Primary Immunodeficiency Diseases (PID)
Conditions
Brief summary
The purpose of the study is to acquire additional data on safety, tolerability and immunogenicity of HyQvia in pediatric (age two to \<18 years) patients with Primary Immunodeficiency Diseases (PIDD)
Interventions
Sponsors
Baxalta Innovations GmbH, now part of Shire
Baxalta now part of Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Participant must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the International Union of Immunological Societies (IUIS) Scientific Committee 2015 prior to enrollment. The diagnosis must be confirmed by the sponsor´s Medical Director prior to first treatment with investigational product (IP) in the study. 2. Participant is at least two and below 18 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 body weight (BW)/four weeks and a maximum dose equivalent to 1000 mg/kg 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 amino transferase (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 (\< 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 \< 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 |
|---|---|---|
| Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | An Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as possibly related or probably related to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any severe related TEAEs (excluding infections) was reported. |
| Safety: Rate of Any Severe Related TEAEs Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | An AE was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as possibly related or probably related to HYQVIA were considered HYQVIA-related adverse events. Severe related TEAEs rate per infusion was calculated as number of severe related TEAEs/total number of infusions administered to participants in the analysis set. Rate of any severe related TEAEs per infusion (excluding infections) was reported. |
| Safety: Number of Participants With Any Related Serious TEAEs Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs that were recorded as possibly related or probably related to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any related serious TEAEs per infusion (excluding infections) was reported. |
| Safety: Rate of Any Related Serious TEAEs Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in-patient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs that were recorded as possibly related or probably related to HYQVIA were considered HYQVIA-related adverse events. Rate of related serious TEAEs per infusion was calculated as number of related serious TEAEs/total number of infusions administered to participants in the analysis set. Rate of any related serious TEAEs per Infusion (excluding infections) was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Haemophilus Influenzae B IgG at Month 12 | Baseline, Month 12 | Change from baseline in trough levels of specific antibodies in Haemophilus influenzae B IgG at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. |
| Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 | Up to 20 months | Percentage of participants who achieved a treatment interval of three or four weeks in Epoch 2 was reported. |
| Safety: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 up to 12 Months | Up to 12 months | Percentage of participants who maintained a treatment interval of three or four weeks in Epoch 2 up to 12 months was reported. |
| Safety: Number of Participants With Local TEAEs (Excluding Infections) | From start of study drug administration up to 20 months | TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Number of Participants with local TEAEs (excluding infections) was reported. |
| Safety: Rate of Local TEAEs Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | Rate of local TEAEs per infusion was calculated as number of local adverse events/total number of infusions administered to participants in the analysis set. Only events are included which start prior to participants start date of non-response. Rate of local TEAEs per infusion (excluding infections) was reported. |
| Safety: Number of Participants With Local Adverse Reaction (Excluding Infections) | From start of study drug administration up to 20 months | Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with local adverse reactions (excluding infections) was reported. |
| Safety: Rate of Local Adverse Reaction Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | Rate of local adverse reaction per infusion was calculated as number of local adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of local adverse reactions per infusion (excluding infections) was reported. |
| Safety: Number of Participants With Systemic TEAEs (Excluding Infections) | From start of study drug administration up to 20 months | TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Number of participants with systemic TEAEs (excluding infections) was reported.. |
| Safety: Rate of Systemic TEAEs Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | Rate of systemic TEAEs per infusion was calculated as number of systemic adverse events/total number of infusions administered to participants in the analysis set. Rate of systemic TEAEs per infusion was assessed based on events per infusion. |
| Safety: Number of Participants With Systemic Adverse Reaction (Excluding Infections) | From start of study drug administration up to 20 months | Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with systemic adverse reaction (excluding infections) was reported. |
| Safety: Rate of Systemic Adverse Reaction Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | Rate of Systemic adverse reactions per infusion was calculated as number of systemic adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of systemic adverse reactions per infusion (excluding infections) was reported. |
| Safety: Number of Participants With Any TEAEs (Excluding Infections) | From start of study drug administration up to 20 months | TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Number of participants with any TEAEs (excluding infections) was reported. |
| Safety: Rate of TEAEs Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | Rate of TEAEs per infusion was calculated as number of adverse events/total number of infusions administered to participants in the analysis set. Rate of TEAEs per infusion (excluding infections) was reported. |
| Safety: Number of Participants With Any Adverse Reactions (Excluding Infections) | From start of study drug administration up to 20 months | Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with any adverse reactions (excluding infections) was reported. |
| Safety: Rate of Any Adverse Reaction Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | Rate of all adverse reactions per infusion was calculated as number of adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of any adverse reactions per infusion (excluding infections) was reported. |
| Safety: Number of Participants With Any Temporally Associated TEAEs (Excluding Infections) | From start of study drug administration up to 20 months | Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Number of participants with any temporally associated TEAEs (excluding infections) was reported. |
| Safety: Rate of Any Temporally Associated TEAEs Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | Rate of any temporally associated TEAEs per infusion was calculated as number of temporally associated adverse events/total number of infusions administered to participants in the analysis set. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Rate of any temporally associated TEAEs per infusion (excluding infections) was reported. |
| Safety: Number of Participants With Any Related (Causally) and/or Temporally Associated TEAEs (Excluding Infections) | From start of study drug administration up to 20 months | 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. |
| Safety: Rate of Any Related (Causally) and/or Temporally Associated TEAEs Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | 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. |
| Safety: Number of Participants With Any Serious TEAEs (Excluding Infections) | From start of study drug administration up to 20 months | Serious TEAE were the AEs that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in-patient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Number of participants with any serious TEAEs (excluding infections) was reported. |
| Safety: Rate of Serious TEAEs Per Infusion (Excluding Infections) | From start of study drug administration up to 20 months | Rate of serious TEAEs per infusion was calculated as number of serious adverse events/total number of infusions administered to participants in the analysis set. Rate of serious TEAEs per infusion (excluding infections) was reported. |
| Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20 | From start of study drug administration up to 20 months | Number of participants who developed positive titer (\>=160) of binding or neutralizing antibodies to rHuPH20 was reported. |
| Other Analysis: Number of Infusions Per Month | Up to 20 months | Number of infusions per month was calculated as total number of infusions per duration of treatment (days) \* 30.4 days per month. |
| Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Infusion | Up to 20 months | Number of infusion sites (needle-sticks) per infusion was calculated as total number of infusion sites / total number of infusions. Only infusions with complete data available were included. |
| Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Month | Up to 20 months | Number of infusion sites per month was calculated as total number of infusion sites / duration of treatment (days) \* 30.4 days. Only infusions with complete data available were included. |
| Other Analysis: Duration of Infusion | From start of study drug administration up to 20 months. | The duration of infusion was defined as the difference between the end time and the start time of the HyQvia infusion. |
| Other Analysis: Maximum Infusion Rate Per Site | Up to 20 months | Maximum infusion rate per site was reported. |
| Other Analysis: Infusion Volume Per Site | Up to 20 months | Infusion volume per site was calculated as actual IgG volume (milliliter \[mL\]) / total number of infusion sites (hour) used. |
| Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE | Up to 20 months | Number of infusions that were interrupted or Stopped due to an AE was reported. |
| Other Analysis: Number of Weeks to Reach Final 3 or 4-week Dose Interval in Epoch 1 | Up to 20 months | Final dose interval, defined as three or four weeks infusion interval in Epoch 1 of treatment period, was reported. |
| Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | Baseline up to 20 months | PedsQL Generic Core Scale (GCS) was used for QOL assessment. It encompasses 4 dimensions (physical functioning \[PF\], emotional functioning \[EF\], social functioning \[SF\], school functioning \[ScF\]). Age groups are: Toddler (2-4 years), Young child (5-7 years), Child (8-12 years), and Teens (13-\<18 years). Depending on the participants age, the questionnaire may be completed by either the participant or the parent/caregiver as appropriate. For the Toddler group, the PedsQL GCS consisted of 21 items, using a 5-point Likert scale (0 to 4); for all other groups, the PedsQL consisted of 23 items, with a 3-point Likert scale (0, 2, 4) for the young child, and a 5-point Likert scale for the child and teens groups. All Scores were transformed on a scale from 0 to 100 where 0=100, 1=75, 2=50, 3=25, and 4=0. Higher scores indicate better quality of life. A negative change from baseline indicates worse quality of life. Baseline: last non-missing value before the initial dose of HYQVIA. |
| Efficacy: Change From Baseline in Total Serum Trough Levels of Immunoglobulin G (IgG) at Month 12 | Baseline, Month 12 | Change from baseline in total serum trough levels of IgG in Epoch 1 and 2 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. |
| HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) | Baseline up to 20 months | TSQM-9 is a 9-item, validated, self-administered instrument to assess participants satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. The lowest possible score (1 for each item and 3 for all 3 subscales) was subtracted from the composite score and divided by the greatest possible score range. The greatest range was (7-1)\*3 items = 18 for the effectiveness and convenience, and (5-1)\*3 items = 12 for global satisfaction . The item scores of each of the 3 domains are summed and transformed to create a score of 0 (extremely dissatisfied) to 100 (extremely satisfied). Higher score indicated greater satisfaction in that domain. A negative change from baseline indicates less satisfaction in that domain. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. |
| HRQoL: Change From Baseline in EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) | Baseline up to 20 months | EQ-5D considered five attributes of quality of life evaluation, that is, mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each dimension had five possible levels: 1 (no problems); 2 (slight problems); 3 (moderate problems); 4 (severe problems), and; 5 (extreme problems). The participants rating of their current HRQoL state was recorded using a standard vertical 20-cm visual analog scale (EQ-VAS), which ranged from 0 to 100, where 0 indicated worst imaginable health state and 100 was best imaginable health state. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. A negative change from baseline indicates worse health state. |
| Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 | Baseline, Month 12 | Change from baseline in Serum trough levels of IgG subclasses 1, 2, 3, and 4 in Epoch 1 and 2 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. |
| Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Clostridium Tetani Toxoid IgG at Month 12 | Baseline, Month 12 | Change from baseline in trough levels of specific antibodies in clostridium tetani toxoid IgG at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. Here, IU/ml was defined as International units per milliliter. |
| Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Hepatitis B Virus (HBV) at Month 12 | Baseline, Month 12 | Change from baseline in trough levels of specific antibodies in HBV at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. |
Countries
Czechia, Denmark, France, Greece, Hungary, Slovakia, Sweden, United Kingdom
Participant flow
Recruitment details
The study was conducted at 16 sites from 30 May 2017 to 15 January 2021. A total of 42 participants were enrolled and treated in this study. This study consisted of 3 treatment periods: Epoch 1, Epoch 2 and Epoch 3. Participant with anti-rHuPH20 antibody titer greater than or equal to (\>=) 160 during Epoch 1 or Epoch 2 and who experienced either a related serious adverse event or related severe adverse event were followed to Epoch 3.
Pre-assignment details
Participants who were treated with HyQvia in Epoch 1 followed by Epoch 2 were referred to as HyQvia new starters and participants who started directly in Epoch 2 were referred to as HyQvia pre-treated. 1 participant from HyQvia new starters group discontinued Epoch 2 and entered Epoch 3 due to a severe related adverse event. Participant did not receive HyQvia treatment in Epoch 3. Therefore, no further safety and efficacy data were collected in Epoch 3.
Participants by arm
| Arm | Count |
|---|---|
| HyQvia New Starters Participants who were treated with non-HyQvia treatment by time of enrollment were enrolled in Epoch 1 (ramp-up) and treated with HyQvia SC with a dose or interval ramp-up period of up to 6 weeks. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment. Dosage Frequency was one treatment interval of one week, then one treatment interval of two weeks, then one treatment interval of three weeks (for participants in whom treatment was expected to be every four weeks). The ramp-up period was followed by Epoch 2 (no ramp-up) with HyQvia SC treatment at every 3 or 4 weeks, depending on the participant's previous dosing schedule and the discretion of the investigator and participant, for up to 20 months. | 23 |
| HyQvia Pre-treated Participants already treated with HYQVIA by the time of enrollment were directly enrolled in Epoch 2 and treated with HyQvia SC at every 3 or 4 weeks for up to 20 months. HyQvia dose was planned to be equivalent to 100% (±5%) of pre-study treatment with a dosage frequency of once every three or four weeks, based on the participants previous dosing schedule and the discretion of the investigator and participant. | 19 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | HyQvia Pre-treated | Total | HyQvia New Starters |
|---|---|---|---|
| Age, Continuous | 11.7 Years STANDARD_DEVIATION 4.33 | 11 Years STANDARD_DEVIATION 4.07 | 10.3 Years STANDARD_DEVIATION 3.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 42 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 41 Participants | 22 Participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 5 Participants |
| Sex: Female, Male Male | 16 Participants | 34 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 19 |
| other Total, other adverse events | 22 / 23 | 14 / 19 |
| serious Total, serious adverse events | 2 / 23 | 5 / 19 |
Outcome results
Primary
Safety: Number of Participants With Any Related Serious TEAEs Per Infusion (Excluding Infections)
TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs that were recorded as possibly related or probably related to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any related serious TEAEs per infusion (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Any Related Serious TEAEs Per Infusion (Excluding Infections) | 0 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Any Related Serious TEAEs Per Infusion (Excluding Infections) | 0 Participants |
Primary
Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections)
An Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as possibly related or probably related to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any severe related TEAEs (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections) | 1 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections) | 0 Participants |
Primary
Safety: Rate of Any Related Serious TEAEs Per Infusion (Excluding Infections)
TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in-patient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs that were recorded as possibly related or probably related to HYQVIA were considered HYQVIA-related adverse events. Rate of related serious TEAEs per infusion was calculated as number of related serious TEAEs/total number of infusions administered to participants in the analysis set. Rate of any related serious TEAEs per Infusion (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of Any Related Serious TEAEs Per Infusion (Excluding Infections) | 0 Number of Related Serious TEAEs/Infusion |
| HyQvia Pre-treated | Safety: Rate of Any Related Serious TEAEs Per Infusion (Excluding Infections) | 0 Number of Related Serious TEAEs/Infusion |
Primary
Safety: Rate of Any Severe Related TEAEs Per Infusion (Excluding Infections)
An AE was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as possibly related or probably related to HYQVIA were considered HYQVIA-related adverse events. Severe related TEAEs rate per infusion was calculated as number of severe related TEAEs/total number of infusions administered to participants in the analysis set. Rate of any severe related TEAEs per infusion (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of Any Severe Related TEAEs Per Infusion (Excluding Infections) | 0.004 Number of Severe Related TEAEs/Infusion |
| HyQvia Pre-treated | Safety: Rate of Any Severe Related TEAEs Per Infusion (Excluding Infections) | 0 Number of Severe Related TEAEs/Infusion |
Secondary
Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12
Change from baseline in Serum trough levels of IgG subclasses 1, 2, 3, and 4 in Epoch 1 and 2 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.
Time frame: Baseline, Month 12
Population: All participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HyQvia New Starters | Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 | IgG Subclass 1 : Changed at Month 12 | -0.813 g/L | Standard Deviation 1.1087 |
| HyQvia New Starters | Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 | IgG Subclass 3 : Changed at Month 12 | 0.000 g/L | Standard Deviation 0.3651 |
| HyQvia New Starters | Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 | IgG Subclass 2 : Changed at Month 12 | 0.000 g/L | Standard Deviation 0.8944 |
| HyQvia New Starters | Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 | IgG Subclass 4 : Changed at Month 12 | 0.094 g/L | Standard Deviation 0.0854 |
| HyQvia Pre-treated | Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 | IgG Subclass 4 : Changed at Month 12 | -0.027 g/L | Standard Deviation 0.0799 |
| HyQvia Pre-treated | Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 | IgG Subclass 1 : Changed at Month 12 | -0.467 g/L | Standard Deviation 1.5976 |
| HyQvia Pre-treated | Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 | IgG Subclass 2 : Changed at Month 12 | -0.667 g/L | Standard Deviation 1.3452 |
| HyQvia Pre-treated | Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12 | IgG Subclass 3 : Changed at Month 12 | 0.133 g/L | Standard Deviation 0.3519 |
Secondary
Efficacy: Change From Baseline in Total Serum Trough Levels of Immunoglobulin G (IgG) at Month 12
Change from baseline in total serum trough levels of IgG in Epoch 1 and 2 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.
Time frame: Baseline, Month 12
Population: Full analysis set included all participants who provide informed consent and meet enrollment eligibility. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HyQvia New Starters | Efficacy: Change From Baseline in Total Serum Trough Levels of Immunoglobulin G (IgG) at Month 12 | 0.035 Gram per liter (g/L) | Standard Deviation 1.6983 |
| HyQvia Pre-treated | Efficacy: Change From Baseline in Total Serum Trough Levels of Immunoglobulin G (IgG) at Month 12 | -0.709 Gram per liter (g/L) | Standard Deviation 2.6576 |
Secondary
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Clostridium Tetani Toxoid IgG at Month 12
Change from baseline in trough levels of specific antibodies in clostridium tetani toxoid IgG at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. Here, IU/ml was defined as International units per milliliter.
Time frame: Baseline, Month 12
Population: All participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure. Specific antibody data were not scheduled to be collected at Epoch 2 Month 0, so for most participants baseline could not be defined and change from baseline was not reported in HYQVIA Pre-treated arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HyQvia New Starters | Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Clostridium Tetani Toxoid IgG at Month 12 | -0.218 IU/ml | Standard Deviation 0.9345 |
Secondary
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Haemophilus Influenzae B IgG at Month 12
Change from baseline in trough levels of specific antibodies in Haemophilus influenzae B IgG at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.
Time frame: Baseline, Month 12
Population: All participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure. Specific antibody data were not scheduled to be collected at Epoch 2 Month 0, so for most participants baseline could not be defined and change from baseline was not reported in HYQVIA Pre-treated arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HyQvia New Starters | Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Haemophilus Influenzae B IgG at Month 12 | -0.017 Milligram per liter (mg/L) | Standard Deviation 0.9503 |
Secondary
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Hepatitis B Virus (HBV) at Month 12
Change from baseline in trough levels of specific antibodies in HBV at Month 12 was reported. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.
Time frame: Baseline, Month 12
Population: All participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, Overall number of Participants Analyzed signifies participants who were evaluable for this outcome measure. Specific antibody data were not scheduled to be collected at Epoch 2 Month 0, so for most participants baseline could not be defined and change from baseline was not reported in HYQVIA Pre-treated arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HyQvia New Starters | Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Hepatitis B Virus (HBV) at Month 12 | 167.875 International units per liter (IU/L) | Standard Deviation 147.4887 |
Secondary
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL)
PedsQL Generic Core Scale (GCS) was used for QOL assessment. It encompasses 4 dimensions (physical functioning \[PF\], emotional functioning \[EF\], social functioning \[SF\], school functioning \[ScF\]). Age groups are: Toddler (2-4 years), Young child (5-7 years), Child (8-12 years), and Teens (13-\<18 years). Depending on the participants age, the questionnaire may be completed by either the participant or the parent/caregiver as appropriate. For the Toddler group, the PedsQL GCS consisted of 21 items, using a 5-point Likert scale (0 to 4); for all other groups, the PedsQL consisted of 23 items, with a 3-point Likert scale (0, 2, 4) for the young child, and a 5-point Likert scale for the child and teens groups. All Scores were transformed on a scale from 0 to 100 where 0=100, 1=75, 2=50, 3=25, and 4=0. Higher scores indicate better quality of life. A negative change from baseline indicates worse quality of life. Baseline: last non-missing value before the initial dose of HYQVIA.
Time frame: Baseline up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, Overall number of Participants Analyzed signifies participants who are evaluable for this outcome measure and Number analyzed signifies participants who are evaluable for this outcome at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HyQvia New Starters | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | SF in Teens: Change up to 20 months | 1.67 Score on a scale | Standard Deviation 7.638 |
| HyQvia New Starters | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | PF in Child: Change up to 20 months | 7.81 Score on a scale | Standard Deviation 6.626 |
| HyQvia New Starters | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | EF in Child: Change up to 20 months | 5.00 Score on a scale | Standard Deviation 14.142 |
| HyQvia New Starters | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | PF in Teens: Change up to 20 months | -12.65 Score on a scale | Standard Deviation 12.726 |
| HyQvia New Starters | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | ScF in Child: Change up to 20 months | -12.50 Score on a scale | Standard Deviation 10.607 |
| HyQvia New Starters | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | SF in Child: Change up to 20 months | -20.00 Score on a scale | Standard Deviation 0 |
| HyQvia New Starters | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | ScF in Teens: Change up to 20 months | 1.67 Score on a scale | Standard Deviation 7.638 |
| HyQvia New Starters | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | EF in Teens: Change up to 20 months | -13.33 Score on a scale | Standard Deviation 7.638 |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | SF in Toddler: Change up to 20 months | 0.00 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | SF in Young child: Change up to 20 months | -35.00 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | SF in Child: Change up to 20 months | -40.00 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | SF in Teens: Change up to 20 months | 8.00 Score on a scale | Standard Deviation 11.511 |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | ScF in Toddler: Change up to 20 months | 25.00 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | ScF in Young child: Change up to 20 months | -45.00 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | ScF in Child: Change up to 20 months | -65.00 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | PF in Toddler: Change up to 20 months | -3.12 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | ScF in Teens: Change up to 20 months | -17.00 Score on a scale | Standard Deviation 24.135 |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | PF in Young child: Change up to 20 months | -31.25 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | PF in Child: Change up to 20 months | -71.88 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | PF in Teens: Change up to 20 months | 13.75 Score on a scale | Standard Deviation 24.664 |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | EF in Toddler: Change up to 20 months | 0.00 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | EF in Young child: Change up to 20 months | -25.00 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | EF in Child: Change up to 20 months | -20.00 Score on a scale | — |
| HyQvia Pre-treated | Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL) | EF in Teens: Change up to 20 months | 1.25 Score on a scale | Standard Deviation 14.307 |
Secondary
HRQoL: Change From Baseline in EuroQoL (Quality of Life)-5 Dimensions (EQ-5D)
EQ-5D considered five attributes of quality of life evaluation, that is, mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. Each dimension had five possible levels: 1 (no problems); 2 (slight problems); 3 (moderate problems); 4 (severe problems), and; 5 (extreme problems). The participants rating of their current HRQoL state was recorded using a standard vertical 20-cm visual analog scale (EQ-VAS), which ranged from 0 to 100, where 0 indicated worst imaginable health state and 100 was best imaginable health state. Baseline was defined as the last non-missing value before the initial dose of HYQVIA. A negative change from baseline indicates worse health state.
Time frame: Baseline up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, Overall number of Participants Analyzed signifies participants who are evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HyQvia New Starters | HRQoL: Change From Baseline in EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) | -8.60 Score on a scale | Standard Deviation 11.149 |
| HyQvia Pre-treated | HRQoL: Change From Baseline in EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) | -4.43 Score on a scale | Standard Deviation 15.447 |
Secondary
HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9)
TSQM-9 is a 9-item, validated, self-administered instrument to assess participants satisfaction with medication. It consists of 3 subscales: effectiveness, convenience and global satisfaction. The scores were computed by adding items for each domain, i.e. 1 to 3 for effectiveness, 4 - 6 for convenience and 7 to 9 for global satisfaction. The lowest possible score (1 for each item and 3 for all 3 subscales) was subtracted from the composite score and divided by the greatest possible score range. The greatest range was (7-1)\*3 items = 18 for the effectiveness and convenience, and (5-1)\*3 items = 12 for global satisfaction . The item scores of each of the 3 domains are summed and transformed to create a score of 0 (extremely dissatisfied) to 100 (extremely satisfied). Higher score indicated greater satisfaction in that domain. A negative change from baseline indicates less satisfaction in that domain. Baseline was defined as the last non-missing value before the initial dose of HYQVIA.
Time frame: Baseline up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, Overall number of Participants Analyzed signifies participants who are evaluable for this outcome measure and Number analyzed signifies participants who are evaluable for this outcome at specific time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| HyQvia New Starters | HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) | Effectiveness: Change at 20 months | 12.96 Score on a scale | Standard Deviation 32.552 |
| HyQvia New Starters | HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) | Convenience: Change at 20 months | 14.81 Score on a scale | Standard Deviation 27.398 |
| HyQvia New Starters | HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) | Global satisfaction: Change 20 months | 11.90 Score on a scale | Standard Deviation 10.911 |
| HyQvia Pre-treated | HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) | Effectiveness: Change at 20 months | -0.92 Score on a scale | Standard Deviation 10.783 |
| HyQvia Pre-treated | HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) | Convenience: Change at 20 months | 4.63 Score on a scale | Standard Deviation 15.873 |
| HyQvia Pre-treated | HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) | Global satisfaction: Change 20 months | -2.38 Score on a scale | Standard Deviation 19.518 |
Secondary
Other Analysis: Duration of Infusion
The duration of infusion was defined as the difference between the end time and the start time of the HyQvia infusion.
Time frame: From start of study drug administration up to 20 months.
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HyQvia New Starters | Other Analysis: Duration of Infusion | 75.0 Minutes |
| HyQvia Pre-treated | Other Analysis: Duration of Infusion | 101.0 Minutes |
Secondary
Other Analysis: Infusion Volume Per Site
Infusion volume per site was calculated as actual IgG volume (milliliter \[mL\]) / total number of infusion sites (hour) used.
Time frame: Up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HyQvia New Starters | Other Analysis: Infusion Volume Per Site | 112.39 Milliliter per hour | Standard Deviation 71.427 |
| HyQvia Pre-treated | Other Analysis: Infusion Volume Per Site | 178.23 Milliliter per hour | Standard Deviation 98.523 |
Secondary
Other Analysis: Maximum Infusion Rate Per Site
Maximum infusion rate per site was reported.
Time frame: Up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HyQvia New Starters | Other Analysis: Maximum Infusion Rate Per Site | 181.54 Milliliter per hour per site (mL/h/site) | Standard Deviation 77.772 |
| HyQvia Pre-treated | Other Analysis: Maximum Infusion Rate Per Site | 171.73 Milliliter per hour per site (mL/h/site) | Standard Deviation 90.203 |
Secondary
Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Infusion
Number of infusion sites (needle-sticks) per infusion was calculated as total number of infusion sites / total number of infusions. Only infusions with complete data available were included.
Time frame: Up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HyQvia New Starters | Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Infusion | 1.65 Infusion sites (needle sticks)/Infusion | Standard Deviation 0.442 |
| HyQvia Pre-treated | Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Infusion | 1.25 Infusion sites (needle sticks)/Infusion | Standard Deviation 0.403 |
Secondary
Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Month
Number of infusion sites per month was calculated as total number of infusion sites / duration of treatment (days) \* 30.4 days. Only infusions with complete data available were included.
Time frame: Up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HyQvia New Starters | Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Month | 1.96 Infusion sites (needle sticks)/Month | Standard Deviation 0.78 |
| HyQvia Pre-treated | Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Month | 1.33 Infusion sites (needle sticks)/Month | Standard Deviation 0.634 |
Secondary
Other Analysis: Number of Infusions Per Month
Number of infusions per month was calculated as total number of infusions per duration of treatment (days) \* 30.4 days per month.
Time frame: Up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HyQvia New Starters | Other Analysis: Number of Infusions Per Month | 1.30 Infusion/Month |
| HyQvia Pre-treated | Other Analysis: Number of Infusions Per Month | 1.20 Infusion/Month |
Secondary
Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE
Number of infusions that were interrupted or Stopped due to an AE was reported.
Time frame: Up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HyQvia New Starters | Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE | Number of infusions interrupted | 4 Infusions |
| HyQvia New Starters | Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE | Number of infusions Stopped | 1 Infusions |
| HyQvia Pre-treated | Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE | Number of infusions interrupted | 0 Infusions |
| HyQvia Pre-treated | Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE | Number of infusions Stopped | 0 Infusions |
Secondary
Other Analysis: Number of Weeks to Reach Final 3 or 4-week Dose Interval in Epoch 1
Final dose interval, defined as three or four weeks infusion interval in Epoch 1 of treatment period, was reported.
Time frame: Up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia. Here, Overall number of Participants Analyzed signifies participants who are evaluable for this outcome measure. Data collection and analysis was not planned for HyQvia pre-treated group.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HyQvia New Starters | Other Analysis: Number of Weeks to Reach Final 3 or 4-week Dose Interval in Epoch 1 | 6.10 Weeks |
Secondary
Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20
Number of participants who developed positive titer (\>=160) of binding or neutralizing antibodies to rHuPH20 was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HyQvia New Starters | Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20 | Participants with positive titer (>=160) of binding antibodies | 0 Participants |
| HyQvia New Starters | Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20 | Participants with neutralizing antibodies | 0 Participants |
| HyQvia Pre-treated | Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20 | Participants with positive titer (>=160) of binding antibodies | 0 Participants |
| HyQvia Pre-treated | Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20 | Participants with neutralizing antibodies | 0 Participants |
Secondary
Safety: Number of Participants With Any Adverse Reactions (Excluding Infections)
Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with any adverse reactions (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Any Adverse Reactions (Excluding Infections) | 12 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Any Adverse Reactions (Excluding Infections) | 3 Participants |
Secondary
Safety: Number of Participants With Any Related (Causally) and/or Temporally Associated TEAEs (Excluding Infections)
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 start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Any Related (Causally) and/or Temporally Associated TEAEs (Excluding Infections) | 13 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Any Related (Causally) and/or Temporally Associated TEAEs (Excluding Infections) | 6 Participants |
Secondary
Safety: Number of Participants With Any Serious TEAEs (Excluding Infections)
Serious TEAE were the AEs that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in-patient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Number of participants with any serious TEAEs (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Any Serious TEAEs (Excluding Infections) | 0 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Any Serious TEAEs (Excluding Infections) | 3 Participants |
Secondary
Safety: Number of Participants With Any TEAEs (Excluding Infections)
TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Number of participants with any TEAEs (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Any TEAEs (Excluding Infections) | 18 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Any TEAEs (Excluding Infections) | 11 Participants |
Secondary
Safety: Number of Participants With Any Temporally Associated TEAEs (Excluding Infections)
Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Number of participants with any temporally associated TEAEs (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Any Temporally Associated TEAEs (Excluding Infections) | 13 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Any Temporally Associated TEAEs (Excluding Infections) | 6 Participants |
Secondary
Safety: Number of Participants With Local Adverse Reaction (Excluding Infections)
Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with local adverse reactions (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Local Adverse Reaction (Excluding Infections) | 11 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Local Adverse Reaction (Excluding Infections) | 3 Participants |
Secondary
Safety: Number of Participants With Local TEAEs (Excluding Infections)
TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Number of Participants with local TEAEs (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Local TEAEs (Excluding Infections) | 11 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Local TEAEs (Excluding Infections) | 3 Participants |
Secondary
Safety: Number of Participants With Systemic Adverse Reaction (Excluding Infections)
Adverse reaction was defined as any TEAE that meets any of the following criteria: 1) A TEAE considered by either the investigator and/or the sponsor to be possibly or probably related to IP administration, or; 2) A TEAE that begins during infusion of IP or within 72 hours following the end of IP infusion, or; 3) A TEAE for which causality assessment is missing or indeterminate. Number of participants with systemic adverse reaction (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Systemic Adverse Reaction (Excluding Infections) | 3 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Systemic Adverse Reaction (Excluding Infections) | 1 Participants |
Secondary
Safety: Number of Participants With Systemic TEAEs (Excluding Infections)
TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. Number of participants with systemic TEAEs (excluding infections) was reported..
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HyQvia New Starters | Safety: Number of Participants With Systemic TEAEs (Excluding Infections) | 15 Participants |
| HyQvia Pre-treated | Safety: Number of Participants With Systemic TEAEs (Excluding Infections) | 10 Participants |
Secondary
Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2
Percentage of participants who achieved a treatment interval of three or four weeks in Epoch 2 was reported.
Time frame: Up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| HyQvia New Starters | Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 | Every 3 weeks treatment interval | 39.1 Percentage of participants |
| HyQvia New Starters | Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 | Every 4 weeks treatment interval | 60.9 Percentage of participants |
| HyQvia Pre-treated | Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 | Every 3 weeks treatment interval | 15.8 Percentage of participants |
| HyQvia Pre-treated | Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 | Every 4 weeks treatment interval | 84.2 Percentage of participants |
Secondary
Safety: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 up to 12 Months
Percentage of participants who maintained a treatment interval of three or four weeks in Epoch 2 up to 12 months was reported.
Time frame: Up to 12 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 up to 12 Months | 87.0 Percentage of participants |
| HyQvia Pre-treated | Safety: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 up to 12 Months | 78.9 Percentage of participants |
Secondary
Safety: Rate of Any Adverse Reaction Per Infusion (Excluding Infections)
Rate of all adverse reactions per infusion was calculated as number of adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of any adverse reactions per infusion (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of Any Adverse Reaction Per Infusion (Excluding Infections) | 0.091 Adverse reaction event/Infusion |
| HyQvia Pre-treated | Safety: Rate of Any Adverse Reaction Per Infusion (Excluding Infections) | 0.021 Adverse reaction event/Infusion |
Secondary
Safety: Rate of Any Related (Causally) and/or Temporally Associated TEAEs Per Infusion (Excluding Infections)
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 start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of Any Related (Causally) and/or Temporally Associated TEAEs Per Infusion (Excluding Infections) | 0.112 Related Temporally TEAEs/Infusion |
| HyQvia Pre-treated | Safety: Rate of Any Related (Causally) and/or Temporally Associated TEAEs Per Infusion (Excluding Infections) | 0.033 Related Temporally TEAEs/Infusion |
Secondary
Safety: Rate of Any Temporally Associated TEAEs Per Infusion (Excluding Infections)
Rate of any temporally associated TEAEs per infusion was calculated as number of temporally associated adverse events/total number of infusions administered to participants in the analysis set. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. Rate of any temporally associated TEAEs per infusion (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of Any Temporally Associated TEAEs Per Infusion (Excluding Infections) | 0.106 Temporally associated TEAEs/Infusion |
| HyQvia Pre-treated | Safety: Rate of Any Temporally Associated TEAEs Per Infusion (Excluding Infections) | 0.027 Temporally associated TEAEs/Infusion |
Secondary
Safety: Rate of Local Adverse Reaction Per Infusion (Excluding Infections)
Rate of local adverse reaction per infusion was calculated as number of local adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of local adverse reactions per infusion (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of Local Adverse Reaction Per Infusion (Excluding Infections) | 0.080 Number of Local AR events/Infusion |
| HyQvia Pre-treated | Safety: Rate of Local Adverse Reaction Per Infusion (Excluding Infections) | 0.009 Number of Local AR events/Infusion |
Secondary
Safety: Rate of Local TEAEs Per Infusion (Excluding Infections)
Rate of local TEAEs per infusion was calculated as number of local adverse events/total number of infusions administered to participants in the analysis set. Only events are included which start prior to participants start date of non-response. Rate of local TEAEs per infusion (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of Local TEAEs Per Infusion (Excluding Infections) | 0.082 Number of local TEAEs/Infusion |
| HyQvia Pre-treated | Safety: Rate of Local TEAEs Per Infusion (Excluding Infections) | 0.009 Number of local TEAEs/Infusion |
Secondary
Safety: Rate of Serious TEAEs Per Infusion (Excluding Infections)
Rate of serious TEAEs per infusion was calculated as number of serious adverse events/total number of infusions administered to participants in the analysis set. Rate of serious TEAEs per infusion (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of Serious TEAEs Per Infusion (Excluding Infections) | 0 Number of serious TEAEs/Infusion |
| HyQvia Pre-treated | Safety: Rate of Serious TEAEs Per Infusion (Excluding Infections) | 0.012 Number of serious TEAEs/Infusion |
Secondary
Safety: Rate of Systemic Adverse Reaction Per Infusion (Excluding Infections)
Rate of Systemic adverse reactions per infusion was calculated as number of systemic adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of systemic adverse reactions per infusion (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of Systemic Adverse Reaction Per Infusion (Excluding Infections) | 0.011 Number of systemic AR events/Infusion |
| HyQvia Pre-treated | Safety: Rate of Systemic Adverse Reaction Per Infusion (Excluding Infections) | 0.012 Number of systemic AR events/Infusion |
Secondary
Safety: Rate of Systemic TEAEs Per Infusion (Excluding Infections)
Rate of systemic TEAEs per infusion was calculated as number of systemic adverse events/total number of infusions administered to participants in the analysis set. Rate of systemic TEAEs per infusion was assessed based on events per infusion.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of Systemic TEAEs Per Infusion (Excluding Infections) | 0.138 Number of systemic TEAEs/Infusion |
| HyQvia Pre-treated | Safety: Rate of Systemic TEAEs Per Infusion (Excluding Infections) | 0.142 Number of systemic TEAEs/Infusion |
Secondary
Safety: Rate of TEAEs Per Infusion (Excluding Infections)
Rate of TEAEs per infusion was calculated as number of adverse events/total number of infusions administered to participants in the analysis set. Rate of TEAEs per infusion (excluding infections) was reported.
Time frame: From start of study drug administration up to 20 months
Population: Safety analysis set included all participants in the full analysis set (enrolled set) who received at least one dose of HyQvia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HyQvia New Starters | Safety: Rate of TEAEs Per Infusion (Excluding Infections) | 0.220 Number of TEAEs/Infusion |
| HyQvia Pre-treated | Safety: Rate of TEAEs Per Infusion (Excluding Infections) | 0.151 Number of TEAEs/Infusion |