HYQVIA

The rate of ASBI was defined as the mean number of ASBI per participant-year based on the United States (U.S.) Food and drugs Administration (FDA) guidance for industry to support marketing of human immune globulin intravenous (IGIV) as replacement therapy for primary humoral immunodeficiency and the European Medicines Agency (EMA) guideline on the clinical investigation of human normal immunoglobulin for SC and /or intramuscular administration. ASBI included bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess, diagnosed according to the Diagnostic Criteria for Acute Serious Bacterial Infections.

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.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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).

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.

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.

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).

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.

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.

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.

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.

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.

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 antibody titers rose by ≥4 fold from the baseline value at any point during the study was assessed.

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

Relapse rate is defined as the percentage of participants who experience a worsening of functional disability. Worsening of functional disability defined as an increase of \>=1 point relative to the pre- subcutaneous (SC) treatment baseline score in 2 consecutive adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. The INCAT disability score is an effective and responsive tool to assess clinical response to treatment in CIDP. The disability score ranges from 0 to 10 points, where 0 is normal (eg, no upper limb problems and walking not affected) and 10 is severely incapacitated (eg, inability to move either arm for any purposeful movement and restricted to wheelchair, unable to stand and walk a few steps with help).

Responder rate is defined as clinically meaningful improvement in functional ability defined as a decrease of \>=1 point in the adjusted INCAT disability score at the completion of the intravenous (IV) treatment period \[6 months\] or at the last study visit of the IV treatment period, relative to the pre-IV treatment baseline score.

A tolerability event was considered to have occurred if an infusion was tolerable. An infusion was considered tolerable if the infusion rate was not reduced, or the infusion was not interrupted or stopped, due to an adverse event (AE) related to HYQVIA infusion. Tolerability was measured in terms of the number of participants for which the infusions was tolerable. Number of participants who tolerated all initiated HYQVIA Infusion were reported.