Trial Outcomes & Findings for Study of rFVIIIFc for Immune Tolerance Induction (ITI) in Haemophilia A Patients With Inhibitors Who Have Failed Previous ITI Therapies (NCT NCT03103542)

Last Updated: 2024-09-19

Results Overview

Number of patients who achieve ITI success where ITI success is defined as achieving all 3 of the following criteria: * Negative titer for inhibitor (\<0.6 Bethesda units/mL by the Nijmegen-modified Bethesda assay) at 2 consecutive visits * FVIII incremental recovery (IR) \>66% of the expected IR at 2 consecutive visits * FVIII half-life (t½) ≥7 hours

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

16 participants

Primary outcome timeframe

up to 60 weeks

Results posted on

2024-09-19

Participant Flow

Recruitment was open at 18 sites in 9 countries in Northern America and Europe. 11 sites in 7 countries recruited patients. It was initially planned to enroll 20 patients but due to recruitment challenges and a changing treatment landscape the recruitment was stopped after enrolling 16 patients. Recruitment was open from Aug 2017 to Nov 2019. 18 patients were screened and 16 enrolled into this study.

After informed consent was provided, patients underwent study specific screening procedures. During the 4- to 6-week screening period, patients continued with their usual treatment regimen in accordance with the local standard of care. Patients who met all inclusion and no exclusion criteria specified by the protocol were enrolled into the study. The 2 screening failures did not meet inclusion criteria 1 (signed informed consent) and 5 (inhibitor titer ≥0.6 BU at screening) respectively.

Participant milestones

Participant milestones
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) Participants received rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who met the criteria for ITI success entered a tapering period of 16 weeks where the dose was tapered down until a prophylactic dose, as judged by the Investigator, was achieved and thereafter a follow-up period of 32 weeks where the patient continued to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Overall Study STARTED	16
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) Participants received rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who met the criteria for ITI success entered a tapering period of 16 weeks where the dose was tapered down until a prophylactic dose, as judged by the Investigator, was achieved and thereafter a follow-up period of 32 weeks where the patient continued to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Overall Study Physician Decision	2
Overall Study Adverse Event	2
Overall Study Other	2
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Study of rFVIIIFc for Immune Tolerance Induction (ITI) in Haemophilia A Patients With Inhibitors Who Have Failed Previous ITI Therapies

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Age, Categorical <=18 years	15 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	7.5 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	15 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	0 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants
Race/Ethnicity, Customized Race · American Indian or Alaska Native	0 Participants n=5 Participants
Region of Enrollment Canada	3 participants n=5 Participants
Region of Enrollment Sweden	1 participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants
Region of Enrollment Ireland	3 participants n=5 Participants
Region of Enrollment United Kingdom	3 participants n=5 Participants
Region of Enrollment Slovenia	1 participants n=5 Participants
Region of Enrollment Germany	4 participants n=5 Participants
Hemophilia history - severity Mild	0 Participants n=5 Participants
Hemophilia history - severity Moderate	0 Participants n=5 Participants
Hemophilia history - severity Severe	16 Participants n=5 Participants
Hemophilia history - Family history of Inhibitors Yes	7 Participants n=5 Participants
Hemophilia history - Family history of Inhibitors No	5 Participants n=5 Participants
Hemophilia history - Family history of Inhibitors Unknown	4 Participants n=5 Participants
Number of previous ITI Treatments 1 Treatment	10 Participants n=5 Participants
Number of previous ITI Treatments 2 Treatments	4 Participants n=5 Participants
Number of previous ITI Treatments 3 Treatments	2 Participants n=5 Participants
Inhibitor History - Historical Peak Titre Level	127.4 BU/ml n=5 Participants
Inhibitor history - Age at Inhibitor development	1.9 years STANDARD_DEVIATION 3.6 • n=5 Participants

PRIMARY outcome

Timeframe: up to 60 weeks

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
ITI Success ITI failure	6 Participants
ITI Success ITI success	1 Participants
ITI Success Partial Success	2 Participants
ITI Success Not determinable due to withdrawal during the ITI	7 Participants

SECONDARY outcome

Timeframe: up to 60 weeks

Population: 1 patient achieved ITI success and 2 patients achieved partial success

Time to the patient reaches ITI success according to the pre-defined criteria For the subset of patients who were classified as partial success at the end of the ITI period, the time to fulfillment of the criteria for partial success was also analyzed descriptively.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=3 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Time to ITI Success Time to ITI success	46.71 weeks Standard Deviation 0
Time to ITI Success Time to Partial Success	38.76 weeks Standard Deviation 15.05

SECONDARY outcome

Timeframe: Up to 48 weeks

Population: Only patients achieving ITI success are included in the analysis for this endpoint. 1 patient achieved ITI success.

Relapse was defined as a positive inhibitor (≥0.6 BU/mL) on 2 consecutive assessments and incremental recovery ≤66 % of the expected incremental recovery on 2 consecutive assessments

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=1 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Occurrence of Relapse During a 48-week Period Following Successful ITI Treatment	0 Participants

SECONDARY outcome

Timeframe: up to 60 weeks

Only bleeds requiring treatment with rFVIIIFc or bypassing agents should be registered. A bleeding episode starts from the first sign of a bleed and ends no more than 72 hours after the last injection of bypassing agents or rFVIIIFc to treat the bleeding episode.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Number of Bleedings During ITI Treatment	4.70 Annualized bleeding rate(bleedings/year) Interval 0.0 to 45.66

SECONDARY outcome

Timeframe: up to 48 weeks

Population: Only patients achieving ITI success are included in the analysis for this endpoint. 1 patient achieved ITI success.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=1 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Bleeding Rate During a 48-week Period Following Successful ITI Treatment	5.07 Annualized bleeding rate(bleedings/year) Interval 5.07 to 5.07

SECONDARY outcome

Timeframe: SAEs - approx 166 weeks AEs - approx 110 weeks

All observed adverse events as a measure of tolerability. (AE=adverse event, SAE=serious adverse event, TEAE=treatment emergent adverse event)

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Adverse Events (AEs) TEAEs	188 events
Adverse Events (AEs) Serious AEs	21 events
Adverse Events (AEs) Serious TEAEs	18 events
Adverse Events (AEs) Non-serious TEAEs	170 events
Adverse Events (AEs) Related TEAEs	2 events
Adverse Events (AEs) Mild AEs	145 events
Adverse Events (AEs) Moderate AEs	42 events
Adverse Events (AEs) Severe AEs	4 events
Adverse Events (AEs) AEs Leading to Withdrawal	3 events
Adverse Events (AEs) AEs Leading to Death	0 events

SECONDARY outcome

Timeframe: Up to 60 weeks

Consumption will be assessed based on amount of administered study treatment during the ITI period.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Consumption of rFVIIIFc	1902625.0 IU Interval 605000.0 to 7555750.0

SECONDARY outcome

Timeframe: Up to 60 weeks

Consumption will be assessed based on amount of administered study treatment during the ITI period.

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Consumption of rFVIIIFc	62586.7 IU/kg Interval 24226.7 to 89724.2

SECONDARY outcome

Timeframe: up to 60 weeks

Days missed school or work will be registered by the patients in an electronic diary

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Number of Days Missed School or Work During ITI Treatment	0.5 Days/year Interval 0.0 to 59.0

SECONDARY outcome

Timeframe: up to 60 weeks

Days missed school or work will be registered by the patients in an electronic diary

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Number of Days Missed School or Work During ITI Treatment	0.5 Days Interval 0.0 to 50.0

SECONDARY outcome

Timeframe: up to 48 weeks

Population: Only patients achieving ITI success are included in the analysis for this endpoint. 1 patient achieved ITI success.

Days missed school or work will be registered by the patients in an electronic diary

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=1 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Number of Days Missed School or Work During a 48-week Period Following Successful ITI Treatment	0 Days Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: up to 60 weeks

Days of hospitalization will be collected by the Investigator at the study visits

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Number of Hospitalizations During ITI Treatment	0 Days Interval 0.0 to 36.0

SECONDARY outcome

Timeframe: Up to 48 weeks

Population: Only patients achieving ITI success are included in the analysis for this endpoint. 1 patient achieved ITI success.

Days of hospitalization will be collected by the Investigator at the study visits

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=1 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Number of Hospitalizations During a 48-week Period Following Successful ITI Treatment	0 Days

SECONDARY outcome

Timeframe: up to 108 weeks

Population: 16 patients analyzed for the ITI period. 1 patient analyzed for the tapering and follow-up period (1 patient achieved ITI success and entered tapering and follow-up periods).

Defined as percentage of administered doses versus planned doses

Outcome measures

Outcome measures
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 Participants Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Adherence ITI period	92.52 % of administered vs planned doses Standard Deviation 13.86
Adherence Tapering period	100.5 % of administered vs planned doses Standard Deviation 0
Adherence Follow-up period	98.56 % of administered vs planned doses Standard Deviation 0

Adverse Events

Recombinant Coagulation Factor VIII Fc (rFVIIIFc)

Serious events: 7 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 participants at risk Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Vascular disorders Brachiocephalic vein thrombosis	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Vascular disorders Vena cava thrombosis	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Vascular disorders Thrombosis	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Blood and lymphatic system disorders Immune thrombocytopenic purpura	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Blood and lymphatic system disorders Spontaneous haemorrhage	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Nervous system disorders Headache	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
General disorders Pyrexia	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Renal and urinary disorders Haematuria	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Product Issues Thrombosis in device	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Haemarthrosis	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Tonsillitis	12.5% 2/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Vascular device infection	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Device related infection	6.2% 1/16 • Number of events 5 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Device related sepsis	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Staphylococcal infection	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.

Other adverse events

Other adverse events
Measure	Recombinant Coagulation Factor VIII Fc (rFVIIIFc) n=16 participants at risk Participants will receive rFVIIIFc at a dose of 200 international units (IU)/kilogram (kg) as once daily injections or divided on several injections per day at the discretion of the Investigator, starting at baseline visit up to maximum of 60 Weeks during the ITI Period. Participants who meet the criteria for ITI success will enter a tapering period of 16 weeks where the dose will be tapered down until a prophylactic dose, as judged by the Investigator, is achieved and thereafter a follow-up period of 32 weeks where the patient will continue to receive prophylactic treatment with rFVIIIFc. Recombinant coagulation factor (rFVIIIFc): rFVIIIFc 200 IU/kg/day during ITI Period and thereafter adjusted according to the Investigator's judgement administered intravenously.
Vascular disorders Haemorrhage	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Immune system disorders Seasonal allergy	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
General disorders Catheter site irritation	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
General disorders Gait disturbance	6.2% 1/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
General disorders Influenza like illness	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
General disorders Peripheral swelling	6.2% 1/16 • Number of events 4 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
General disorders Pyrexia	6.2% 1/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Psychiatric disorders Anxiety	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Psychiatric disorders Autism spectrum disorder	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Injury, poisoning and procedural complications Arthropod bite	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Injury, poisoning and procedural complications Contusion	6.2% 1/16 • Number of events 15 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Injury, poisoning and procedural complications Fall	18.8% 3/16 • Number of events 4 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Injury, poisoning and procedural complications Skin abrasion	6.2% 1/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Injury, poisoning and procedural complications Skin laceration	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Injury, poisoning and procedural complications Thermal burn	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Injury, poisoning and procedural complications Tongue injury	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Injury, poisoning and procedural complications Traumatic haematoma	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Injury, poisoning and procedural complications Traumatic haemorrhage	6.2% 1/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Activated partial thromboplastin time prolonged	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Blood alkaline phosphatase increased	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Blood urine present	12.5% 2/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Haematocrit decreased	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Haemoglobin decreased	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Human rhinovirus test positive	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Protein urine present	6.2% 1/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Red blood cell count decreased	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Tri-iodothyronine free increased	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Urine ketone body present	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations White blood cell count decreased	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Respiratory, thoracic and mediastinal disorders Cough	25.0% 4/16 • Number of events 4 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Oropharyngeal pain	6.2% 1/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Investigations Rhinorrhoea	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Blood and lymphatic system disorders Anaemia	12.5% 2/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Blood and lymphatic system disorders Iron deficiency anaemia	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Blood and lymphatic system disorders Lymphadenopathy	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Blood and lymphatic system disorders Spontaneous haemorrhage	6.2% 1/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Nervous system disorders Dizziness	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Nervous system disorders Headache	31.2% 5/16 • Number of events 7 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Nervous system disorders Jugular vein occlusion	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Nervous system disorders Migraine	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Eye disorders Visual impairment	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Ear and labyrinth disorders Ear pain	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Abdominal pain	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Abdominal pain lower	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Abdominal pain upper	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Anal incontinence	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Constipation	6.2% 1/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Diarrhoea	12.5% 2/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Lip ulceration	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Loose tooth	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Mouth ulceration	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Tooth development disorder	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Gastrointestinal disorders Vomiting	18.8% 3/16 • Number of events 3 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Skin and subcutaneous tissue disorders Acne	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Skin and subcutaneous tissue disorders Dermatitis contact	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Skin and subcutaneous tissue disorders Eczema	12.5% 2/16 • Number of events 3 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Skin and subcutaneous tissue disorders Onychomadesis	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Skin and subcutaneous tissue disorders Petechiae	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Skin and subcutaneous tissue disorders Red man syndrome	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Product Issues Thrombosis in device	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Product Issues Device damage	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Arthralgia	31.2% 5/16 • Number of events 9 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Arthropathy	6.2% 1/16 • Number of events 3 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Back pain	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Growing pains	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Haemarthrosis	6.2% 1/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Joint swelling	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Mobility decreased	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	18.8% 3/16 • Number of events 3 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Pain in extremity	18.8% 3/16 • Number of events 4 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Posture abnormal	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Musculoskeletal and connective tissue disorders Soft tissue swelling	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Metabolism and nutrition disorders Vitamin D deficiency	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Adenovirus infection	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Conjunctivitis	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Fungal skin infection	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Gastroenteritis	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Gastrointestinal infection	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Impetigo	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Influenza	6.2% 1/16 • Number of events 2 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Nasopharyngitis	31.2% 5/16 • Number of events 10 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Rhinitis	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Tinea infection	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Upper respiratory tract infection	18.8% 3/16 • Number of events 4 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Varicella	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Viral infection	18.8% 3/16 • Number of events 5 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Infections and infestations Viral upper respiratory tract infection	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Renal and urinary disorders Haematuria	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.
Renal and urinary disorders Proteinuria	6.2% 1/16 • Number of events 1 • SAEs: From signature of the informed consent form to the safety follow-up visit (approximately 116 weeks). Non-serious AEs: From the time of first dose of IMP to the safety follow-up visit (approximately 110 weeks). The investigator were to report all directly observed adverse events, and all adverse events spontaneously reported by the patient. In addition, each patient were to be questioned about AEs at each study visit. AEs are reported on overall level. Please note the difference in the reporting period of SAEs and non-serious AEs (SAEs also collected during screening period). 18 patients entered screening, 16 patients were eventually enrolled and are included in the analysis.

Additional Information

Medical Information

Swedish Orphan Biovitrum AB

Phone: +468 6972000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60