Trial Outcomes & Findings for Long-Term Tolerability and Safety of HYQVIA/HyQvia in CIDP (NCT NCT02955355)

NCT ID: NCT02955355

Last Updated: 2024-08-28

Results Overview

An AE was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Treatment emergent adverse events (TEAEs) were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

85 participants

Primary outcome timeframe

From the first dose of study drug up to end of study (up to 6.6 years)

Results posted on

2024-08-28

Participant Flow

Participants took part in the study at 39 investigative sites worldwide from 14 November 2016 to 04 July 2023.

A total of 85 participants with a diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who completed Study 161403 (NCT02549170) without CIDP worsening were enrolled in this Extension Study to receive HYQVIA/HyQvia.

Participant milestones

Participant milestones
Measure
HYQVIA/HyQvia
Participants received HYQVIA/HyQvia (recombinant human hyaluronidase \[rHuPH20\] at a dose of 80 units per gram (U/g) immunoglobulin G \[IgG\], followed by subcutaneous \[SC\] immune globulin infusion \[IGI\] 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Overall Study
STARTED
85
Overall Study
COMPLETED
0
Overall Study
NOT COMPLETED
85

Reasons for withdrawal

Reasons for withdrawal
Measure
HYQVIA/HyQvia
Participants received HYQVIA/HyQvia (recombinant human hyaluronidase \[rHuPH20\] at a dose of 80 units per gram (U/g) immunoglobulin G \[IgG\], followed by subcutaneous \[SC\] immune globulin infusion \[IGI\] 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Overall Study
Adverse Event
4
Overall Study
Death
1
Overall Study
Physician Decision
21
Overall Study
Site Terminated by Sponsor
35
Overall Study
Withdrawal by Subject
19
Overall Study
Reason Not Specified
5

Baseline Characteristics

Long-Term Tolerability and Safety of HYQVIA/HyQvia in CIDP

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Age, Continuous
54.3 years
STANDARD_DEVIATION 13.11 • n=5 Participants
Sex: Female, Male
Female
39 Participants
n=5 Participants
Sex: Female, Male
Male
46 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
14 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
67 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
4 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
1 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=5 Participants
Race (NIH/OMB)
White
81 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
3 Participants
n=5 Participants
Height
171.5 centimeters (cm)
STANDARD_DEVIATION 10.98 • n=5 Participants
Weight
80.89 kilograms (kg)
STANDARD_DEVIATION 18.856 • n=5 Participants
Body Mass Index (BMI)
27.42 kilograms per meter square (kg/m^2)
STANDARD_DEVIATION 5.587 • n=5 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AE was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. Treatment emergent adverse events (TEAEs) were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants With Any Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs), Regardless of Causality
Any TEAE
76 Participants
Number of Participants With Any Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs), Regardless of Causality
Any Serious TEAE
20 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Causality was used to determine whether there was a reasonable possibility that the IP was etiologically related to/associated with the AE.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants With Causally Related Treatment-emergent SAEs and AEs
Any IP-Related TEAE
51 Participants
Number of Participants With Causally Related Treatment-emergent SAEs and AEs
Any IP-Related Serious TEAE
3 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Serious AR/SAR=any AR/SAR that is an untoward medical occurrence which at any dose meets one or more of following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect,is a medically important event,thromboembolic events,hemolytic anemia. Nonserious AR/SAR=AR/SAR that does not meet the criteria.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants With Adverse Reactions (ARs) or Suspected Adverse Reactions (SARs) Categorized as Serious and Non-serious
Any Serious AR/SAR
7 Participants
Number of Participants With Adverse Reactions (ARs) or Suspected Adverse Reactions (SARs) Categorized as Serious and Non-serious
Any Non-serious AR/SAR
57 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

Percentage of participants with TEAEs that may be a result of immune-mediated response to either immunoglobulin, rHuPH20, or other factors such as allergic reactions, immune complex-mediated reactions: local, complex-mediated reactions: systemic, thrombotic and embolic events were assessed. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. The percentage was rounded off to the nearest decimal.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Percentage of Participants With Treatment-Emergent Adverse Events That May be a Result of Immune-Mediated Responses
7.1 percentage of participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. AEs associated with an infusion are defined as AEs occurring after administration of IP (or any TEAE). Participants can have more than one TEAE associated with infusion.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Treatment-Emergent SAEs and AEs Associated With Infusions, Regardless of Causality
Serious TEAEs
30 events in participants
Number of Treatment-Emergent SAEs and AEs Associated With Infusions, Regardless of Causality
TEAEs
1406 events in participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. An SAE was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death, was life-threatening, required inpatient hospitalization or resulted in prolongation of an existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. AEs associated with an infusion are defined as AEs occurring after administration of IP (or any TEAE). Causality was used to determine whether there was a reasonable possibility that the IP was etiologically related to/associated with the AE.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Causally Related Treatment-Emergent SAEs and AEs Associated With Infusions
IP-Related Serious TEAEs
3 events in participants
Number of Causally Related Treatment-Emergent SAEs and AEs Associated With Infusions
IP-Related TEAEs
798 events in participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

TEAEs that occurred during infusion or within 72 hours post-infusion were considered to be temporally associated with infusions. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Participants can have more than one TEAE temporally associated with infusion.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of TEAEs Temporally Associated With Infusions
857 events in participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AR/SAR=any AE that meets any of following criteria: AE considered by either investigator and/or sponsor to be possibly or probably related to IP administration, begins during infusion of IP or within 72 hours following end of IP infusion,or AE for which causality assessment is missing or indeterminate. ARs/SARs associated with an infusion=AEs considered by the investigator to be occurring after administration of IP. Serious AR/SAR=any AR/SAR that is an untoward medical occurrence which at any dose meets one or more of following criteria: outcome is fatal/results in death, is life-threatening, requires inpatient hospitalization or results in prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect,is a medically important event,thromboembolic events,hemolytic anemia. Nonserious AR/SAR=AR/SAR that does not meet the criteria. Participants can have more than one AR/SAR associated with infusion.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Serious and Non-Serious ARs or SARs Associated With Infusions
Serious ARs/SARs
8 events in participants
Number of Serious and Non-Serious ARs or SARs Associated With Infusions
Non-Serious ARs/SARs
913 events in participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the Medical Dictionary for Regulatory Activities (MedDRA) Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Infusions associated with one or more AEs are defined as follows: if an AE occurs after an infusion but prior to the next infusion that infusion is associated with that AE.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=3487 infusions
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Infusions Associated With One or More Systemic TEAEs
50 infusions

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Infusions associated with one or more AEs are defined as follows: if an AE occurs after an infusion but prior to the next infusion that infusion is associated with that AE.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=3487 infusions
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Infusions Associated With One or More Local TEAEs
17 infusions

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=3487 infusions
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Intolerability and/or TEAEs
3 infusions

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per infusion was assessed at the group level calculated by dividing number of events by total number of infusions administered to participants in the Safety Analysis Set.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=3487 infusions
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Infusion
Systemic TEAEs
0.25 AEs/infusion
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Infusion
Local TEAEs
0.15 AEs/infusion

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per participant was assessed at the group level calculated by dividing number of events by total number of participants in the Safety Analysis Set.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Participant
Systemic TEAEs
10.38 AEs/participant
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Participant
Local TEAEs
6.16 AEs/participant

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Events per participant-years was calculated as follows: 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the Safety Analysis Set, divided by 365.25).

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year
Systemic TEAEs
4000.23 AEs/1000 participant-year
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year
Local TEAEs
2376.55 AEs/1000 participant-year

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". An adverse event that was "possibly related" or "probably related" to IP, or for which the relationship was unknown or missing, was considered as a "related AE". Data for number of events per infusion was assessed at the group level calculated by dividing number of events by total number of infusions administered to participants in the Safety Analysis Set.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=3487 infusions
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Infusion
Systemic IP-Related TEAEs
0.08 AEs/infusion
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Infusion
Local IP-Related TEAEs
0.15 AEs/infusion

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". An adverse event that was "possibly related" or "probably related" to IP, or for which the relationship was unknown or missing, was considered as a "related AE". Data for number of events per participant was assessed at the group level calculated by dividing number of events by total number of participants in the Safety Analysis Set.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Participant
Systemic IP-Related TEAEs
3.38 AEs/participant
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Participant
Local IP-Related TEAEs
6.01 AEs/participant

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. Systemic TEAEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local TEAEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". An adverse event that was "possibly related" or "probably related" to IP, or for which the relationship was unknown or missing, was considered as a "related AE". Events per participant-years was calculated as follows: 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the Safety Analysis Set, divided by 365.25).

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per 1000 Participant-year
Systemic IP-Related TEAEs
1301.66 AEs/1000 participant-year
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per 1000 Participant-year
Local IP-Related TEAEs
2317.59 AEs/1000 participant-year

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Systemic AEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local AEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per infusion was assessed at the group level calculated by dividing number of events by total number of infusions administered to participants in the Safety Analysis Set.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=3487 infusions
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Infusion
Systemic ARs/SARs
0.11 reactions/infusion
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Infusion
Local ARs/SARs
0.15 reactions/infusion

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Systemic AEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local AEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Data for number of events per participant was assessed at the group level calculated by dividing number of events by total number of participants in the Safety Analysis Set.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Participant
Systemic ARs/SARs
4.58 reactions/participant
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Participant
Local ARs/SARs
6.16 reactions/participant

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AR plus SAR is any AE that meets any of the following criteria: an AE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or that begins during infusion of IP or within 72 hours following the end of IP infusion, or AE for which causality assessment is missing or indeterminate. Systemic AEs were defined as AEs that were not included in the MedDRA Higher Level Group Term "administration site reactions" and did not contain the phrase "injection site". Local AEs were defined as AEs that were included in the MedDRA Higher Level Group Term "administration site reactions" or contained the phrase "injection site" or "infection site". Events per participant-years was calculated as follows: 1000 x (number of events / total number of days of exposure, i.e., the sum of duration of treatment for all participants in the Safety Analysis Set, divided by 365.25).

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per 1000 Participant-year
Systemic ARs/SARs
1764.27 reactions/1000 participant-year
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per 1000 Participant-year
Local ARs/SARs
2376.55 reactions/1000 participant-year

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants With a TEAE That Led to Discontinuation From Study
4 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. A moderate or severe AE could be a result of immune-mediated response to either immunoglobulin, rHuPH20, or other factors such as allergic reactions, immune complex-mediated reactions: local, complex-mediated reactions: systemic, thrombotic and embolic events. The severity of each AE was assessed by the investigator using clinical expertise based on the following description: moderate=AE produces limited impairment of function and may require therapeutic intervention and produces no sequela/sequelae; severe=AE results in a marked impairment of function and may lead to temporary inability to resume usual life pattern and produces sequela/sequelae, which require (prolonged) therapeutic intervention.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants With Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses
3 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

An AE was defined as any untoward medical occurrence in a participant administered an IP that did not necessarily have a causal relationship with the treatment. TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. A moderate or severe AE could be a result of immune-mediated response to either immunoglobulin, rHuPH20, or other concomitant medications. The severity of each AE was assessed by the investigator using clinical expertise. Data for number of events per 100 infusions was assessed at the group level calculated by dividing number of events by total number of infusions and multiplying that by 100.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=3487 infusions
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Rate of Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses, Expressed as Number of Events Per 100 Infusions
0.0860 AEs/100 infusions

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

TEAEs were defined as adverse events that occurred during or after administration of the first dose of IP in this Extension Study. AE=any untoward medical occurrence in participant administered an IP that does not have causal relationship with treatment. Adverse reaction/suspected adverse reaction=AE that is considered by the investigator to be possibly or probably related to IP administration, or for which the causality is indeterminate or missing, or that begins during infusion of IP or within 72 hours following the end of IP infusion. All local infusion site treatment-emergent AEs were reported as adverse reactions.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants That Experienced Treatment-Emergent Local Infusion Site Reactions
30 Participants

PRIMARY outcome

Timeframe: During the ramp-up (8 weeks)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication. As prespecified in the statistical analysis plan (SAP), comparative local tolerability data for the ramp-up of 8 weeks from studies 161403 (for participants originally randomized to HYQVIA in double-blind) and 161505 were reported in the results of study 161505.

Participants with local tolerability events were those for which the infusion rate was reduced and/or the infusion was interrupted or stopped due to intolerability and/or AEs. These events were assessed during the initial ramp-up for each participant i.e., during the first 8 weeks of open-label extension study 161505 \[NCT02955355\] among participants originally randomized to placebo (as being in the placebo arm, they had no ramp-up during the 161403 \[NCT02549170\] study) versus during the 8-week ramp-up for participants originally randomized to active HYQVIA in double-blind 161403 study. Thus, the data for this outcome measure are presented per the bifurcation of participants in the study 161403.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=42 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
n=43 Participants
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants With Treatment-Emergent Local Tolerability Events During Ramp-up
6 Participants
13 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication. Overall number analyzed is the number of participants with local infusion reactions.

Local infusion reactions were defined as local (administration site-related) adverse events. Median infusion rate per site was derived as the median value across all participants, per participant's average infusion rate, by site: actual volume infused / duration in hours of infusion / number of sites. Median infusion volume per site was derived as the median value across all participants, per participant's average actual volume infused, by site: actual volume infused / number of sites. Number of participants with local infusion reactions as a function of each of the categories are presented below.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=30 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants With Local Infusion Reactions, as a Function of Dosing Interval, Infusion Rate Per Site, and Infusion Volume Per Site
3 Week Dosing Interval
8 Participants
Number of Participants With Local Infusion Reactions, as a Function of Dosing Interval, Infusion Rate Per Site, and Infusion Volume Per Site
4 Week Dosing Interval
22 Participants
Number of Participants With Local Infusion Reactions, as a Function of Dosing Interval, Infusion Rate Per Site, and Infusion Volume Per Site
< Median Infusion Rate per Site
15 Participants
Number of Participants With Local Infusion Reactions, as a Function of Dosing Interval, Infusion Rate Per Site, and Infusion Volume Per Site
≥ Median Infusion Rate per Site
15 Participants
Number of Participants With Local Infusion Reactions, as a Function of Dosing Interval, Infusion Rate Per Site, and Infusion Volume Per Site
< Median Infusion Volume per Site
15 Participants
Number of Participants With Local Infusion Reactions, as a Function of Dosing Interval, Infusion Rate Per Site, and Infusion Volume Per Site
≥ Median Infusion Volume per Site
15 Participants

PRIMARY outcome

Timeframe: Baseline, up to 6.6 years

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

Number of participants whose anti-hyaluronidase antibody titers rose by ≥4 fold from the baseline value at any point during the study was assessed.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants Whose Anti-Hyaluronidase Binding Antibody Titers Rose by ≥4-fold From Baseline
16 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication. Overall number analyzed is the number of participants with data available for analyses.

Binding antibodies were defined as anti-rHuPH20 titer ≥1:160.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=84 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants With Binding Antibodies to rHuPH20
14 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication. Overall number analyzed is the number of participants with data available for analyses.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=84 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants With Neutralizing Antibodies Binding to rHuPH20
2 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=85 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants With a Decline of Anti-rHuPH20 Binding Antibody Titers to the Antibody Titer Level at Baseline in Study 161403 or to <1:160 Antibody Titer Level at the Study Completion or Early Discontinuation
12 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication. Overall number analyzed is the number of participants who had \>1:10,000 anti-rHuPH20 antibody titers.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=8 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants Who Had >1:10,000 Anti-rHuPH20 Binding Antibody Titers With Neutralizing Antibodies
2 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to end of study (up to 6.6 years)

Population: Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication. Overall number analyzed is the number of participants who had \>1:10,000 anti-rHuPH20 antibody titers.

Outcome measures

Outcome measures
Measure
HYQVIA/HyQvia
n=8 Participants
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
HYQVIA/HyQvia Then HYQVIA/HyQvia
Participants received HYQVIA/HyQvia in the study 161403 and received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Number of Participants Who Had >1:10,000 Anti-rHuPH20 Binding Antibody Titers Showing Cross Reactivity With Hyaluronidase (Hyal)-1,2 and 4
0 Participants

Adverse Events

HYQVIA/HyQvia

Serious events: 20 serious events
Other events: 63 other events
Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure
HYQVIA/HyQvia
n=85 participants at risk
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Gastrointestinal disorders
Abdominal pain
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
Appendicitis
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
COVID-19
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Cardiac disorders
Cardiac failure
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholangiocarcinoma
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Nervous system disorders
Conus medullaris syndrome
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Psychiatric disorders
Depression
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Gastrointestinal disorders
Diarrhoea
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders
Fibromyalgia
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders
Hypoventilation
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Gastrointestinal disorders
Inguinal hernia
2.4%
2/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Nervous system disorders
Ischaemic stroke
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Mantle cell lymphoma
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Eye disorders
Papilloedema
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
Pulmonary tuberculoma
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
Pulmonary tuberculosis
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Cardiac disorders
Sinus tachycardia
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
Skin infection
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Nervous system disorders
Syncope
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders
Systemic lupus erythematosus
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
Tuberculosis
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
Urinary tract infection
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Reproductive system and breast disorders
Vaginal polyp
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Cardiac disorders
Ventricular fibrillation
1.2%
1/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

Other adverse events

Other adverse events
Measure
HYQVIA/HyQvia
n=85 participants at risk
Participants received HYQVIA/HyQvia (rHuPH20 at a dose of 80 U/g IgG, followed by SC IGI 10%) at the same monthly equivalent dose as the individual participant's IgG treatment in Study 161403, every 3 or 4 weeks in this Extension Study for 77.3 months or until relapse.
Gastrointestinal disorders
Abdominal pain
8.2%
7/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders
Arthralgia
14.1%
12/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders
Back pain
7.1%
6/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
COVID-19
21.2%
18/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Gastrointestinal disorders
Diarrhoea
12.9%
11/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Skin and subcutaneous tissue disorders
Erythema
5.9%
5/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Injury, poisoning and procedural complications
Fall
5.9%
5/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
General disorders
Fatigue
14.1%
12/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Nervous system disorders
Headache
27.1%
23/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Vascular disorders
Hypertension
9.4%
8/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
Influenza
9.4%
8/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
General disorders
Infusion site erythema
15.3%
13/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
General disorders
Infusion site pain
5.9%
5/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
General disorders
Infusion site pruritus
5.9%
5/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders
Myalgia
5.9%
5/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Gastrointestinal disorders
Nausea
12.9%
11/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
5.9%
5/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders
Pain in extremity
7.1%
6/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
General disorders
Pyrexia
20.0%
17/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
Upper respiratory tract infection
8.2%
7/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Infections and infestations
Urinary tract infection
8.2%
7/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.
Gastrointestinal disorders
Vomiting
9.4%
8/85 • From the first dose of study drug up to end of study (up to 6.6 years)
Safety Analysis Set included all participants who were enrolled in this Extension Study and who received at least one dose of study medication.

Additional Information

Study Director

Takeda

Phone: +1-877-825-3327

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place