Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Conditions
Brief summary
Adults with Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) who have completed study 161403 will be able to take part in this study. The main aim of the study is to evaluate side effects in the long-term treatment with HYQVIA/HyQvia. All participants will receive HYQVIA/HyQvia in the same way as they were receiving in study 161403. The dosing interval of HYQVIA/HyQvia can be adjusted after 12 weeks of treatment in study 161505 if the study doctor determines that it is safe to do so. Participants will visit the clinic within 1 week after the first and second dose of HYQVIA/HyQvia and then every 12 weeks for the duration of the study.
Interventions
BIOLOGICALHYQVIA
Participants received HYQVIA/HyQvia SC which contains both Immune Globulin Infusion 10% (Human) (IGI, 10%) and recombinant human hyaluronidase (rHuPH20).
Sponsors
Takeda Development Center Americas, Inc.
Baxalta now part of Shire
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has completed Epoch 1 of Study 161403 without CIDP worsening. 2. If female of childbearing potential, the participant must have a negative pregnancy test at baseline and agree to employ adequate birth control measures (eg, birth control pills/patches, intrauterine device, or diaphragm or condom \[for male partner\] with spermicidal jelly or foam) throughout the course of the study.
Exclusion criteria
1. Participant has a serious medical condition such that the participant's safety or medical care would be impacted by participation in this Extension Study. 2. New medical condition that developed during participation in study 161403 that, in the judgment of the investigator, could increase risk to the participant or interfere with the evaluation of investigational medicinal product (IMP) and/or conduct of the study. 3. Participant is scheduled to participate in another non-Baxalta clinical study involving an IP or investigational device during the course of this study. 4. The participant is nursing or intends to begin nursing during the course of the study 5. Participant has participated in another clinical study involving an investigational product (IP) or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study (with the exception of study 161403) involving an IP or investigational device during the course of this study. 6. The participant is a family member or employee of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had >1:10,000 Anti-rHuPH20 Binding Antibody Titers With Neutralizing Antibodies | From the first dose of study drug up to end of study (up to 6.6 years) | — |
| Number of Participants With Any Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs), Regardless of Causality | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Participants With Causally Related Treatment-emergent SAEs and AEs | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Participants With Adverse Reactions (ARs) or Suspected Adverse Reactions (SARs) Categorized as Serious and Non-serious | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Percentage of Participants With Treatment-Emergent Adverse Events That May be a Result of Immune-Mediated Responses | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Treatment-Emergent SAEs and AEs Associated With Infusions, Regardless of Causality | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Causally Related Treatment-Emergent SAEs and AEs Associated With Infusions | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of TEAEs Temporally Associated With Infusions | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Serious and Non-Serious ARs or SARs Associated With Infusions | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Infusions Associated With One or More Systemic TEAEs | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Infusions Associated With One or More Local TEAEs | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Intolerability and/or TEAEs | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Infusion | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Participant | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year | From the first dose of study drug up to end of study (up to 6.6 years) | 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). |
| Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Infusion | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Participant | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per 1000 Participant-year | From the first dose of study drug up to end of study (up to 6.6 years) | 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). |
| Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Infusion | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Participant | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per 1000 Participant-year | From the first dose of study drug up to end of study (up to 6.6 years) | 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). |
| Number of Participants With a TEAE That Led to Discontinuation From Study | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Participants With Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Rate of Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses, Expressed as Number of Events Per 100 Infusions | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Participants That Experienced Treatment-Emergent Local Infusion Site Reactions | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Participants With Treatment-Emergent Local Tolerability Events During Ramp-up | During the ramp-up (8 weeks) | 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. |
| Number of Participants With Local Infusion Reactions, as a Function of Dosing Interval, Infusion Rate Per Site, and Infusion Volume Per Site | From the first dose of study drug up to end of study (up to 6.6 years) | 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. |
| Number of Participants Whose Anti-Hyaluronidase Binding Antibody Titers Rose by ≥4-fold From Baseline | Baseline, up to 6.6 years | Number of participants whose anti-hyaluronidase antibody titers rose by ≥4 fold from the baseline value at any point during the study was assessed. |
| Number of Participants With Binding Antibodies to rHuPH20 | From the first dose of study drug up to end of study (up to 6.6 years) | Binding antibodies were defined as anti-rHuPH20 titer ≥1:160. |
| Number of Participants With Neutralizing Antibodies Binding to rHuPH20 | From the first dose of study drug up to end of study (up to 6.6 years) | — |
| 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 | From the first dose of study drug up to end of study (up to 6.6 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants Who Had >1:10,000 Anti-rHuPH20 Binding Antibody Titers Showing Cross Reactivity With Hyaluronidase (Hyal)-1,2 and 4 | From the first dose of study drug up to end of study (up to 6.6 years) |
Countries
Argentina, Brazil, Canada, Colombia, Czechia, Denmark, France, Germany, Greece, Italy, Mexico, Poland, Serbia, Slovakia, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 39 investigative sites worldwide from 14 November 2016 to 04 July 2023.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| HYQVIA/HyQvia 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. | 85 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 1 |
| Overall Study | Physician Decision | 21 |
| Overall Study | Reason Not Specified | 5 |
| Overall Study | Site Terminated by Sponsor | 35 |
| Overall Study | Withdrawal by Subject | 19 |
Baseline characteristics
| Characteristic | HYQVIA/HyQvia |
|---|---|
| Age, Continuous | 54.3 years STANDARD_DEVIATION 13.11 |
| Body Mass Index (BMI) | 27.42 kilograms per meter square (kg/m^2) STANDARD_DEVIATION 5.587 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Height | 171.5 centimeters (cm) STANDARD_DEVIATION 10.98 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 81 Participants |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 46 Participants |
| Weight | 80.89 kilograms (kg) STANDARD_DEVIATION 18.856 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 85 |
| other Total, other adverse events | 63 / 85 |
| serious Total, serious adverse events | 20 / 85 |
Outcome results
Primary
Number of Causally Related Treatment-Emergent SAEs and AEs Associated With Infusions
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | Number of Causally Related Treatment-Emergent SAEs and AEs Associated With Infusions | IP-Related Serious TEAEs | 3 events in participants |
| HYQVIA/HyQvia | Number of Causally Related Treatment-Emergent SAEs and AEs Associated With Infusions | IP-Related TEAEs | 798 events in participants |
Primary
Number of Infusions Associated With One or More Local TEAEs
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HYQVIA/HyQvia | Number of Infusions Associated With One or More Local TEAEs | 17 infusions |
Primary
Number of Infusions Associated With One or More Systemic TEAEs
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HYQVIA/HyQvia | Number of Infusions Associated With One or More Systemic TEAEs | 50 infusions |
Primary
Number of Infusions for Which the Infusion Rate Was Reduced and/or the Infusion Was Interrupted or Stopped Due to Intolerability and/or TEAEs
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HYQVIA/HyQvia | 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
Number of Participants That Experienced Treatment-Emergent Local Infusion Site Reactions
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HYQVIA/HyQvia | Number of Participants That Experienced Treatment-Emergent Local Infusion Site Reactions | 30 Participants |
Primary
Number of Participants Who Had >1:10,000 Anti-rHuPH20 Binding Antibody Titers With Neutralizing Antibodies
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HYQVIA/HyQvia | Number of Participants Who Had >1:10,000 Anti-rHuPH20 Binding Antibody Titers With Neutralizing Antibodies | 2 Participants |
Primary
Number of Participants Whose Anti-Hyaluronidase Binding Antibody Titers Rose by ≥4-fold From Baseline
Number of participants whose anti-hyaluronidase antibody titers rose by ≥4 fold from the baseline value at any point during the study was assessed.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HYQVIA/HyQvia | Number of Participants Whose Anti-Hyaluronidase Binding Antibody Titers Rose by ≥4-fold From Baseline | 16 Participants |
Primary
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
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HYQVIA/HyQvia | 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
Number of Participants With Adverse Reactions (ARs) or Suspected Adverse Reactions (SARs) Categorized as Serious and Non-serious
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HYQVIA/HyQvia | Number of Participants With Adverse Reactions (ARs) or Suspected Adverse Reactions (SARs) Categorized as Serious and Non-serious | Any Serious AR/SAR | 7 Participants |
| HYQVIA/HyQvia | 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
Number of Participants With Any Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs), Regardless of Causality
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HYQVIA/HyQvia | Number of Participants With Any Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs), Regardless of Causality | Any TEAE | 76 Participants |
| HYQVIA/HyQvia | Number of Participants With Any Treatment-emergent Serious Adverse Events (SAEs) and Adverse Events (AEs), Regardless of Causality | Any Serious TEAE | 20 Participants |
Primary
Number of Participants With a TEAE That Led to Discontinuation From Study
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HYQVIA/HyQvia | Number of Participants With a TEAE That Led to Discontinuation From Study | 4 Participants |
Primary
Number of Participants With Binding Antibodies to rHuPH20
Binding antibodies were defined as anti-rHuPH20 titer ≥1:160.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HYQVIA/HyQvia | Number of Participants With Binding Antibodies to rHuPH20 | 14 Participants |
Primary
Number of Participants With Causally Related Treatment-emergent SAEs and AEs
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HYQVIA/HyQvia | Number of Participants With Causally Related Treatment-emergent SAEs and AEs | Any IP-Related TEAE | 51 Participants |
| HYQVIA/HyQvia | Number of Participants With Causally Related Treatment-emergent SAEs and AEs | Any IP-Related Serious TEAE | 3 Participants |
Primary
Number of Participants With Local Infusion Reactions, as a Function of Dosing Interval, Infusion Rate Per Site, and Infusion Volume Per Site
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.
Time frame: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HYQVIA/HyQvia | 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 |
| HYQVIA/HyQvia | 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 |
| HYQVIA/HyQvia | 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 |
| HYQVIA/HyQvia | 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 |
| HYQVIA/HyQvia | 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 |
| HYQVIA/HyQvia | 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 |
Primary
Number of Participants With Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HYQVIA/HyQvia | Number of Participants With Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses | 3 Participants |
Primary
Number of Participants With Neutralizing Antibodies Binding to rHuPH20
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HYQVIA/HyQvia | Number of Participants With Neutralizing Antibodies Binding to rHuPH20 | 2 Participants |
Primary
Number of Participants With Treatment-Emergent Local Tolerability Events During Ramp-up
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HYQVIA/HyQvia | Number of Participants With Treatment-Emergent Local Tolerability Events During Ramp-up | 6 Participants |
| HYQVIA/HyQvia Then HYQVIA/HyQvia | Number of Participants With Treatment-Emergent Local Tolerability Events During Ramp-up | 13 Participants |
Primary
Number of Serious and Non-Serious ARs or SARs Associated With Infusions
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | Number of Serious and Non-Serious ARs or SARs Associated With Infusions | Serious ARs/SARs | 8 events in participants |
| HYQVIA/HyQvia | Number of Serious and Non-Serious ARs or SARs Associated With Infusions | Non-Serious ARs/SARs | 913 events in participants |
Primary
Number of TEAEs Temporally Associated With Infusions
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HYQVIA/HyQvia | Number of TEAEs Temporally Associated With Infusions | 857 events in participants |
Primary
Number of Treatment-Emergent SAEs and AEs Associated With Infusions, Regardless of Causality
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | Number of Treatment-Emergent SAEs and AEs Associated With Infusions, Regardless of Causality | Serious TEAEs | 30 events in participants |
| HYQVIA/HyQvia | Number of Treatment-Emergent SAEs and AEs Associated With Infusions, Regardless of Causality | TEAEs | 1406 events in participants |
Primary
Percentage of Participants With Treatment-Emergent Adverse Events That May be a Result of Immune-Mediated Responses
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HYQVIA/HyQvia | Percentage of Participants With Treatment-Emergent Adverse Events That May be a Result of Immune-Mediated Responses | 7.1 percentage of participants |
Primary
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per 1000 Participant-year
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | 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 |
| HYQVIA/HyQvia | 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
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Infusion
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Infusion | Systemic ARs/SARs | 0.11 reactions/infusion |
| HYQVIA/HyQvia | Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Infusion | Local ARs/SARs | 0.15 reactions/infusion |
Primary
Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Participant
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Participant | Systemic ARs/SARs | 4.58 reactions/participant |
| HYQVIA/HyQvia | Rate of ARs or SARs Categorized as Local and Systemic, Expressed as Reactions Per Participant | Local ARs/SARs | 6.16 reactions/participant |
Primary
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per 1000 Participant-year
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | 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 |
| HYQVIA/HyQvia | 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
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Infusion
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | 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 |
| HYQVIA/HyQvia | 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
Rate of IP-Related TEAEs Categorized as Systemic and Local, Expressed as Number of Events Per Participant
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | 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 |
| HYQVIA/HyQvia | 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
Rate of Moderate or Severe TEAEs That May be a Result of Immune-Mediated Responses, Expressed as Number of Events Per 100 Infusions
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HYQVIA/HyQvia | 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
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per 1000 Participant-year
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | 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 |
| HYQVIA/HyQvia | 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
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Infusion
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Infusion | Systemic TEAEs | 0.25 AEs/infusion |
| HYQVIA/HyQvia | 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
Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Participant
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HYQVIA/HyQvia | Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Participant | Systemic TEAEs | 10.38 AEs/participant |
| HYQVIA/HyQvia | Rate of TEAEs Categorized as Systemic and Local Regardless of Causality, Expressed as Number of Events Per Participant | Local TEAEs | 6.16 AEs/participant |
Secondary
Number of Participants Who Had >1:10,000 Anti-rHuPH20 Binding Antibody Titers Showing Cross Reactivity With Hyaluronidase (Hyal)-1,2 and 4
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HYQVIA/HyQvia | 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 |