Primary Immunodeficiency Diseases (PID)
Conditions
Brief summary
The purpose of the study is to acquire additional data on efficacy, safety, tolerability, immunogenicity, pharmacokinetic (PK) and other parameters of HYQVIA in pediatric (age ≥ 2 to \<16 years) participants with primary immunodeficiency disease (PIDD).
Interventions
BIOLOGICALHYQVIA
Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (IGI, 10% with rHuPH20)
Sponsors
Baxalta Innovations GmbH, now part of Shire
Baxalta now part of Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 15 Years
Healthy volunteers
No
Inclusion criteria
1. Participant must have a documented diagnosis of a form of primary immunodeficiency (PI) involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the International Union of Immunological Societies (IUIS) Scientific Committee 2015 (Picard et al., 2015) prior to enrollment. The diagnosis must be confirmed by the sponsor´s Medical Director prior to first treatment with IP in the study. 2. Participant is at least two and below 16 years of age at the time of screening. 3. Participant has been receiving a consistent dose of Immunoglobulin G (IgG), administered in compliance with the respective product information for a period of at least three months prior to screening. The average minimum pre-study dose over that interval was equivalent to 300 mg/kg BW / 4 weeks and a maximum dose equivalent to 1000 mg/kg body weight (BW) / 4 weeks. 4. Participant has a serum trough level of IgG \> 5 g/L at screening. 5. If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study. 6. Participant /legally authorized representative is willing and able to comply with the requirements of the protocol.
Exclusion criteria
1. Participant has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2. 2. Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent): 1. Persistent alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 2.5 times the upper limit of normal (ULN) for the testing laboratory 2. Persistent severe neutropenia (defined as an absolute neutrophil count \[ANC\] ≤ 500/mm\^3) 3. Participant has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site. 4. Participant has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following intravenous (IV) immunoglobulin, subcutaneous (SC) immunoglobulin, and/or Immune Serum Globulin (ISG) infusions. 5. Participant has severe Immunoglobulin A (IgA) deficiency (less than 7.0 mg/dL) with known anti-IgA antibodies and a history of hypersensitivity. 6. Participant has a known allergy to hyaluronidase. 7. Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening. 8. Participant has a bleeding disorder or a platelet count less than 20,000/μL, or who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of SC therapy. 9. Participant has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator. 10. Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study. 11. Participant is a family member or employee of the investigator. 12. If female, participant is pregnant or lactating at the time of enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate Represented as Mean Number of Acute Serious Bacterial Infections (ASBI) Per Participant-year | From first dose of study drug up to end of Study Epoch 2 (up to approximately 37.2 months) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | Study Epoch 2, Year 1: Months 0, 6, and 12; Year 2: Months 18, 24 and 36 | — |
| Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorized as Clostridium Tetani Toxoid and Hepatitis B Virus | Study Epoch 2, Year 2: Months 6, 24, and 36 | — |
| Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen Haemophilus Influenzae B | Study Epoch 2, Year 2: Months 6, 24, and 36 | — |
| Epoch 2: Area Under the Curve Normalized for Week (AUCweek) | Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion | — |
| Epoch 2: Area Under the Curve Over the Infusion Interval (AUCTau) | Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion | — |
| Epoch 2: Apparent Clearance (CL/F) | Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion | — |
| Epoch 2: Maximum Concentration (Cmax) | Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion | — |
| Epoch 2: Minimum Concentration (Cmin) | Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion | — |
| Epoch 2: Time to Maximum Concentration (Tmax) | Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion | — |
| Epoch 2: Terminal Half-life (T 1/2) | Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion | — |
| Number of Participants With Serious Adverse Events (SAEs) Excluding Infections, Related and Not Related | From first dose of study drug up to EOS (up to 4 years 9 months) | An SAE is defined as an untoward medical occurrence that at any dose is fatal, life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event. Number of participants who experienced SAEs, related or not related, was reported. |
| Rate of SAEs Excluding Infections, Related and Not Related, Per Infusion | From first dose of study drug up to EOS (up to 4 years 9 months) | Rate of SAEs per infusion was calculated as number of serious adverse events/total number of infusions administered to participants in the analysis set. Rate of SAEs per infusion (excluding infections) was reported. |
| Number of Participants With Local TEAEs Excluding Infections, Related and Not Related | From first dose of study drug up to EOS (up to 4 years 9 months) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced local TEAEs, related or not related, was reported. |
| Number of Participants With All Treatment Emergent Adverse Events (TEAEs) Excluding Infections, Related and Not Related | From first dose of study drug up to EOS (up to 4 years 9 months) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced TEAEs, related or not related, was reported. |
| Rate of All TEAEs Excluding Infections, Related and Not Related, Per Infusion | From first dose of study drug up to EOS (up to 4 years 9 months) | Rate of all TEAEs per infusion was calculated as number of any adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of any adverse reactions per infusion (excluding infections) was reported. |
| Rate of Local TEAEs Excluding Infections, Related and Not Related, Per Infusion | From first dose of study drug up to EOS (up to 4 years 9 months) | Rate of local TEAEs per infusion was calculated as number of local TEAEs/total number of infusions administered to participants in the analysis set. Rate of local TEAEs per infusion (excluding infections) was reported. |
| Number of Participants With Systemic TEAEs Excluding Infections, Related and Not Related | From first dose of study drug up to EOS (up to 4 years 9 months) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced systemic TEAEs, related or not related, was reported. |
| Rate of Systemic TEAEs Excluding Infections, Related and Not Related, Per Infusion | From first dose of study drug up to EOS (up to 4 years 9 months) | Rate of systemic TEAEs per infusion was calculated as number of systemic TEAEs/total number of infusions administered to participants in the analysis set. Rate of systemic TEAEs per infusion (excluding infections) was reported. |
| Number of Participants With All Temporally Associated TEAEs Excluding Infections | From beginning of infusion up to 72 hours post infusion | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced all temporally associated TEAEs, related or not related, was reported. |
| Rate of All Temporally Associated TEAEs Excluding Infections Per Infusion | From beginning of infusion up to 72 hours post infusion | Rate of all temporally associated TEAEs per infusion was calculated as number of all temporally associated TEAEs/total number of infusions administered to participants in the analysis set. Rate of all temporally associated TEAEs per infusion (excluding infections) was reported. |
| Number of Participants With All Related (Causally) and/or Temporally Associated TEAEs Excluding Infections | From beginning of infusion up to 72 hours post infusion | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants with any related (causally) and/or temporally associated TEAEs (excluding infections) was reported. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. |
| Rate of Participants With All Related (Causally) and/or Temporally Associated TEAEs Excluding Infections Per Infusion | From beginning of infusion up to 72 hours post infusion | Rate of any related (causally) and/or temporally associated TEAEs per infusion was calculated as number of related and/or temporally associated adverse events/ total number of infusions administered to participants in the analysis set. TEAEs recorded in the study database as possibly related or probably related to HYQVIA are considered HYQVIA-related adverse events. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Rate of any related (causally) and/or temporally associated TEAEs per infusion (excluding infections) was reported. |
| Percentage of Participants With Any TEAEs Excluding Infections | From first dose of study drug up to EOS (up to 4 years 9 months) | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Percentages are rounded off to whole number at the nearest decimal. |
| Number of Participants Who Developed Positive Titer (≥160) of Binding or Neutralizing Antibodies to rHuPH20 | From first dose of study drug up to EOS (up to 4 years 9 months) | Number of participants who developed positive titer (rHuPH20 titer ≥160) of binding antibodies to rHuPH20 was reported. Neutralizing antibodies were only tested if the participant had a titer of ≥160 of binding antibodies. Participants with multiple assessments of titer of ≥160 of binding antibodies are counted only once. |
| Percentage of Participants Who Developed Positive Titer (≥160) of Binding or Neutralizing Antibodies to rHuPH20 | From first dose of study drug up to EOS (up to 4 years 9 months) | Percentage of participants who developed positive titer (rHuPH20 titer ≥160) of binding antibodies to rHuPH20 was reported. Neutralizing antibodies were only tested if the participant had a titer of ≥160 of binding antibodies. Participants with multiple assessments of titer of ≥160 of binding antibodies are counted only once. Percentages are rounded off to whole number at the nearest decimal. |
| Epoch 2: Number of Infusions Per Month | Study Epoch 2: Up to 36 months | — |
| Epoch 2: Number of Infusion Sites (Needle Sticks) Per Infusion | Study Epoch 2: Up to 36 months | — |
| Epoch 2: Number of Infusion Sites (Needle Sticks) Per Month | Study Epoch 2: Up to 36 months | — |
| Epoch 2: Duration of Infusion | Study Epoch 2: Up to 36 months | Duration of infusion is calculated as (stop time of infusion - start time of infusion) (in Epoch 2). Duration of infusion is the time from the start of rHuPH20 infusion until the stop time of immunoglobulin infusion. |
| Epoch 2: Maximum Infusion Rate Per Site | Study Epoch 2: Up to 36 months | HYQVIA treatment infusions in Epoch 2 were given at a rate of 10 milliliters per hour per site (mL/h/site) to 160 ml/h/site (body weight \[BW\] of \<40 kg) and 10 mL/h/site to 300 mL/h/site (BW of ≥40 kg). |
| Epoch 2: Infusion Volume Per Site | Study Epoch 2: Up to 36 months | Infusion volume per site is calculated as (actual IgG volume (mL) / total number of infusion sites used). |
| Epoch 2: Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE | Study Epoch 2: Up to 36 months | — |
| Epoch 2: Percentage of Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE | Study Epoch 2: Up to 36 months | Percentages are rounded off to whole number at the nearest decimal. |
| Epoch 1: Number of Weeks to Reach Final Dose Interval | Epoch 1 (up to 6 weeks) | — |
| Epoch 2: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 | Study Epoch 2: Up to 36 months | Percentages are rounded off to whole number at the nearest decimal. Percentages may sum up to more than 100% as assigned treatment interval could be changed during the study. |
| Epoch 2: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 for 12 Months | Study Epoch 2: Up to 12 months | Percentages are rounded off to whole number at the nearest decimal. |
| Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36 | Peds-QL=generic questionnaire developed and validated to measure HRQoL among pediatric population. It included assessment of 4 dimensions: physical functioning (8 items), emotional functioning (8 items), social functioning (8 items), and school functioning (Age groups: Toddler (2-4years),Young child (5-7years),Child (8-12years), and Teens (13-\<16years). Depending on the participants age, questionnaire may be completed by participant or parent/caregiver as appropriate. Items were scored on a 5-point Likert scale: 0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; and 4=almost always a problem). All Scores were transformed on a total scale from 0-100 where, 0=100, 1=75, 2=50, 3=25, and 4=0. Higher scores indicating better health status. End of Epoch 2 summarizes all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1). |
| HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36 | The EQ-5D is a validated, self-administered assessment of overall health consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Participants were asked to describe their health state that day by choosing 1 of 3 responses that reflect the levels of severity for each of the five dimensions: no problems, some or moderate problems, or extreme problems. The domain scores are calculated with higher scores indicating worsening health status. The EQ-5D also includes a standard vertical 20-cm visual analogue scale (similar to a thermometer) for recording a participant's rating of their current HRQoL state, which ranged from 0 to 100, where 0 indicated worst imaginable health state and 100 was best imaginable health state. End of Epoch 2 summarizes all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1). |
| Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36 | The LQI is a validated questionnaire assessing participant perceptions of their HRQoL and their treatment specifically among participants who use IgG therapy. This questionnaire covers 4 domains: treatment interferences, therapy-related problems, therapy setting, and treatment costs. The LQI domains are scored from 0 to 100, with higher scores associated with better IgG treatment satisfaction. End of Epoch 2 summarizes all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1). |
| Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36 | The TSQM-9 is a 9-item, validated, self-administered instrument to assess participant satisfaction with medication, which assesses 3 domains: effectiveness, convenience, and global satisfaction. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction. End of Epoch 2 summarizes all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1). |
| Rate Represented as Mean Number of All Infections Per Participant-year | From first dose of study drug up to end of Study Epoch 2 (up to approximately 37.2 months) | The rate of all infections was defined as the mean number of all infections per participant-year. Number of all infections was calculated as number of infections per participant-year. |
| Health Resource Utilization: Days Not Able to go to School or Work, or to Perform Normal Daily Activities | From first dose of study drug up to EOS (up to 4 years 9 months) | Days not able to go to school or work, or to perform normal daily activities due to infection or other illnesses were calculated as days not able to go to school or work, or to perform normal daily activities due to infection or other illnesses per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all participants in the analysis set, divided by 365.25. |
| Health Resource Utilization: Days on Antibiotics | From first dose of study drug up to EOS (up to 4 years 9 months) | Days on antibiotics were calculated as days on antibiotics per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all participants in the analysis set, divided by 365.25. |
| Health Resource Utilization: Number of Hospitalizations | From first dose of study drug up to EOS (up to 4 years 9 months) | Number of hospitalizations, indication for the hospitalization (infection or non-infection) were calculated as number of hospitalizations, indication for the hospitalization (infection or non-infection) per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all participants in the analysis set, divided by 365.25. |
| Health Resource Utilization: Number of Days Hospitalized Per Participant-Year | From first dose of study drug up to EOS (up to 4 years 9 months) | Number of days hospitalized were calculated as number of days hospitalized per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all participants in the analysis set, divided by 365.25. |
| Treatment Preference and Satisfaction: Number of Participants Who Completed Treatment Preference Questionnaire | Study Epoch 2: Up to Month 36 | The treatment preference questionnaire, internally developed by the study sponsor, is a self-administered, non-validated scale assessing participant preference for various attributes of immunoglobulin G (IgG) therapy.End of Epoch 2 summarizes all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1). |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 19 investigative sites in the United States from 25 September 2017 to 20 July 2022. Pediatric participants with a diagnosis of primary immunodeficiency diseases (PIDD) were enrolled in this study.
Pre-assignment details
Pediatric participants who received intravenous(IV) or non-HYQVIA subcutaneous(SC) immunoglobulin therapy prior to enrollment received ramp-up doses of HYQVIA in Epoch 1 and at 3- or 4-week intervals in Epoch 2. Epoch 3 was planned for safety follow-up if needed, however no participants continued in Epoch 3. Data is reported only for Epoch 1 and 2.
Participants by arm
| Arm | Count |
|---|---|
| Epoch 1 Pediatric participants with PIDD who were on IV or non-HYQVIA SC treatment with immunoglobulin were enrolled and treated with HYQVIA SC with a dose or interval ramp-up period of up to six weeks. HYQVIA dose was planned to be equivalent to 100% (± 5%) of pre-study treatment. Dose frequency was one treatment interval of one week, then one treatment interval of two weeks for participants who were planned to be treated every three weeks, and one more treatment interval of three weeks for participants who were planned to be treated every four weeks. | 44 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Epoch 1 (Six-week Ramp-up Period) | Adverse Event | 1 | 0 |
| Epoch 2 (36 Months After Epoch 1) | Adverse Event | 0 | 1 |
| Epoch 2 (36 Months After Epoch 1) | Physician Decision | 0 | 1 |
| Epoch 2 (36 Months After Epoch 1) | Reason not Specified | 0 | 1 |
| Epoch 2 (36 Months After Epoch 1) | Withdrawal by Subject | 0 | 6 |
Baseline characteristics
| Characteristic | Epoch 1 |
|---|---|
| Age, Continuous | 9.0 years STANDARD_DEVIATION 3.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 133.60 cm STANDARD_DEVIATION 24.024 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 40 Participants |
| Region of Enrollment United States | 44 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 26 Participants |
| Weight | 37.78 kg STANDARD_DEVIATION 19.858 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 44 | 0 / 43 |
| other Total, other adverse events | 28 / 44 | 40 / 43 |
| serious Total, serious adverse events | 1 / 44 | 3 / 43 |
Outcome results
Primary
Rate Represented as Mean Number of Acute Serious Bacterial Infections (ASBI) Per Participant-year
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.
Time frame: From first dose of study drug up to end of Study Epoch 2 (up to approximately 37.2 months)
Population: FAS included all participants who provided informed consent, and met enrollment eligibility.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Rate Represented as Mean Number of Acute Serious Bacterial Infections (ASBI) Per Participant-year | 0.04 ASBI per participant-year | Standard Error 0.027 |
Secondary
Epoch 1: Number of Weeks to Reach Final Dose Interval
Time frame: Epoch 1 (up to 6 weeks)
Population: SAS included all participants who received at least one dose of HyQvia. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 1: Number of Weeks to Reach Final Dose Interval | 6.14 weeks |
Secondary
Epoch 2: Apparent Clearance (CL/F)
Time frame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
Population: PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Apparent Clearance (CL/F) | 56.45 milliliters per day (mL/day) | Geometric Coefficient of Variation 61.4 |
Secondary
Epoch 2: Area Under the Curve Normalized for Week (AUCweek)
Time frame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
Population: Pharmacokinetic analysis set (PKAS) included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in statistical analysis plan (SAP), this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Area Under the Curve Normalized for Week (AUCweek) | 74.57 grams*day per liter (g*day/L) | Geometric Coefficient of Variation 19.4 |
Secondary
Epoch 2: Area Under the Curve Over the Infusion Interval (AUCTau)
Time frame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
Population: PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Area Under the Curve Over the Infusion Interval (AUCTau) | 288.8 g*day/L | Geometric Coefficient of Variation 21.7 |
Secondary
Epoch 2: Duration of Infusion
Duration of infusion is calculated as (stop time of infusion - start time of infusion) (in Epoch 2). Duration of infusion is the time from the start of rHuPH20 infusion until the stop time of immunoglobulin infusion.
Time frame: Study Epoch 2: Up to 36 months
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Duration of Infusion | 85.0 minutes (mins) |
Secondary
Epoch 2: Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE
Time frame: Study Epoch 2: Up to 36 months
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE | Infusions That Were Discontinued | 0 infusions |
| Epoch 1 + Epoch 2 | Epoch 2: Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE | Infusions That Were Slowed | 0 infusions |
| Epoch 1 + Epoch 2 | Epoch 2: Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE | Infusions That Were Interrupted | 17 infusions |
Secondary
Epoch 2: Infusion Volume Per Site
Infusion volume per site is calculated as (actual IgG volume (mL) / total number of infusion sites used).
Time frame: Study Epoch 2: Up to 36 months
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Infusion Volume Per Site | 101.3 mL/site | Standard Deviation 51.69 |
Secondary
Epoch 2: Maximum Concentration (Cmax)
Time frame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
Population: PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Maximum Concentration (Cmax) | 12.94 g/L | Geometric Coefficient of Variation 17.4 |
Secondary
Epoch 2: Maximum Infusion Rate Per Site
HYQVIA treatment infusions in Epoch 2 were given at a rate of 10 milliliters per hour per site (mL/h/site) to 160 ml/h/site (body weight \[BW\] of \<40 kg) and 10 mL/h/site to 300 mL/h/site (BW of ≥40 kg).
Time frame: Study Epoch 2: Up to 36 months
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Maximum Infusion Rate Per Site | 173.5 milliliters per hour per site(mL/h/site) | Standard Deviation 81.32 |
Secondary
Epoch 2: Minimum Concentration (Cmin)
Time frame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
Population: PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Minimum Concentration (Cmin) | 8.571 g/L | Geometric Coefficient of Variation 25.6 |
Secondary
Epoch 2: Number of Infusion Sites (Needle Sticks) Per Infusion
Time frame: Study Epoch 2: Up to 36 months
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Number of Infusion Sites (Needle Sticks) Per Infusion | 1.83 infusion sites per infusion | Standard Deviation 0.366 |
Secondary
Epoch 2: Number of Infusion Sites (Needle Sticks) Per Month
Time frame: Study Epoch 2: Up to 36 months
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Number of Infusion Sites (Needle Sticks) Per Month | 2.17 infusion sites per month |
Secondary
Epoch 2: Number of Infusions Per Month
Time frame: Study Epoch 2: Up to 36 months
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Number of Infusions Per Month | 1.10 infusions per month |
Secondary
Epoch 2: Percentage of Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE
Percentages are rounded off to whole number at the nearest decimal.
Time frame: Study Epoch 2: Up to 36 months
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Percentage of Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE | Infusions That Were Discontinued | 0 percentage of infusions |
| Epoch 1 + Epoch 2 | Epoch 2: Percentage of Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE | Infusions That Were Slowed | 0 percentage of infusions |
| Epoch 1 + Epoch 2 | Epoch 2: Percentage of Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE | Infusions That Were Interrupted | 2.69 percentage of infusions |
Secondary
Epoch 2: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2
Percentages are rounded off to whole number at the nearest decimal. Percentages may sum up to more than 100% as assigned treatment interval could be changed during the study.
Time frame: Study Epoch 2: Up to 36 months
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 | Every 3 Weeks | 18.6 percentage of participants |
| Epoch 1 + Epoch 2 | Epoch 2: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 | Every 4 Weeks | 83.7 percentage of participants |
Secondary
Epoch 2: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 for 12 Months
Percentages are rounded off to whole number at the nearest decimal.
Time frame: Study Epoch 2: Up to 12 months
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 for 12 Months | 74.4 percentage of participants |
Secondary
Epoch 2: Terminal Half-life (T 1/2)
Time frame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
Population: PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Terminal Half-life (T 1/2) | 44.98 days | Geometric Coefficient of Variation 45.9 |
Secondary
Epoch 2: Time to Maximum Concentration (Tmax)
Time frame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
Population: PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Overall number analyzed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Time to Maximum Concentration (Tmax) | 4.20 days |
Secondary
Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses
Time frame: Study Epoch 2, Year 1: Months 0, 6, and 12; Year 2: Months 18, 24 and 36
Population: FAS=all participants who provided informed consent, and met enrollment eligibility. Only FAS participants in Epoch 2 were analyzed for this outcome measure. Overall number analyzed=number of participants with data available for analyses. Number analyzed=number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 2: Month 6 | 3.156 grams per liter (g/L) | Standard Deviation 0.6694 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Total: Month 0 | 10.381 grams per liter (g/L) | Standard Deviation 2.9191 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Total: Month 6 | 9.199 grams per liter (g/L) | Standard Deviation 1.9577 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Total: Month 12 | 9.214 grams per liter (g/L) | Standard Deviation 1.98 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Total: Month 18 | 13.80 grams per liter (g/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Total: Month 24 | 10.80 grams per liter (g/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Total: Month 36 | 13.50 grams per liter (g/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 1: Month 0 | 5.888 grams per liter (g/L) | Standard Deviation 2.7193 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 1: Month 6 | 5.317 grams per liter (g/L) | Standard Deviation 1.4887 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 1: Month 12 | 5.284 grams per liter (g/L) | Standard Deviation 1.2103 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 1: Month 18 | 7.590 grams per liter (g/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 1: Month 24 | 7.710 grams per liter (g/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 2: Month 0 | 3.311 grams per liter (g/L) | Standard Deviation 0.6833 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 2: Month 12 | 3.106 grams per liter (g/L) | Standard Deviation 0.5839 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 2: Month 18 | 3.480 grams per liter (g/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 2: Month 24 | 3.510 grams per liter (g/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 3: Month 0 | 0.534 grams per liter (g/L) | Standard Deviation 0.2838 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 3: Month 6 | 0.508 grams per liter (g/L) | Standard Deviation 0.2545 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 3: Month 12 | 0.507 grams per liter (g/L) | Standard Deviation 0.2799 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 3: Month 18 | 0.360 grams per liter (g/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 3: Month 24 | 0.430 grams per liter (g/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 4: Month 0 | 0.2998 grams per liter (g/L) | Standard Deviation 0.26802 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 4: Month 6 | 0.3161 grams per liter (g/L) | Standard Deviation 0.32899 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 4: Month 12 | 0.3118 grams per liter (g/L) | Standard Deviation 0.3279 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 4: Month 18 | 0.9380 grams per liter (g/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | IgG Subclass 4: Month 24 | 1.4560 grams per liter (g/L) | — |
Secondary
Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen Haemophilus Influenzae B
Time frame: Study Epoch 2, Year 2: Months 6, 24, and 36
Population: FAS=all participants who provided informed consent, and met enrollment eligibility. Only FAS participants in Epoch 2 were analyzed for this outcome measure. Overall number analyzed=number of participants with data available for analyses. Number analyzed=number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen Haemophilus Influenzae B | Month 6 | 1.839 milligrams per liter (mg/L) | Standard Deviation 1.5222 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen Haemophilus Influenzae B | Month 24 | 1.810 milligrams per liter (mg/L) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen Haemophilus Influenzae B | Completion/Termination (Month 36) | 1.678 milligrams per liter (mg/L) | Standard Deviation 0.8009 |
Secondary
Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorized as Clostridium Tetani Toxoid and Hepatitis B Virus
Time frame: Study Epoch 2, Year 2: Months 6, 24, and 36
Population: FAS=all participants who provided informed consent, and met enrollment eligibility. Only FAS participants in Epoch 2 were analyzed for this outcome measure. Overall number analyzed=number of participants with data available for analyses. Number analyzed=number of participants with data available for analysis at specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorized as Clostridium Tetani Toxoid and Hepatitis B Virus | Clostridium Tetani Toxoid Antibody: Month 6 | 1.685 international unit per milliliter(IU/mL) | Standard Deviation 0.6793 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorized as Clostridium Tetani Toxoid and Hepatitis B Virus | Clostridium Tetani Toxoid Antibody: Month 24 | 2.450 international unit per milliliter(IU/mL) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorized as Clostridium Tetani Toxoid and Hepatitis B Virus | Clostridium Tetani Toxoid Antibody: Completion/ Termination (Month 36) | 1.598 international unit per milliliter(IU/mL) | Standard Deviation 0.5889 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorized as Clostridium Tetani Toxoid and Hepatitis B Virus | Hepatitis B Virus Antibody: Month 6 | 199.6 international unit per milliliter(IU/mL) | Standard Deviation 122.97 |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorized as Clostridium Tetani Toxoid and Hepatitis B Virus | Hepatitis B Virus Antibody: Month 24 | 146.0 international unit per milliliter(IU/mL) | — |
| Epoch 1 + Epoch 2 | Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorized as Clostridium Tetani Toxoid and Hepatitis B Virus | Hepatitis B Virus Antibody: Completion/ Termination (Month 36) | 256.7 international unit per milliliter(IU/mL) | Standard Deviation 219.53 |
Secondary
Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score
Peds-QL=generic questionnaire developed and validated to measure HRQoL among pediatric population. It included assessment of 4 dimensions: physical functioning (8 items), emotional functioning (8 items), social functioning (8 items), and school functioning (Age groups: Toddler (2-4years),Young child (5-7years),Child (8-12years), and Teens (13-\<16years). Depending on the participants age, questionnaire may be completed by participant or parent/caregiver as appropriate. Items were scored on a 5-point Likert scale: 0=never a problem; 1=almost never a problem; 2=sometimes a problem; 3=often a problem; and 4=almost always a problem). All Scores were transformed on a total scale from 0-100 where, 0=100, 1=75, 2=50, 3=25, and 4=0. Higher scores indicating better health status. End of Epoch 2 summarizes all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1).
Time frame: Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
Population: SAS included all participants who received at least one dose of HyQvia. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Baseline: 2-4 years | 72.67 score on a scale | Standard Deviation 12.969 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Baseline: 5-7 years | 77.29 score on a scale | Standard Deviation 18.908 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Baseline: 8-12 years | 75.42 score on a scale | Standard Deviation 17.227 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Baseline: 13-<16 years | 76.09 score on a scale | Standard Deviation 7.894 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at Epoch 2 Month 12: 2-4 years | 4.57 score on a scale | Standard Deviation 17.134 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at Epoch 2 Month 12: 5-7 years | -3.74 score on a scale | Standard Deviation 15.17 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at Epoch 2 Month 12: 8-12 years | 0.84 score on a scale | Standard Deviation 21.05 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at Epoch 2 Month 12: 13-<16 years | -6.09 score on a scale | Standard Deviation 8.75 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at Completion/ termination (Month 36): 2-4 years | 8.73 score on a scale | Standard Deviation 18.799 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at Completion/ termination (Month 36): 5-7 years | -26.09 score on a scale | — |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at Completion/ termination (Month 36): 8-12 years | -5.16 score on a scale | Standard Deviation 19.735 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at Completion/ termination (Month 36): 13-<16 years | 3.62 score on a scale | Standard Deviation 5.471 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at End of Epoch 2: 2-4 years | 8.16 score on a scale | Standard Deviation 17.73 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at End of Epoch 2: 5-7 years | -4.59 score on a scale | Standard Deviation 16.266 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at End of Epoch 2: 8-12 years | -1.98 score on a scale | Standard Deviation 14.027 |
| Epoch 1 + Epoch 2 | Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | Change From Baseline at End of Epoch 2: 13-<16 years | -2.45 score on a scale | Standard Deviation 8.807 |
Secondary
Health Resource Utilization: Days Not Able to go to School or Work, or to Perform Normal Daily Activities
Days not able to go to school or work, or to perform normal daily activities due to infection or other illnesses were calculated as days not able to go to school or work, or to perform normal daily activities due to infection or other illnesses per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all participants in the analysis set, divided by 365.25.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 1 + Epoch 2 | Health Resource Utilization: Days Not Able to go to School or Work, or to Perform Normal Daily Activities | 4.28 days per participant-year |
Secondary
Health Resource Utilization: Days on Antibiotics
Days on antibiotics were calculated as days on antibiotics per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all participants in the analysis set, divided by 365.25.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 1 + Epoch 2 | Health Resource Utilization: Days on Antibiotics | 26.77 days per participant-year |
Secondary
Health Resource Utilization: Number of Days Hospitalized Per Participant-Year
Number of days hospitalized were calculated as number of days hospitalized per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all participants in the analysis set, divided by 365.25.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 1 + Epoch 2 | Health Resource Utilization: Number of Days Hospitalized Per Participant-Year | 0.21 days per participant-year |
Secondary
Health Resource Utilization: Number of Hospitalizations
Number of hospitalizations, indication for the hospitalization (infection or non-infection) were calculated as number of hospitalizations, indication for the hospitalization (infection or non-infection) per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all participants in the analysis set, divided by 365.25.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 1 + Epoch 2 | Health Resource Utilization: Number of Hospitalizations | 0.08 hospitalizations per participant-year |
Secondary
HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score
The EQ-5D is a validated, self-administered assessment of overall health consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Participants were asked to describe their health state that day by choosing 1 of 3 responses that reflect the levels of severity for each of the five dimensions: no problems, some or moderate problems, or extreme problems. The domain scores are calculated with higher scores indicating worsening health status. The EQ-5D also includes a standard vertical 20-cm visual analogue scale (similar to a thermometer) for recording a participant's rating of their current HRQoL state, which ranged from 0 to 100, where 0 indicated worst imaginable health state and 100 was best imaginable health state. End of Epoch 2 summarizes all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1).
Time frame: Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
Population: SAS included all participants who received at least one dose of HyQvia. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Baseline: Visual Analogue Scale (VAS) Score | 82.84 score on a scale | Standard Deviation 16.806 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Baseline: Mobility | 1.07 score on a scale | Standard Deviation 0.258 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Baseline: Self-care | 1.16 score on a scale | Standard Deviation 0.485 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Baseline: Usual Activities | 1.14 score on a scale | Standard Deviation 0.413 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Baseline: Pain/ Discomfort | 1.28 score on a scale | Standard Deviation 0.454 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Baseline: Anxiety/ Depression | 1.28 score on a scale | Standard Deviation 0.549 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Epoch 2 Month 12: VAS Score | 0.64 score on a scale | Standard Deviation 23.504 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Epoch 2 Month 12: Mobility | -0.09 score on a scale | Standard Deviation 0.292 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Epoch 2 Month 12: Self-care | -0.12 score on a scale | Standard Deviation 0.415 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Epoch 2 Month 12: Usual Activities | 0.03 score on a scale | Standard Deviation 0.394 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Epoch 2 Month 12: Pain/ Discomfort | 0.18 score on a scale | Standard Deviation 0.528 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Epoch 2 Month 12: Anxiety/ Depression | -0.06 score on a scale | Standard Deviation 0.556 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Completion/ Termination (Month 36): VAS Score | -8.93 score on a scale | Standard Deviation 26.993 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Completion/ Termination (Month 36): Mobility | 0.00 score on a scale | Standard Deviation 0 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Completion/ Termination (Month 36): Self-care | 0.00 score on a scale | Standard Deviation 0 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Completion/ Termination (Month 36): Usual Activities | 0.00 score on a scale | Standard Deviation 0.535 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Completion/ Termination (Month 36): Pain/ Discomfort | -0.07 score on a scale | Standard Deviation 0.594 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at Completion/ Termination (Month 36): Anxiety/ Depression | -0.27 score on a scale | Standard Deviation 0.594 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at End of Epoch 2: VAS Score | -2.83 score on a scale | Standard Deviation 24.895 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at End of Epoch 2: Mobility | -0.07 score on a scale | Standard Deviation 0.264 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at End of Epoch 2: Self-care | -0.10 score on a scale | Standard Deviation 0.374 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at End of Epoch 2: Usual Activities | 0.00 score on a scale | Standard Deviation 0.387 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at End of Epoch 2: Pain/ Discomfort | 0.07 score on a scale | Standard Deviation 0.565 |
| Epoch 1 + Epoch 2 | HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | Change From Baseline at End of Epoch 2: Anxiety/ Depression | -0.10 score on a scale | Standard Deviation 0.539 |
Secondary
Number of Participants Who Developed Positive Titer (≥160) of Binding or Neutralizing Antibodies to rHuPH20
Number of participants who developed positive titer (rHuPH20 titer ≥160) of binding antibodies to rHuPH20 was reported. Neutralizing antibodies were only tested if the participant had a titer of ≥160 of binding antibodies. Participants with multiple assessments of titer of ≥160 of binding antibodies are counted only once.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: FAS included all participants who provided informed consent, and met enrollment eligibility.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Epoch 1 + Epoch 2 | Number of Participants Who Developed Positive Titer (≥160) of Binding or Neutralizing Antibodies to rHuPH20 | 1 Participants |
Secondary
Number of Participants With All Related (Causally) and/or Temporally Associated TEAEs Excluding Infections
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants with any related (causally) and/or temporally associated TEAEs (excluding infections) was reported. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion.
Time frame: From beginning of infusion up to 72 hours post infusion
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Epoch 1 + Epoch 2 | Number of Participants With All Related (Causally) and/or Temporally Associated TEAEs Excluding Infections | 27 Participants |
| Epoch 2 | Number of Participants With All Related (Causally) and/or Temporally Associated TEAEs Excluding Infections | 35 Participants |
Secondary
Number of Participants With All Temporally Associated TEAEs Excluding Infections
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced all temporally associated TEAEs, related or not related, was reported.
Time frame: From beginning of infusion up to 72 hours post infusion
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Epoch 1 + Epoch 2 | Number of Participants With All Temporally Associated TEAEs Excluding Infections | 27 Participants |
| Epoch 2 | Number of Participants With All Temporally Associated TEAEs Excluding Infections | 35 Participants |
Secondary
Number of Participants With All Treatment Emergent Adverse Events (TEAEs) Excluding Infections, Related and Not Related
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced TEAEs, related or not related, was reported.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Number of Participants With All Treatment Emergent Adverse Events (TEAEs) Excluding Infections, Related and Not Related | TEAE: Related | 25 Participants |
| Epoch 1 + Epoch 2 | Number of Participants With All Treatment Emergent Adverse Events (TEAEs) Excluding Infections, Related and Not Related | TEAE: Not Related | 16 Participants |
| Epoch 2 | Number of Participants With All Treatment Emergent Adverse Events (TEAEs) Excluding Infections, Related and Not Related | TEAE: Related | 31 Participants |
| Epoch 2 | Number of Participants With All Treatment Emergent Adverse Events (TEAEs) Excluding Infections, Related and Not Related | TEAE: Not Related | 36 Participants |
Secondary
Number of Participants With Local TEAEs Excluding Infections, Related and Not Related
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced local TEAEs, related or not related, was reported.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Number of Participants With Local TEAEs Excluding Infections, Related and Not Related | Local TEAE: Related | 22 Participants |
| Epoch 1 + Epoch 2 | Number of Participants With Local TEAEs Excluding Infections, Related and Not Related | Local TEAE: Not Related | 2 Participants |
| Epoch 2 | Number of Participants With Local TEAEs Excluding Infections, Related and Not Related | Local TEAE: Related | 28 Participants |
| Epoch 2 | Number of Participants With Local TEAEs Excluding Infections, Related and Not Related | Local TEAE: Not Related | 6 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) Excluding Infections, Related and Not Related
An SAE is defined as an untoward medical occurrence that at any dose is fatal, life-threatening, requires inpatient hospitalization or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event. Number of participants who experienced SAEs, related or not related, was reported.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: Safety Analysis Set (SAS) included all participants who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Number of Participants With Serious Adverse Events (SAEs) Excluding Infections, Related and Not Related | SAE: Related | 0 Participants |
| Epoch 1 + Epoch 2 | Number of Participants With Serious Adverse Events (SAEs) Excluding Infections, Related and Not Related | SAE: Not Related | 0 Participants |
| Epoch 2 | Number of Participants With Serious Adverse Events (SAEs) Excluding Infections, Related and Not Related | SAE: Related | 0 Participants |
| Epoch 2 | Number of Participants With Serious Adverse Events (SAEs) Excluding Infections, Related and Not Related | SAE: Not Related | 1 Participants |
Secondary
Number of Participants With Systemic TEAEs Excluding Infections, Related and Not Related
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced systemic TEAEs, related or not related, was reported.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Number of Participants With Systemic TEAEs Excluding Infections, Related and Not Related | Systemic TEAE: Not Related | 16 Participants |
| Epoch 1 + Epoch 2 | Number of Participants With Systemic TEAEs Excluding Infections, Related and Not Related | Systemic TEAE: Related | 12 Participants |
| Epoch 2 | Number of Participants With Systemic TEAEs Excluding Infections, Related and Not Related | Systemic TEAE: Related | 20 Participants |
| Epoch 2 | Number of Participants With Systemic TEAEs Excluding Infections, Related and Not Related | Systemic TEAE: Not Related | 33 Participants |
Secondary
Percentage of Participants Who Developed Positive Titer (≥160) of Binding or Neutralizing Antibodies to rHuPH20
Percentage of participants who developed positive titer (rHuPH20 titer ≥160) of binding antibodies to rHuPH20 was reported. Neutralizing antibodies were only tested if the participant had a titer of ≥160 of binding antibodies. Participants with multiple assessments of titer of ≥160 of binding antibodies are counted only once. Percentages are rounded off to whole number at the nearest decimal.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: FAS included all participants who provided informed consent, and met enrollment eligibility.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 1 + Epoch 2 | Percentage of Participants Who Developed Positive Titer (≥160) of Binding or Neutralizing Antibodies to rHuPH20 | 2.3 percentage of participants |
Secondary
Percentage of Participants With Any TEAEs Excluding Infections
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Percentages are rounded off to whole number at the nearest decimal.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 1 + Epoch 2 | Percentage of Participants With Any TEAEs Excluding Infections | 65.9 percentage of participants |
| Epoch 2 | Percentage of Participants With Any TEAEs Excluding Infections | 93.0 percentage of participants |
Secondary
Rate of All TEAEs Excluding Infections, Related and Not Related, Per Infusion
Rate of all TEAEs per infusion was calculated as number of any adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of any adverse reactions per infusion (excluding infections) was reported.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Rate of All TEAEs Excluding Infections, Related and Not Related, Per Infusion | TEAE: Related | 0.675 adverse reaction event per infusion |
| Epoch 1 + Epoch 2 | Rate of All TEAEs Excluding Infections, Related and Not Related, Per Infusion | TEAE: Not Related | 0.270 adverse reaction event per infusion |
| Epoch 2 | Rate of All TEAEs Excluding Infections, Related and Not Related, Per Infusion | TEAE: Related | 0.397 adverse reaction event per infusion |
| Epoch 2 | Rate of All TEAEs Excluding Infections, Related and Not Related, Per Infusion | TEAE: Not Related | 0.262 adverse reaction event per infusion |
Secondary
Rate of All Temporally Associated TEAEs Excluding Infections Per Infusion
Rate of all temporally associated TEAEs per infusion was calculated as number of all temporally associated TEAEs/total number of infusions administered to participants in the analysis set. Rate of all temporally associated TEAEs per infusion (excluding infections) was reported.
Time frame: From beginning of infusion up to 72 hours post infusion
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 1 + Epoch 2 | Rate of All Temporally Associated TEAEs Excluding Infections Per Infusion | 0.722 temporally associated TEAEs per infusion |
| Epoch 2 | Rate of All Temporally Associated TEAEs Excluding Infections Per Infusion | 0.460 temporally associated TEAEs per infusion |
Secondary
Rate of Local TEAEs Excluding Infections, Related and Not Related, Per Infusion
Rate of local TEAEs per infusion was calculated as number of local TEAEs/total number of infusions administered to participants in the analysis set. Rate of local TEAEs per infusion (excluding infections) was reported.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Rate of Local TEAEs Excluding Infections, Related and Not Related, Per Infusion | Local TEAE: Related | 0.460 local TEAEs per infusion |
| Epoch 1 + Epoch 2 | Rate of Local TEAEs Excluding Infections, Related and Not Related, Per Infusion | Local TEAE: Not Related | 0.016 local TEAEs per infusion |
| Epoch 2 | Rate of Local TEAEs Excluding Infections, Related and Not Related, Per Infusion | Local TEAE: Related | 0.212 local TEAEs per infusion |
| Epoch 2 | Rate of Local TEAEs Excluding Infections, Related and Not Related, Per Infusion | Local TEAE: Not Related | 0.013 local TEAEs per infusion |
Secondary
Rate of Participants With All Related (Causally) and/or Temporally Associated TEAEs Excluding Infections Per Infusion
Rate of any related (causally) and/or temporally associated TEAEs per infusion was calculated as number of related and/or temporally associated adverse events/ total number of infusions administered to participants in the analysis set. TEAEs recorded in the study database as possibly related or probably related to HYQVIA are considered HYQVIA-related adverse events. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Rate of any related (causally) and/or temporally associated TEAEs per infusion (excluding infections) was reported.
Time frame: From beginning of infusion up to 72 hours post infusion
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Epoch 1 + Epoch 2 | Rate of Participants With All Related (Causally) and/or Temporally Associated TEAEs Excluding Infections Per Infusion | 0.762 related temporally TEAEs per infusion |
| Epoch 2 | Rate of Participants With All Related (Causally) and/or Temporally Associated TEAEs Excluding Infections Per Infusion | 0.482 related temporally TEAEs per infusion |
Secondary
Rate of SAEs Excluding Infections, Related and Not Related, Per Infusion
Rate of SAEs per infusion was calculated as number of serious adverse events/total number of infusions administered to participants in the analysis set. Rate of SAEs per infusion (excluding infections) was reported.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Rate of SAEs Excluding Infections, Related and Not Related, Per Infusion | SAE: Related | 0.0 SAEs per infusion |
| Epoch 1 + Epoch 2 | Rate of SAEs Excluding Infections, Related and Not Related, Per Infusion | SAE: Not Related | 0.0 SAEs per infusion |
| Epoch 2 | Rate of SAEs Excluding Infections, Related and Not Related, Per Infusion | SAE: Related | 0.0 SAEs per infusion |
| Epoch 2 | Rate of SAEs Excluding Infections, Related and Not Related, Per Infusion | SAE: Not Related | 0.002 SAEs per infusion |
Secondary
Rate of Systemic TEAEs Excluding Infections, Related and Not Related, Per Infusion
Rate of systemic TEAEs per infusion was calculated as number of systemic TEAEs/total number of infusions administered to participants in the analysis set. Rate of systemic TEAEs per infusion (excluding infections) was reported.
Time frame: From first dose of study drug up to EOS (up to 4 years 9 months)
Population: SAS included all participants who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Rate of Systemic TEAEs Excluding Infections, Related and Not Related, Per Infusion | Systemic TEAE: Related | 0.214 systemic TEAEs per infusion |
| Epoch 1 + Epoch 2 | Rate of Systemic TEAEs Excluding Infections, Related and Not Related, Per Infusion | Systemic TEAE: Not Related | 0.254 systemic TEAEs per infusion |
| Epoch 2 | Rate of Systemic TEAEs Excluding Infections, Related and Not Related, Per Infusion | Systemic TEAE: Related | 0.185 systemic TEAEs per infusion |
| Epoch 2 | Rate of Systemic TEAEs Excluding Infections, Related and Not Related, Per Infusion | Systemic TEAE: Not Related | 0.250 systemic TEAEs per infusion |
Secondary
Rate Represented as Mean Number of All Infections Per Participant-year
The rate of all infections was defined as the mean number of all infections per participant-year. Number of all infections was calculated as number of infections per participant-year.
Time frame: From first dose of study drug up to end of Study Epoch 2 (up to approximately 37.2 months)
Population: FAS included all participants who provided informed consent, and met enrollment eligibility.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Rate Represented as Mean Number of All Infections Per Participant-year | 3.12 infections per participant-year | Standard Error 0.45 |
Secondary
Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score
The LQI is a validated questionnaire assessing participant perceptions of their HRQoL and their treatment specifically among participants who use IgG therapy. This questionnaire covers 4 domains: treatment interferences, therapy-related problems, therapy setting, and treatment costs. The LQI domains are scored from 0 to 100, with higher scores associated with better IgG treatment satisfaction. End of Epoch 2 summarizes all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1).
Time frame: Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
Population: SAS included all participants who received at least one dose of HyQvia. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Baseline: Treatment Interferences | 69.77 score on a scale | Standard Deviation 17.518 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Baseline: Therapy-related Problems | 65.21 score on a scale | Standard Deviation 17.08 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Baseline: Therapy Setting | 85.66 score on a scale | Standard Deviation 14.61 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Baseline: Treatment Costs | 60.85 score on a scale | Standard Deviation 27.31 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at Epoch 2 Month 12: Treatment Interferences | 4.71 score on a scale | Standard Deviation 18.419 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at Epoch 2 Month 12: Therapy-related Problems | 4.67 score on a scale | Standard Deviation 17.67 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at Epoch 2 Month 12: Therapy Setting | -6.23 score on a scale | Standard Deviation 23.189 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at Epoch 2 Month 12: Treatment Costs | 4.55 score on a scale | Standard Deviation 36.33 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at Completion/Termination (Month 36): Treatment Interferences | -10.52 score on a scale | Standard Deviation 23.85 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at Completion/Termination (Month 36): Therapy-related Problems | -13.39 score on a scale | Standard Deviation 31.656 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at Completion/Termination (Month 36): Therapy Setting | -15.87 score on a scale | Standard Deviation 27.808 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at Completion/Termination (Month 36): Treatment Costs | -1.19 score on a scale | Standard Deviation 32.826 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at End of Epoch 2: Treatment Interferences | 1.49 score on a scale | Standard Deviation 20.908 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at End of Epoch 2: Therapy-related Problems | 0.41 score on a scale | Standard Deviation 24.399 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at End of Epoch 2: Therapy Setting | -10.16 score on a scale | Standard Deviation 24.718 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | Change From Baseline at End of Epoch 2: Treatment Costs | 4.27 score on a scale | Standard Deviation 35.164 |
Secondary
Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score
The TSQM-9 is a 9-item, validated, self-administered instrument to assess participant satisfaction with medication, which assesses 3 domains: effectiveness, convenience, and global satisfaction. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction. End of Epoch 2 summarizes all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1).
Time frame: Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
Population: SAS included all participants who received at least one dose of HyQvia. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analysis at a specified timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Baseline: Effectiveness | 74.81 score on a scale | Standard Deviation 15.494 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Baseline: Convenience | 66.15 score on a scale | Standard Deviation 16.436 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Baseline: Global Satisfaction | 79.07 score on a scale | Standard Deviation 16.525 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Change From Baseline at Epoch 2, Month 12: Effectiveness | 6.40 score on a scale | Standard Deviation 16.204 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Change From Baseline at Epoch 2, Month 12: Convenience | 2.19 score on a scale | Standard Deviation 19.834 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Change From Baseline at Epoch 2, Month 12: Global Satisfaction | 4.76 score on a scale | Standard Deviation 18.529 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Change From Baseline at Completion/ termination (Month 36): Effectiveness | -12.70 score on a scale | Standard Deviation 33.577 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Change From Baseline at Completion/ termination (Month 36): Convenience | -7.14 score on a scale | Standard Deviation 20.375 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Change From Baseline at Completion/ termination (Month 36): Global Satisfaction | -17.35 score on a scale | Standard Deviation 36.283 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Change From Baseline at end of Epoch 2: Effectiveness | 3.52 score on a scale | Standard Deviation 20.591 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Change From Baseline at end of Epoch 2: Convenience | -0.81 score on a scale | Standard Deviation 20.244 |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | Change From Baseline at end of Epoch 2: Global Satisfaction | -0.17 score on a scale | Standard Deviation 24.406 |
Secondary
Treatment Preference and Satisfaction: Number of Participants Who Completed Treatment Preference Questionnaire
The treatment preference questionnaire, internally developed by the study sponsor, is a self-administered, non-validated scale assessing participant preference for various attributes of immunoglobulin G (IgG) therapy.End of Epoch 2 summarizes all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1).
Time frame: Study Epoch 2: Up to Month 36
Population: SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Number of Participants Who Completed Treatment Preference Questionnaire | Month 12 | 34 Participants |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Number of Participants Who Completed Treatment Preference Questionnaire | Completion/ Termination (Month 36) | 14 Participants |
| Epoch 1 + Epoch 2 | Treatment Preference and Satisfaction: Number of Participants Who Completed Treatment Preference Questionnaire | End of Epoch 2 | 42 Participants |