Trial Outcomes & Findings for Validation of a Predictive Model of Response to Romiplostim in Patients With IPSS Low or Intermediate-1 Risk MDS and Thrombocytopenia (NCT NCT02335268)

Last Updated: 2023-08-16

Results Overview

The primary efficacy endpoint was the rate of HI-P defined as an absolute increase of platelet count to ≥ 30/nL for patients starting at \> 20/nL or an increase of platelets from \< 20/nL to \> 20/nL and by at least 100%, according to IWG 2006 criteria lasting for ≥ 8 weeks after at least 16 Weeks of romiplostim treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

77 participants

Primary outcome timeframe

after 4 months on therapy (week 16)

Results posted on

2023-08-16

Participant Flow

From May 2015 through July 2019, a total of 125 patients were screened at 19 study sites in France, 9 study sites in Germany and 1 study site in Czech Republic. Of them, 77 were eligible for study participation.

77 patients were assigned into two different model groups at the time of screening based on previous platelet transfusion events (PTE) and centrally assessed TPO serum levels. 51 patients were assigned to Group A (TPO \< 500 ng/L and PTE \< 6 units/past year) and 26 patients to Group B+C (TPO \> 500 ng/L, and/or PTE ≥ 6 units/past year).

Participant milestones

Participant milestones
Measure	Model Group A Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
Overall Study STARTED	51	26
Overall Study COMPLETED	34	20
Overall Study NOT COMPLETED	17	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Model Group A Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
Overall Study Physician Decision	5	1
Overall Study Lack of Efficacy	2	1
Overall Study Adverse Event	5	2
Overall Study increase blasts	2	0
Overall Study Withdrawal by Subject	3	2

Baseline Characteristics

Validation of a Predictive Model of Response to Romiplostim in Patients With IPSS Low or Intermediate-1 Risk MDS and Thrombocytopenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Model Group A n=51 Participants Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C n=26 Participants Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.	Total n=77 Participants Total of all reporting groups
Age, Continuous	72.6 years STANDARD_DEVIATION 10.3 • n=5 Participants	71.2 years STANDARD_DEVIATION 8.3 • n=7 Participants	72.1 years STANDARD_DEVIATION 9.6 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	10 Participants n=7 Participants	28 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	16 Participants n=7 Participants	49 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	49 Participants n=5 Participants	23 Participants n=7 Participants	72 Participants n=5 Participants
Race/Ethnicity, Customized Other	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Body Mass Index (BMI)	26.46 kg/m^2 STANDARD_DEVIATION 3.99 • n=5 Participants	28.03 kg/m^2 STANDARD_DEVIATION 4.44 • n=7 Participants	26.97 kg/m^2 STANDARD_DEVIATION 4.18 • n=5 Participants

PRIMARY outcome

Timeframe: after 4 months on therapy (week 16)

Outcome measures

Outcome measures
Measure	Model Group A n=34 Participants Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C n=22 Participants Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
Hematologic Improvement of Platelets (HI-P) After 4 Months on Therapy	71.75 platelets (/nL) Interval -15.5 to 342.5	18.75 platelets (/nL) Interval -25.0 to 161.0

SECONDARY outcome

Timeframe: week 16

Cumulative rate of hematologic improvement of platelets (HI-P), erythrocytes (HI-E) and neutrophil granulocytes (HI-N). None of the patients achieved simultaneous response of HI-P, HI-E and HI-N.

Outcome measures

Outcome measures
Measure	Model Group A n=51 Participants Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C n=26 Participants Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
Cumulative Hematologic Improvement yes	0 Participants	0 Participants
Cumulative Hematologic Improvement no	51 Participants	26 Participants

SECONDARY outcome

Timeframe: week 16

The incidence of disease progression to higher stage MDS or AML according to WHO (increase in blast percentage of ≥ 20 %)

Outcome measures

Outcome measures
Measure	Model Group A n=51 Participants Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C n=26 Participants Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
The Incidence of Disease Progression to Higher Stage MDS or AML yes	6 Participants	2 Participants
The Incidence of Disease Progression to Higher Stage MDS or AML no	45 Participants	24 Participants

SECONDARY outcome

Timeframe: week 16

Outcome measures

Outcome measures
Measure	Model Group A n=51 Participants Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C n=26 Participants Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
Increase of Peripheral Blasts During Therapy < 5%	31 Participants	15 Participants
Increase of Peripheral Blasts During Therapy 5%-10%	0 Participants	0 Participants
Increase of Peripheral Blasts During Therapy 10%-20%	0 Participants	0 Participants
Increase of Peripheral Blasts During Therapy > 20%	0 Participants	0 Participants
Increase of Peripheral Blasts During Therapy missing	20 Participants	11 Participants

SECONDARY outcome

Timeframe: week 16

Outcome measures

Outcome measures
Measure	Model Group A n=77 Participants Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
Association of the Presence of Certain Mutations With Disease Progression in a Retrospective Analysis no	69 Participants	—
Association of the Presence of Certain Mutations With Disease Progression in a Retrospective Analysis yes	8 Participants	—

SECONDARY outcome

Timeframe: up to 12 months

Outcome measures

Outcome measures
Measure	Model Group A n=51 Participants Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C n=24 Participants Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
Incidence of Bleeding Events	0.263 bleeding events per patient week Standard Deviation 0.476	0.249 bleeding events per patient week Standard Deviation 0.363

SECONDARY outcome

Timeframe: up to 12 months

Outcome measures

Outcome measures
Measure	Model Group A n=51 Participants Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C n=26 Participants Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
Type, Incidence and Severity of All Adverse Events Including Clinically Significant Changes in Laboratory Values	499 events	159 events

Adverse Events

Model Group A

Serious events: 12 serious events

Other events: 10 other events

Deaths: 0 deaths

Model Groups B+C

Serious events: 8 serious events

Other events: 5 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Model Group A n=51 participants at risk Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C n=26 participants at risk Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
Vascular disorders Hematoma	7.8% 4/51 • Number of events 4 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Vascular disorders Hypertension	3.9% 2/51 • Number of events 2 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Investigations Blast cells present	9.8% 5/51 • Number of events 5 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Respiratory, thoracic and mediastinal disorders Epistaxis	3.9% 2/51 • Number of events 2 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Blood and lymphatic system disorders Leukocytosis	13.7% 7/51 • Number of events 7 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Blood and lymphatic system disorders Anemia	3.9% 2/51 • Number of events 2 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Nervous system disorders Headache	3.9% 2/51 • Number of events 2 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
General disorders Chest pain	3.9% 2/51 • Number of events 2 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
General disorders Injection site hematoma	3.9% 2/51 • Number of events 2 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Gastrointestinal disorders Diarrhea	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Skin and subcutaneous tissue disorders Petechiae	9.8% 5/51 • Number of events 5 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Musculoskeletal and connective tissue disorders Arthralgia	3.9% 2/51 • Number of events 2 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Musculoskeletal and connective tissue disorders Pain in extremity	3.9% 2/51 • Number of events 2 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.

Additional Information

Dr. Carsta Köhler

GMIHO Gesellschaft für Medizinische Innovation - Hämatologie und Onkologie mbH

Phone: +49 351 25933

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Model Group A n=51 participants at risk Starting dose 750 µg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for responders treatment period was extended for up to 1 year (8 months extension period). The dose was adjusted based on the subject's platelet count.	Model Groups B+C n=26 participants at risk Starting dose 750 μg of romiplostim once a week (7d ± 2d), subcutaneous injection, 4 months maximum duration for non-responders. The dose was adjusted based on the subject's platelet count.
Vascular disorders Hemorrhage	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Surgical and medical procedures Central venous catheterization	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) AML	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oropharyngeal cancer	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
General disorders Asthenia	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
General disorders Mucosal hemorrhage	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
General disorders Pyrexia	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Reproductive system and breast disorders Testicular torsion	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Investigations Drug-specific antibody	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Investigations Monocyte count increased	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Investigations C-reactive protein increased	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Investigations Physical examination	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Cardiac disorders Angina unstable	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Cardiac disorders Atrial fibrillation	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Respiratory, thoracic and mediastinal disorders Lung infiltration	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Blood and lymphatic system disorders Febrile neutropenia	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Nervous system disorders Cerebrovascular accident	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Nervous system disorders Syncope	3.9% 2/51 • Number of events 2 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Gastrointestinal disorders Colitis	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Gastrointestinal disorders Gastrointestinal angiectasia	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Gastrointestinal disorders Hematochezia	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Gastrointestinal disorders Inguinal hernia	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Gastrointestinal disorders Intestinal mass	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Hepatobiliary disorders Cholecystitis	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Hepatobiliary disorders Cholelithiasis migration	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Hepatobiliary disorders Hepatic mass	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Renal and urinary disorders Hematuria	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Renal and urinary disorders Renal failure	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Skin and subcutaneous tissue disorders Purpura	0.00% 0/51 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	3.8% 1/26 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Musculoskeletal and connective tissue disorders Back pain	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Musculoskeletal and connective tissue disorders Bone pain	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Infections and infestations Viral rash	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Infections and infestations Anal abscess	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Infections and infestations Infection	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Infections and infestations Pneumonia	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.
Infections and infestations Tracheobronchitis	2.0% 1/51 • Number of events 1 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.	0.00% 0/26 • 16 weeks Patients were asked to each visit whether they have experienced AEs or SAEs.