Trial Outcomes & Findings for Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric PIDD Subjects (NCT NCT03116347)

Results Overview

An Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any severe related TEAEs (excluding infections) was reported.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

42 participants

Primary outcome timeframe

From start of study drug administration up to 20 months

Results posted on

2023-01-11

Participant Flow

The study was conducted at 16 sites from 30 May 2017 to 15 January 2021. A total of 42 participants were enrolled and treated in this study. This study consisted of 3 treatment periods: Epoch 1, Epoch 2 and Epoch 3. Participant with anti-rHuPH20 antibody titer greater than or equal to (\>=) 160 during Epoch 1 or Epoch 2 and who experienced either a related serious adverse event or related severe adverse event were followed to Epoch 3.

Participants who were treated with HyQvia in Epoch 1 followed by Epoch 2 were referred to as "HyQvia new starters" and participants who started directly in Epoch 2 were referred to as "HyQvia pre-treated". 1 participant from "HyQvia new starters" group discontinued Epoch 2 and entered Epoch 3 due to a severe related adverse event. Participant did not receive HyQvia treatment in Epoch 3. Therefore, no further safety and efficacy data were collected in Epoch 3.

Participant milestones

Participant milestones
Measure	HyQvia New Starters Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia subcutaneously (SC) with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Overall Study STARTED	23	19
Overall Study Started Epoch 1	23	0
Overall Study Completed Epoch 1	22	0
Overall Study Started Epoch 2	22	19
Overall Study Completed Epoch 2	22	17
Overall Study Moved From Epoch 2 to Epoch 3	1	0
Overall Study Completed Epoch 3	1	0
Overall Study COMPLETED	22	17
Overall Study NOT COMPLETED	1	2

Reasons for withdrawal

Reasons for withdrawal
Measure	HyQvia New Starters Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia subcutaneously (SC) with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Overall Study Withdrawal by Subject	1	2

Baseline Characteristics

Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric PIDD Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.	Total n=42 Participants Total of all reporting groups
Age, Continuous	10.3 Years STANDARD_DEVIATION 3.82 • n=5 Participants	11.7 Years STANDARD_DEVIATION 4.33 • n=7 Participants	11 Years STANDARD_DEVIATION 4.07 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	23 Participants n=5 Participants	19 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	22 Participants n=5 Participants	19 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

An Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any severe related TEAEs (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections)	1 Participants	0 Participants

PRIMARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

An AE was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Severe related TEAEs rate per infusion was calculated as number of severe related TEAEs/total number of infusions administered to participants in the analysis set. Rate of any severe related TEAEs per infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusions Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusions Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of Any Severe Related TEAEs Per Infusion (Excluding Infections)	0.004 Number of Severe Related TEAEs/Infusion	0 Number of Severe Related TEAEs/Infusion

PRIMARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any related serious TEAEs per infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Any Related Serious TEAEs Per Infusion (Excluding Infections)	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in-patient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Rate of related serious TEAEs per infusion was calculated as number of related serious TEAEs/total number of infusions administered to participants in the analysis set. Rate of any related serious TEAEs per Infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of Any Related Serious TEAEs Per Infusion (Excluding Infections)	0 Number of Related Serious TEAEs/Infusion	0 Number of Related Serious TEAEs/Infusion

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: Full analysis set included all participants who provide informed consent and meet enrollment eligibility. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.

Change from baseline in total serum trough levels of IgG in Epoch 1 and 2 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=20 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=17 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Efficacy: Change From Baseline in Total Serum Trough Levels of Immunoglobulin G (IgG) at Month 12	0.035 Gram per liter (g/L) Standard Deviation 1.6983	-0.709 Gram per liter (g/L) Standard Deviation 2.6576

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.

Change from baseline in Serum trough levels of IgG subclasses 1, 2, 3, and 4 in Epoch 1 and 2 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=16 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=15 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 IgG Subclass 1 : Changed at Month 12	-0.813 g/L Standard Deviation 1.1087	-0.467 g/L Standard Deviation 1.5976
Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 IgG Subclass 2 : Changed at Month 12	0.000 g/L Standard Deviation 0.8944	-0.667 g/L Standard Deviation 1.3452
Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 IgG Subclass 3 : Changed at Month 12	0.000 g/L Standard Deviation 0.3651	0.133 g/L Standard Deviation 0.3519
Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 IgG Subclass 4 : Changed at Month 12	0.094 g/L Standard Deviation 0.0854	-0.027 g/L Standard Deviation 0.0799

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. Specific antibody data were not scheduled to be collected at Epoch 2 Month 0, so for most participants baseline could not be defined and change from baseline was not reported in HYQVIA Pre-treated arm.

Change from baseline in trough levels of specific antibodies in clostridium tetani toxoid IgG at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. Here, IU/ml was defined as "International units per milliliter".

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=21 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Clostridium Tetani Toxoid IgG at Month 12	-0.218 IU/ml Standard Deviation 0.9345	—

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. Specific antibody data were not scheduled to be collected at Epoch 2 Month 0, so for most participants baseline could not be defined and change from baseline was not reported in HYQVIA Pre-treated arm.

Change from baseline in trough levels of specific antibodies in HBV at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=16 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Hepatitis B Virus (HBV) at Month 12	167.875 International units per liter (IU/L) Standard Deviation 147.4887	—

SECONDARY outcome

Timeframe: Baseline, Month 12

Population: All participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, "Overall number of Participants Analyzed" signifies participants who were evaluable for this outcome measure. Specific antibody data were not scheduled to be collected at Epoch 2 Month 0, so for most participants baseline could not be defined and change from baseline was not reported in HYQVIA Pre-treated arm.

Change from baseline in trough levels of specific antibodies in Haemophilus influenzae B IgG at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=20 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Haemophilus Influenzae B IgG at Month 12	-0.017 Milligram per liter (mg/L) Standard Deviation 0.9503	—

SECONDARY outcome

Timeframe: Up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Percentage of participants who achieved a treatment interval of three or four weeks in Epoch 2 was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 Every 3 weeks treatment interval	39.1 Percentage of participants	15.8 Percentage of participants
Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 Every 4 weeks treatment interval	60.9 Percentage of participants	84.2 Percentage of participants

SECONDARY outcome

Timeframe: Up to 12 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Percentage of participants who maintained a treatment interval of three or four weeks in Epoch 2 up to 12 months was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 up to 12 Months	87.0 Percentage of participants	78.9 Percentage of participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Number of Participants with local TEAEs (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Local TEAEs (Excluding Infections)	11 Participants	3 Participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Rate of local TEAEs per infusion was calculated as number of local adverse events/total number of infusions administered to participants in the analysis set. Only events are included which start prior to participants start date of non-response. Rate of local TEAEs per infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of Local TEAEs Per Infusion (Excluding Infections)	0.082 Number of local TEAEs/Infusion	0.009 Number of local TEAEs/Infusion

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with local adverse reactions (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Local Adverse Reaction (Excluding Infections)	11 Participants	3 Participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Rate of local adverse reaction per infusion was calculated as number of local adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of local adverse reactions per infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of Local Adverse Reaction Per Infusion (Excluding Infections)	0.080 Number of Local AR events/Infusion	0.009 Number of Local AR events/Infusion

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Number of participants with systemic TEAEs (excluding infections) was reported..

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Systemic TEAEs (Excluding Infections)	15 Participants	10 Participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Rate of systemic TEAEs per infusion was calculated as number of systemic adverse events/total number of infusions administered to participants in the analysis set. Rate of systemic TEAEs per infusion was assessed based on events per infusion.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of Systemic TEAEs Per Infusion (Excluding Infections)	0.138 Number of systemic TEAEs/Infusion	0.142 Number of systemic TEAEs/Infusion

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with systemic adverse reaction (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Systemic Adverse Reaction (Excluding Infections)	3 Participants	1 Participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Rate of Systemic adverse reactions per infusion was calculated as number of systemic adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of systemic adverse reactions per infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of Systemic Adverse Reaction Per Infusion (Excluding Infections)	0.011 Number of systemic AR events/Infusion	0.012 Number of systemic AR events/Infusion

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Number of participants with any TEAEs (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Any TEAEs (Excluding Infections)	18 Participants	11 Participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Rate of TEAEs per infusion was calculated as number of adverse events/total number of infusions administered to participants in the analysis set. Rate of TEAEs per infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of TEAEs Per Infusion (Excluding Infections)	0.220 Number of TEAEs/Infusion	0.151 Number of TEAEs/Infusion

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with any adverse reactions (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Any Adverse Reactions (Excluding Infections)	12 Participants	3 Participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Rate of all adverse reactions per infusion was calculated as number of adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of any adverse reactions per infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of Any Adverse Reaction Per Infusion (Excluding Infections)	0.091 Adverse reaction event/Infusion	0.021 Adverse reaction event/Infusion

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Number of participants with any temporally associated TEAEs (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Any Temporally Associated TEAEs (Excluding Infections)	13 Participants	6 Participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Rate of any temporally associated TEAEs per infusion was calculated as number of temporally associated adverse events/total number of infusions administered to participants in the analysis set. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Rate of any temporally associated TEAEs per infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of Any Temporally Associated TEAEs Per Infusion (Excluding Infections)	0.106 Temporally associated TEAEs/Infusion	0.027 Temporally associated TEAEs/Infusion

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia

Number of participants with any related (causally) and/or temporally associated TEAEs (excluding infections) was reported. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Any Related (Causally) and/or Temporally Associated TEAEs (Excluding Infections)	13 Participants	6 Participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Rate of any related (causally) and/or temporally associated TEAEs per infusion was calculated as number of related and/or temporally associated adverse events/ total number of infusions administered to participants in the analysis set. TEAEs recorded in the study database as "possibly related" or "probably related" to HYQVIA are considered HYQVIA-related adverse events. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Rate of any related (causally) and/or temporally associated TEAEs per infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of Any Related (Causally) and/or Temporally Associated TEAEs Per Infusion (Excluding Infections)	0.112 Related Temporally TEAEs/Infusion	0.033 Related Temporally TEAEs/Infusion

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Serious TEAE were the AEs that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in-patient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Number of participants with any serious TEAEs (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants With Any Serious TEAEs (Excluding Infections)	0 Participants	3 Participants

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Rate of serious TEAEs per infusion was calculated as number of serious adverse events/total number of infusions administered to participants in the analysis set. Rate of serious TEAEs per infusion (excluding infections) was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Rate of Serious TEAEs Per Infusion (Excluding Infections)	0 Number of serious TEAEs/Infusion	0.012 Number of serious TEAEs/Infusion

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Number of participants who developed positive titer (\>=160) of binding or neutralizing antibodies to rHuPH20 was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=23 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20 Participants with positive titer (>=160) of binding antibodies	0 Participants	0 Participants
Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20 Participants with neutralizing antibodies	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Number of infusions per month was calculated as total number of infusions per duration of treatment (days) \* 30.4 days per month.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusions Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusions Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Other Analysis: Number of Infusions Per Month	1.30 Infusion/Month Interval 1.1 to 1.7	1.20 Infusion/Month Interval 1.0 to 1.6

SECONDARY outcome

Timeframe: Up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Number of infusion sites (needle-sticks) per infusion was calculated as total number of infusion sites / total number of infusions. Only infusions with complete data available were included.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Infusion	1.65 Infusion sites (needle sticks)/Infusion Standard Deviation 0.442	1.25 Infusion sites (needle sticks)/Infusion Standard Deviation 0.403

SECONDARY outcome

Timeframe: Up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Number of infusion sites per month was calculated as total number of infusion sites / duration of treatment (days) \* 30.4 days. Only infusions with complete data available were included.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 infusion Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 infusion Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Month	1.96 Infusion sites (needle sticks)/Month Standard Deviation 0.780	1.33 Infusion sites (needle sticks)/Month Standard Deviation 0.634

SECONDARY outcome

Timeframe: From start of study drug administration up to 20 months.

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

The duration of infusion was defined as the difference between the end time and the start time of the HyQvia infusion.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=395 Infusions Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=247 Infusions Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Other Analysis: Duration of Infusion	75.0 Minutes Interval 10.0 to 215.0	101.0 Minutes Interval 15.0 to 257.0

SECONDARY outcome

Timeframe: Up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Maximum infusion rate per site was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=402 Infusions Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=265 Infusions Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Other Analysis: Maximum Infusion Rate Per Site	181.54 Milliliter per hour per site (mL/h/site) Standard Deviation 77.772	171.73 Milliliter per hour per site (mL/h/site) Standard Deviation 90.203

SECONDARY outcome

Timeframe: Up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Infusion volume per site was calculated as actual IgG volume (milliliter \[mL\]) / total number of infusion sites (hour) used.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=403 Infusions Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=286 Infusions Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Other Analysis: Infusion Volume Per Site	112.39 Milliliter per hour Standard Deviation 71.427	178.23 Milliliter per hour Standard Deviation 98.523

SECONDARY outcome

Timeframe: Up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.

Number of infusions that were interrupted or Stopped due to an AE was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=464 Infusions Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=331 Infusions Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE Number of infusions interrupted	4 Infusions	0 Infusions
Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE Number of infusions Stopped	1 Infusions	0 Infusions

SECONDARY outcome

Timeframe: Up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, "Overall number of Participants Analyzed" signifies participants who are evaluable for this outcome measure. Data collection and analysis was not planned for HyQvia pre-treated group.

Final dose interval, defined as three or four weeks infusion interval in Epoch 1 of treatment period, was reported.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=22 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Other Analysis: Number of Weeks to Reach Final 3 or 4-week Dose Interval in Epoch 1	6.10 Weeks Interval 3.0 to 7.0	—

SECONDARY outcome

Timeframe: Baseline up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, "Overall number of Participants Analyzed" signifies participants who are evaluable for this outcome measure and "Number analyzed" signifies participants who are evaluable for this outcome at specific time point.

PedsQL Generic Core Scale (GCS) was used for QOL assessment. It encompasses 4 dimensions (physical functioning \[PF\], emotional functioning \[EF\], social functioning \[SF\], school functioning \[ScF\]). Age groups are: Toddler (2-4 years), Young child (5-7 years), Child (8-12 years), and Teens (13-\<18 years). Depending on the participants age, the questionnaire may be completed by either the participant or the parent/caregiver as appropriate. For the Toddler group, the PedsQL GCS consisted of 21 items, using a 5-point Likert scale (0 to 4); for all other groups, the PedsQL consisted of 23 items, with a 3-point Likert scale (0, 2, 4) for the young child, and a 5-point Likert scale for the child and teens groups. All Scores were transformed on a scale from 0 to 100 where 0=100, 1=75, 2=50, 3=25, and 4=0. Higher scores indicate better quality of life. A negative change from baseline indicates worse quality of life. Baseline: last non-missing value before the initial dose of HYQVIA.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=5 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=8 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) PF in Toddler: Change up to 20 months	—	-3.12 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) PF in Young child: Change up to 20 months	—	-31.25 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) PF in Child: Change up to 20 months	7.81 Score on a scale Standard Deviation 6.626	-71.88 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) PF in Teens: Change up to 20 months	-12.65 Score on a scale Standard Deviation 12.726	13.75 Score on a scale Standard Deviation 24.664
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) EF in Toddler: Change up to 20 months	—	0.00 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) EF in Young child: Change up to 20 months	—	-25.00 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) EF in Child: Change up to 20 months	5.00 Score on a scale Standard Deviation 14.142	-20.00 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) EF in Teens: Change up to 20 months	-13.33 Score on a scale Standard Deviation 7.638	1.25 Score on a scale Standard Deviation 14.307
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) SF in Toddler: Change up to 20 months	—	0.00 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) SF in Young child: Change up to 20 months	—	-35.00 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) SF in Child: Change up to 20 months	-20.00 Score on a scale Standard Deviation 0.000	-40.00 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) SF in Teens: Change up to 20 months	1.67 Score on a scale Standard Deviation 7.638	8.00 Score on a scale Standard Deviation 11.511
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) ScF in Toddler: Change up to 20 months	—	25.00 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) ScF in Young child: Change up to 20 months	—	-45.00 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) ScF in Child: Change up to 20 months	-12.50 Score on a scale Standard Deviation 10.607	-65.00 Score on a scale Standard Deviation NA Here "NA" signifies standard deviation was not estimated due to single participant.
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) ScF in Teens: Change up to 20 months	1.67 Score on a scale Standard Deviation 7.638	-17.00 Score on a scale Standard Deviation 24.135

SECONDARY outcome

Timeframe: Baseline up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, "Overall number of Participants Analyzed" signifies participants who are evaluable for this outcome measure.

EQ-5D considered five attributes of quality of life evaluation, that is, mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each dimension had five possible levels: 1 (no problems); 2 (slight problems); 3 (moderate problems); 4 (severe problems), and; 5 (extreme problems). The participants rating of their current HRQoL state was recorded using a standard vertical 20-cm visual analog scale (EQ-VAS), which ranged from 0 to 100, where 0 indicated worst imaginable health state and 100 was best imaginable health state. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. A negative change from baseline indicates worse health state.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=5 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=7 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
HRQoL: Change From Baseline in EuroQoL (Quality of Life)-5 Dimensions (EQ-5D)	-8.60 Score on a scale Standard Deviation 11.149	-4.43 Score on a scale Standard Deviation 15.447

SECONDARY outcome

Timeframe: Baseline up to 20 months

Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, "Overall number of Participants Analyzed" signifies participants who are evaluable for this outcome measure and "Number analyzed" signifies participants who are evaluable for this outcome at specific time point.

TSQM-9 is a 9-item, validated, self-administered instrument to assess participants satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. The lowest possible score (1 for each item and 3 for all 3 subscales) was subtracted from the composite score and divided by the greatest possible score range. The greatest range was (7-1)\*3 items = 18 for the effectiveness and convenience, and (5-1)\*3 items = 12 for global satisfaction . The item scores of each of the 3 domains are summed and transformed to create a score of 0 (extremely dissatisfied) to 100 (extremely satisfied). Higher score indicated greater satisfaction in that domain. A negative change from baseline indicates less satisfaction in that domain. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.

Outcome measures

Outcome measures
Measure	HyQvia New Starters n=3 Participants Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=6 Participants Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Effectiveness: Change at 20 months	12.96 Score on a scale Standard Deviation 32.552	-0.92 Score on a scale Standard Deviation 10.783
HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Convenience: Change at 20 months	14.81 Score on a scale Standard Deviation 27.398	4.63 Score on a scale Standard Deviation 15.873
HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) Global satisfaction: Change 20 months	11.90 Score on a scale Standard Deviation 10.911	-2.38 Score on a scale Standard Deviation 19.518

Adverse Events

HyQvia New Starters

Serious events: 2 serious events

Other events: 22 other events

Deaths: 0 deaths

HyQvia Pre-treated

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	HyQvia New Starters n=23 participants at risk Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 participants at risk Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Eye disorders Idiopathic orbital inflammation	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Gastrointestinal disorders Dental caries	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Gastrointestinal disorders Inflammatory bowel disease	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
General disorders Pyrexia	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Pharyngitis	4.3% 1/23 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Pilonidal cyst	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Pneumonia	4.3% 1/23 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Acute sinusitis	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)

Other adverse events

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Publication restrictions are in place

Restriction type: OTHER

Measure	HyQvia New Starters n=23 participants at risk Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months.	HyQvia Pre-treated n=19 participants at risk Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.7% 2/23 • Number of events 4 • From start of study drug administration up to end of the study (up to 43 months)	10.5% 2/19 • Number of events 2 • From start of study drug administration up to end of the study (up to 43 months)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Blood and lymphatic system disorders Neutropenia	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Eye disorders Conjunctival haemorrhage	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Eye disorders Eye pain	4.3% 1/23 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Gastrointestinal disorders Diarrhoea	4.3% 1/23 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 5 • From start of study drug administration up to end of the study (up to 43 months)
Gastrointestinal disorders Inflammatory bowel disease	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Gastrointestinal disorders Vomiting	8.7% 2/23 • Number of events 4 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 2 • From start of study drug administration up to end of the study (up to 43 months)
General disorders Application site pruritus	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
General disorders Fatigue	13.0% 3/23 • Number of events 3 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 2 • From start of study drug administration up to end of the study (up to 43 months)
General disorders Infusion site erythema	8.7% 2/23 • Number of events 2 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
General disorders Infusion site pain	26.1% 6/23 • Number of events 11 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
General disorders Infusion site pruritus	17.4% 4/23 • Number of events 6 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
General disorders Pyrexia	13.0% 3/23 • Number of events 5 • From start of study drug administration up to end of the study (up to 43 months)	15.8% 3/19 • Number of events 7 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Acute sinusitis	4.3% 1/23 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Bacterial infection	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Bronchitis	8.7% 2/23 • Number of events 2 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Gastroenteritis	21.7% 5/23 • Number of events 7 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Gastroenteritis viral	8.7% 2/23 • Number of events 2 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Impetigo	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Lower respiratory tract infection	8.7% 2/23 • Number of events 3 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Nasopharyngitis	21.7% 5/23 • Number of events 6 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Otitis media	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Pharyngotonsillitis	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Pneumonia	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	10.5% 2/19 • Number of events 2 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Respiratory tract infection	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	10.5% 2/19 • Number of events 2 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Rhinitis	13.0% 3/23 • Number of events 4 • From start of study drug administration up to end of the study (up to 43 months)	31.6% 6/19 • Number of events 12 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Sinusitis	4.3% 1/23 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Upper respiratory tract infection	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	15.8% 3/19 • Number of events 3 • From start of study drug administration up to end of the study (up to 43 months)
Infections and infestations Viral infection	13.0% 3/23 • Number of events 4 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
Injury, poisoning and procedural complications Contusion	4.3% 1/23 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Injury, poisoning and procedural complications Radius fracture	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Investigations Blood immunoglobulin G decreased	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Nervous system disorders Headache	8.7% 2/23 • Number of events 3 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)
Respiratory, thoracic and mediastinal disorders Cough	34.8% 8/23 • Number of events 13 • From start of study drug administration up to end of the study (up to 43 months)	31.6% 6/19 • Number of events 12 • From start of study drug administration up to end of the study (up to 43 months)
Respiratory, thoracic and mediastinal disorders Epistaxis	8.7% 2/23 • Number of events 2 • From start of study drug administration up to end of the study (up to 43 months)	10.5% 2/19 • Number of events 6 • From start of study drug administration up to end of the study (up to 43 months)
Skin and subcutaneous tissue disorders Pruritus	8.7% 2/23 • Number of events 2 • From start of study drug administration up to end of the study (up to 43 months)	0.00% 0/19 • From start of study drug administration up to end of the study (up to 43 months)
Skin and subcutaneous tissue disorders Solar urticaria	0.00% 0/23 • From start of study drug administration up to end of the study (up to 43 months)	5.3% 1/19 • Number of events 1 • From start of study drug administration up to end of the study (up to 43 months)