PK blood samples were collected for the other doses and in the rest of the patients for Ctrough assessment.

Outcome measures

Outcome measures
Measure	Eltrombopag n=20 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Plasma Trough Concentration of Eltrombopag concentration at 25 mg	2180 ng/mL Standard Deviation 1490
Plasma Trough Concentration of Eltrombopag concentration at 50 mg	5180 ng/mL Standard Deviation 3320
Plasma Trough Concentration of Eltrombopag concentration at 75 mg	11300 ng/mL Standard Deviation 6000
Plasma Trough Concentration of Eltrombopag concentration at 100 mg	14700 ng/mL Standard Deviation 8070
Plasma Trough Concentration of Eltrombopag concentration at 125 mg	20300 ng/mL Standard Deviation 11300
Plasma Trough Concentration of Eltrombopag concentration at 150 mg	23800 ng/mL Standard Deviation 13700

SECONDARY outcome

Timeframe: From Baseline up to approx. 2.9 years

Population: The Full Analysis Set (FAS) comprised all patients to whom study treatment had been assigned.

Number of participants with clonal evolution with a normal karyotype at baseline including clonal evolution to PNH (Paroxysmal Nocturnal Hemoglobinuria), evolution to AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndromes).

Outcome measures

Outcome measures
Measure	Eltrombopag n=20 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
Number of Participants With Clonal Evolution	2 Participants

POST_HOC outcome

Timeframe: On-treatment deaths: up to approx. 3.5 years, post-treatment deaths: up to approx. 3.5 years

Population: All enrolled participants.

Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period.

Outcome measures

Outcome measures
Measure	Eltrombopag n=20 Participants Participants started eltrombopag treatment at 25 mg/day from Day 1 and increased by 25 mg/day every 2 weeks according to the platelet count up to 150 mg/day.
All Collected Deaths All Deaths	1 Participants
All Collected Deaths On-treatment deaths	0 Participants
All Collected Deaths Post-treatment deaths	1 Participants

Adverse Events

Eltrombopag (On-treatment)

Serious events: 8 serious events

Other events: 19 other events

Deaths: 0 deaths

Eltrombopag (Post-treatment)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Eltrombopag (On-treatment) n=20 participants at risk Safety data collected from first dose of study medication up to 30 days after last dose.	Eltrombopag (Post-treatment) Deaths collected from 31 days after last dose of study medication up to end of study. These are not considered adverse events.
Blood and lymphatic system disorders Febrile neutropenia	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Gastrointestinal disorders Gastritis	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Gastrointestinal disorders Gastrointestinal haemorrhage	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
General disorders Pyrexia	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Hepatobiliary disorders Liver injury	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Infections and infestations Pneumonia	15.0% 3/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Infections and infestations Spermatic cord funiculitis	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Infections and infestations Upper respiratory tract infection	10.0% 2/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Injury, poisoning and procedural complications Intentional product misuse	10.0% 2/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Musculoskeletal and connective tissue disorders Groin pain	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Musculoskeletal and connective tissue disorders Osteonecrosis	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Nervous system disorders Syncope	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Reproductive system and breast disorders Abnormal uterine bleeding	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.0% 1/20 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.	— 0/0 • Deaths were collected from the first dose until end of study, a maximum duration of up to 3.5 years. On-treatment deaths were collected within 30 days of the last dose, while post-treatment deaths were collected more than 30 days after the last dose for those who discontinued treatment early. Adverse events were collected from the first dose until 30 days after the last dose, also up to a maximum duration if 3.5 years. Adverse Events were not collected in the post-treatment period. Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events.

Other adverse events

Additional Information

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