Trial Outcomes & Findings for Long-term Study of Romiplostim in Thrombocytopenic Pediatric Patients With Immune Thrombocytopenia (ITP) (NCT NCT02279173)

Last Updated: 2022-06-23

Results Overview

Platelet response was defined as a platelet count of ≥ 50 x 10⁹/L with no rescue medication use for ITP in the past 4 weeks. Monthly platelet response was calculated based on the median platelet count during each month. For each participant, the percentage of time with platelet response during the first 6 months was calculated as the number of months a platelet response was observed divided by the total number of months response was assessed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

203 participants

Primary outcome timeframe

Week 2 to Month 6, platelet response was assessed every week.

Results posted on

2022-06-23

Participant Flow

Children with immune thrombocytopenic purpura (ITP) and platelet counts ≤ 30×10⁹/L or uncontrolled bleeding were enrolled from December 2014 to August 2016 at 66 centers in 16 countries worldwide, including Eastern Europe (44%), Western Europe (25%), and US/Canada (21%).

All participants were assigned to receive weekly romiplostim. A subset of participants enrolled under a protocol supplement in the European Union (EU), Switzerland, and Turkey were enrolled into the following 2 cohorts: * bone marrow biopsy and aspirate at baseline and year 1 * bone marrow biopsy and aspirate at baseline and year 2

Participant milestones

Participant milestones
Measure	Romiplostim Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.
Overall Study STARTED	203
Overall Study Received Treatment	203
Overall Study Enrolled Under Protocol Supplement	79
Overall Study COMPLETED	109
Overall Study NOT COMPLETED	94

Reasons for withdrawal

Reasons for withdrawal
Measure	Romiplostim Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.
Overall Study Protocol-specified Criteria	67
Overall Study Withdrawal by Subject	20
Overall Study Decision by Sponsor	4
Overall Study Lost to Follow-up	3

Baseline Characteristics

Participants with available data

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Romiplostim n=203 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.
Age, Continuous	10.0 years n=5 Participants
Age, Customized ≥ 1 to < 6 years	49 Participants n=5 Participants
Age, Customized ≥ 6 to < 12 years	81 Participants n=5 Participants
Age, Customized ≥ 12 to < 18 years	73 Participants n=5 Participants
Sex: Female, Male Female	103 Participants n=5 Participants
Sex: Female, Male Male	100 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian	12 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	11 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	1 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized Other, Not Specified	11 Participants n=5 Participants
Race/Ethnicity, Customized White	164 Participants n=5 Participants
Years Since ITP Diagnosis	1.75 years n=5 Participants • Participants with available data
Age at ITP Diagnosis	5.97 years n=5 Participants • Participants with available data
Splenectomy Done Yes	10 Participants n=5 Participants
Splenectomy Done No	193 Participants n=5 Participants
Platelet Count	14.00 10⁹ cells/L n=5 Participants • Participants with available data
Number of Prior ITP Treatments	2.0 prior ITP treatments n=5 Participants • Participants with available data

PRIMARY outcome

Timeframe: Week 2 to Month 6, platelet response was assessed every week.

Population: The efficacy analysis set included all enrolled participants who received at least 1 dose of romiplostim

Outcome measures

Outcome measures
Measure	Romiplostim n=203 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.	Cohort 2 Participants enrolled under the protocol supplement in the EU, Switzerland, or Turkey received weekly romiplostim for 3 years and had a bone marrow biopsy at baseline and year 2.
Percentage of Time With a Platelet Response During the First 6 Months of Treatment	50.00 percentage of time Interval 16.67 to 83.33	—

PRIMARY outcome

Timeframe: Year 1 (Cohort 1) and year 2 (Cohort 2)

Population: The bone marrow analysis set includes participants who received at least 1 dose of romiplostim, who were recruited within the protocol supplement for the EU, Switzerland and Turkey and who had at least 1 bone marrow biopsy during the study after initiation of study treatment. Participants with available core biopsy results are included.

The percentage of participants who developed collagen as evidenced by trichrome staining, defined as a Grade 4 on the modified Bauermeister grading scale: Grade 0: No reticulin fibers demonstrable Grade 1: Occasional fine individual fibers and foci of a fine fiber network Grade 2: Fine fiber network throughout most of the section; no coarse fibers Grade 3: Diffuse fiber network with scattered thick coarse fibers but no mature collagen (negative to trichrome staining) Grade 4: Diffuse, often course fiber network with areas of collagenization (positive trichrome staining)

Outcome measures

Outcome measures
Measure	Romiplostim n=27 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.	Cohort 2 n=36 Participants Participants enrolled under the protocol supplement in the EU, Switzerland, or Turkey received weekly romiplostim for 3 years and had a bone marrow biopsy at baseline and year 2.
Percentage of Participants Who Developed Collagen After Exposure to Romiplostim	0.0 percentage of participants Interval 0.0 to 12.8	0.0 percentage of participants Interval 0.0 to 9.7

PRIMARY outcome

Timeframe: Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)

The percentage of participants with an increased modified Bauermeister grade defined as an increase by ≥ 2 severity grades or an increase to grade 4 (i.e., grade 0 to 2-4, grade 1 to 3-4, grade 2 to 4, or grade 3 to 4 over baseline). The modified Bauermeister grading scale: Grade 0: No reticulin fibers demonstrable Grade 1: Occasional fine individual fibers and foci of a fine fiber network Grade 2: Fine fiber network throughout most of the section; no coarse fibers Grade 3: Diffuse fiber network with scattered thick coarse fibers but no mature collagen (negative to trichrome staining) Grade 4: Diffuse, often course fiber network with areas of collagenization (positive trichrome staining) Participants without an evaluable baseline result were assumed to have a baseline modified Bauermeister score of 0.

Outcome measures

Outcome measures
Measure	Romiplostim n=27 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.	Cohort 2 n=36 Participants Participants enrolled under the protocol supplement in the EU, Switzerland, or Turkey received weekly romiplostim for 3 years and had a bone marrow biopsy at baseline and year 2.
Percentage of Participants With Increased Modified Bauermeister Grade	3.7 percentage of participants Interval 0.1 to 19.0	0.0 percentage of participants Interval 0.0 to 9.7

PRIMARY outcome

Timeframe: Year 1 (Cohort 1) and year 2 (Cohort 2)

Population: Bone marrow analysis set participants with an on-study bone marrow abnormality assessment

The percentage of participants with bone marrow abnormalities (eg, myelodysplastic syndrome, monosomy 7) based on analysis of bone marrow biopsy and aspirate samples using cytogenetics and fluorescence in situ hybridization.

Outcome measures

Outcome measures
Measure	Romiplostim n=27 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.	Cohort 2 n=31 Participants Participants enrolled under the protocol supplement in the EU, Switzerland, or Turkey received weekly romiplostim for 3 years and had a bone marrow biopsy at baseline and year 2.
Percentage of Participants Who Developed Bone Marrow Abnormalities	0.0 percentage of participants Interval 0.0 to 12.8	0.0 percentage of participants Interval 0.0 to 11.2

SECONDARY outcome

Timeframe: From week 2 to the end of the treatment period, 36 months

Population: Efficacy analysis set

Platelet response was defined as a platelet count of ≥ 50 x 10⁹/L with no rescue medication use in the past 4 weeks. Monthly platelet response was calculated based on the median platelet count during each month. For each participant, the percentage of time with platelet response was calculated as the number of months a platelet response was observed divided by the total number of months response was assessed.

Outcome measures

Outcome measures
Measure	Romiplostim n=203 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.	Cohort 2 Participants enrolled under the protocol supplement in the EU, Switzerland, or Turkey received weekly romiplostim for 3 years and had a bone marrow biopsy at baseline and year 2.
Percentage of Time With a Platelet Response During the Overall Treatment Period	78.21 percentage of time Interval 26.67 to 90.39	—

SECONDARY outcome

Timeframe: Baseline and from week 2 to month 36

Population: Efficacy analysis set

The percentage of time with an increase in platelet count ≥ 20 x 10⁹ cells/L above baseline from week 2 until the end of the treatment period without rescue medication use within the past 4 weeks. For each participant, the percentage of time with an increase in platelet count ≥ 20 x10⁹ cells/L above baseline was calculated as the number of months the median platelet count was ≥ 20 x10⁹ cells/L above baseline divided by the total number of months assessed.

Outcome measures

Outcome measures
Measure	Romiplostim n=203 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.	Cohort 2 Participants enrolled under the protocol supplement in the EU, Switzerland, or Turkey received weekly romiplostim for 3 years and had a bone marrow biopsy at baseline and year 2.
Percentage of Time With an Increase in Platelet Count ≥ 20 x 10⁹ Cells/L Above Baseline	80.13 percentage of time Interval 39.13 to 92.31	—

SECONDARY outcome

Timeframe: From first dose of romiplostim to the end of the treatment period, 36 months

Population: Efficacy analysis set

Rescue medication is defined as any medication or transfusion, other than romiplostim and excluded medications, that is administered after enrollment to the participant with the intent of raising platelet counts or to prevent bleeding and includes concomitant medications for ITP in which the dose and/or schedule was increased. Permitted rescue medications included the following: * corticosteroids * platelet transfusions * Intravenous immunoglobulin (IVIG) * azathioprine * anti-D immunoglobulin * danazol

Outcome measures

Outcome measures
Measure	Romiplostim n=203 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.	Cohort 2 Participants enrolled under the protocol supplement in the EU, Switzerland, or Turkey received weekly romiplostim for 3 years and had a bone marrow biopsy at baseline and year 2.
Number of Participants Reporting Use of Rescue Medications for ITP During the Treatment Period	60 Participants	—

SECONDARY outcome

Timeframe: Week 12, week 52 and every 24 weeks thereafter up to month 36

Population: Participants who received at least 1 dose of romiplostim and with a post-baseline antibody result.

Blood samples were first tested for the presence of binding antibodies to romiplostim or the peptide portion of romiplostim, and to endogenous thrombopoietin (eTPO). Samples testing positive for binding antibodies were then tested for neutralizing antibodies by assessing their ability to neutralize romiplostim and/or eTPO in a cell-based bioassay. Participants who developed neutralizing antibodies are those who had a postbaseline positive result with a negative or no result at baseline. Transient is defined as a negative result at the participant's last time point tested within the study period.

Outcome measures

Outcome measures
Measure	Romiplostim n=203 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.	Cohort 2 Participants enrolled under the protocol supplement in the EU, Switzerland, or Turkey received weekly romiplostim for 3 years and had a bone marrow biopsy at baseline and year 2.
Number of Participants Who Developed Anti-Romiplostim or Anti-Thrombopoietin Neutralizing Antibodies Anti-romiplostim neutralizing antibodies	7 Participants	—
Number of Participants Who Developed Anti-Romiplostim or Anti-Thrombopoietin Neutralizing Antibodies Transient anti-romiplostim neutralizing antibodies	4 Participants	—
Number of Participants Who Developed Anti-Romiplostim or Anti-Thrombopoietin Neutralizing Antibodies Anti-eTPO neutralizing antibodies	1 Participants	—
Number of Participants Who Developed Anti-Romiplostim or Anti-Thrombopoietin Neutralizing Antibodies Transient anti-eTPO neutralizing antibodies	1 Participants	—

SECONDARY outcome

Timeframe: SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months).

Population: Participants who received at least 1 dose of romiplostim

An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant, which does not necessarily have a causal relationship with study treatment. A serious adverse event (SAE) was defined as an AE that met at least 1 of the following criteria: * fatal * life threatening * required in-patient hospitalization or prolongation of existing hospitalization * resulted in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event Adverse events were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grading scale, where Grade 1 = mild AE; Grade 2 = moderate AE; Grade 3 = severe AE; Grade 4 = life-threatening or disabling; Grade 5 = death related to AE.

Outcome measures

Outcome measures
Measure	Romiplostim n=203 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.	Cohort 2 Participants enrolled under the protocol supplement in the EU, Switzerland, or Turkey received weekly romiplostim for 3 years and had a bone marrow biopsy at baseline and year 2.
Number of Participants With Adverse Events Any adverse event (AE)	193 Participants	—
Number of Participants With Adverse Events Serious adverse events (SAE)	60 Participants	—
Number of Participants With Adverse Events AEs leading to discontinuation of romiplostim	15 Participants	—
Number of Participants With Adverse Events Adverse event Grade ≥ 3	66 Participants	—
Number of Participants With Adverse Events Adverse event Grade ≥ 4	19 Participants	—
Number of Participants With Adverse Events Adverse event Grade ≥ 5	0 Participants	—
Number of Participants With Adverse Events Treatment-related adverse events (TRAE)	56 Participants	—
Number of Participants With Adverse Events Treatment-related serious adverse events	8 Participants	—
Number of Participants With Adverse Events TRAEs leading to discontinuation of romiplostim	8 Participants	—
Number of Participants With Adverse Events Treatment-related adverse events Grade ≥ 3	8 Participants	—
Number of Participants With Adverse Events Treatment-related adverse events Grade ≥ 4	0 Participants	—
Number of Participants With Adverse Events Treatment-related adverse events Grade ≥ 5	0 Participants	—

SECONDARY outcome

Timeframe: Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)

The percentage of participants with increased reticulin as evidenced by silver staining and defined as any increase from baseline in the modified Bauermeister grade: Grade 0: No reticulin fibers demonstrable Grade 1: Occasional fine individual fibers and foci of a fine fiber network Grade 2: Fine fiber network throughout most of the section; no coarse fibers Grade 3: Diffuse fiber network with scattered thick coarse fibers but no mature collagen (negative to trichrome staining) Grade 4: Diffuse, often course fiber network with areas of collagenization (positive trichrome staining) Participants without an evaluable baseline result were assumed to have a baseline modified Bauermeister score of 0.

Outcome measures

Outcome measures
Measure	Romiplostim n=27 Participants Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.	Cohort 2 n=36 Participants Participants enrolled under the protocol supplement in the EU, Switzerland, or Turkey received weekly romiplostim for 3 years and had a bone marrow biopsy at baseline and year 2.
Percentage of Participants Who Developed Increased Reticulin	18.5 percentage of participants Interval 6.3 to 38.1	47.2 percentage of participants Interval 30.4 to 64.5

Adverse Events

Romiplostim

Serious events: 60 serious events

Other events: 183 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Romiplostim n=203 participants at risk Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.
Blood and lymphatic system disorders Anaemia	0.99% 2/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Evans syndrome	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Haemorrhagic disorder	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Immune thrombocytopenic purpura	1.5% 3/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Lymphadenitis	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	2.0% 4/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenic purpura	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Cardiac disorders Supraventricular tachycardia	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	0.99% 2/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Gingival bleeding	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Haematemesis	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Mouth haemorrhage	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Tooth impacted	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Appendicitis	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Cytomegalovirus infection	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Gastroenteritis rotavirus	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Influenza	0.99% 2/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Otitis externa	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Otitis media acute	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Peritonsillar abscess	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Pilonidal cyst	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Pneumonia	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Staphylococcal abscess	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Head injury	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Road traffic accident	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Arthroscopy	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Blood urine present	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Neutralising antibodies positive	2.0% 4/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Investigations Platelet count decreased	4.9% 10/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Haemarthrosis	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Mixed connective tissue disease	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Nervous system disorders Headache	0.99% 2/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Nervous system disorders Presyncope	0.99% 2/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Psychiatric disorders Suicidal ideation	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Renal and urinary disorders Haematuria	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Renal and urinary disorders Lupus nephritis	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Reproductive system and breast disorders Gynaecomastia	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Reproductive system and breast disorders Menorrhagia	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Reproductive system and breast disorders Metrorrhagia	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Reproductive system and breast disorders Polymenorrhoea	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Reproductive system and breast disorders Varicocele	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.9% 12/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Ecchymosis	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Petechiae	0.99% 2/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Purpura	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Vascular disorders Haemorrhage	0.49% 1/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	Romiplostim n=203 participants at risk Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.
Blood and lymphatic system disorders Anaemia	6.4% 13/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Ear and labyrinth disorders Ear pain	7.4% 15/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	14.3% 29/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain upper	19.2% 39/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	18.7% 38/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Gingival bleeding	10.3% 21/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Mouth haemorrhage	7.9% 16/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	18.2% 37/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	23.2% 47/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
General disorders Fatigue	9.4% 19/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
General disorders Pyrexia	32.0% 65/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Immune system disorders Hypersensitivity	5.9% 12/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Conjunctivitis	6.4% 13/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Ear infection	7.4% 15/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Gastroenteritis	9.4% 19/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Influenza	8.9% 18/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	36.9% 75/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Pharyngitis	15.8% 32/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Rhinitis	19.7% 40/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Tonsillitis	7.4% 15/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	19.2% 39/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Viral infection	10.3% 21/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Contusion	19.7% 40/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	6.4% 13/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Skin laceration	5.9% 12/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	11.3% 23/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	10.8% 22/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Nervous system disorders Dizziness	6.9% 14/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Nervous system disorders Headache	38.4% 78/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	25.6% 52/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	37.9% 77/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.9% 18/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	18.2% 37/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	13.3% 27/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Ecchymosis	9.4% 19/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Petechiae	23.6% 48/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	13.3% 27/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Vascular disorders Haematoma	20.7% 42/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Infections and infestations Sinusitis	5.4% 11/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Limb injury	5.4% 11/203 • SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months). All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER