Back to resultsPost-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric PIDD Subjects
Primary Purpose
Primary Immunodeficiency Diseases (PID)
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
HYQVIA
KIOVIG
Cuvitru
Sponsored by
About this trial
This is an interventional treatment trial for Primary Immunodeficiency Diseases (PID)
Eligibility Criteria
Inclusion Criteria:
- 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.
- Participant is at least two and below 18 years of age at the time of screening.
- 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.
- Participant has a serum trough level of IgG > 5 g/L at screening.
- 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.
- Participant /legally authorized representative is willing and able to comply with the requirements of the protocol.
Exclusion Criteria:
- 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.
Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
- Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) >2.5 times the upper limit of normal (ULN) for the testing laboratory
- Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] ≤ 500/mm^3)
- Participant has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site.
- 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.
- Participant has severe immunoglobulin A (IgA) deficiency (< 7.0 mg/dL) with known anti-IgA antibodies and a history of hypersensitivity. .
- Participant has a known allergy to hyaluronidase.
- Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
- 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.
- Participant has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator.
- 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.
- Participant is a family member or employee of the investigator.
- If female, participant is pregnant or lactating at the time of enrollment.
Sites / Locations
- Fakultni nemocnice Brno Odd. Detska klinika
- Fakultní nemocnice Hradec Králové
- FN v Motole Interni klinika
- Rigshospitalet
- Groupe Hospitalier Pellegrin - Hôpital des Enfants
- CHU Angers - Hôpital Hôtel Dieu
- Hospices Civils de Lyon - Hôpitaux Est - IHOP
- Agia Sophia Children's Hospital
- General Hospital of Thessaloniki Ippokrateio
- General Hospital of Thessaloniki Papageorgiou
- United St. Istvan and St. Laszlo Hospital
- 1.Detská klinika
- Univerzitna Nemocnica Klinika detí a dorastu
- Queen Silvia Children's Hospital
- Dept. of Pediatric Oncology/Hematology/Immunology-Skånes Universitetssjukhus
- Bristol Royal Hospital for Children
- Leeds Children's Hospital
- Royal Victoria Hospital
- University Hospital of Wales Heath Park Clinical Research Facility
- The Great North Children's Hospital Royal Victoria Infirmary
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
EPOCH 1
EPOCH 2
Epoch 3
Arm Description
Ramp up period for participants who were not treated with HyQvia prior to this study
Participants who were treated with HyQvia prior to this study, and those who completed the ramp up period (Epoch 1). After one year in Epoch 2, participants with anti-rHuPH20 antibody titer <160 at all time-points during the study will complete the study termination/completion visit at the next possible occasion. Participants with anti-rHuPH20 antibody titer >=160 during the study and/or at the last measurement will continue for an additional two years of HyQvia treatment and observation.
Safety follow-up for participants whose anti-rHuPH20 antibody titer was >= 160 during Epoch 1 or Epoch 2 and who experience either a related serious adverse event (SAE) or a related severe adverse event (AE)
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
Secondary Outcome Measures
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.
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.
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".
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.
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.
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.
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.
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.
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.
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.
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.
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..
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Analysis: Maximum Infusion Rate Per Site
Maximum infusion rate per site was reported.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT03116347
First Posted
April 12, 2017
Last Updated
April 13, 2022
Sponsor
Baxalta now part of Shire
Collaborators
Baxalta Innovations GmbH, now part of Shire
1. Study Identification
Unique Protocol Identification Number
NCT03116347
Brief Title
Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric PIDD Subjects
Official Title
Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric Subjects With Primary Immunodeficiency Diseases
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
May 30, 2017 (Actual)
Primary Completion Date
January 15, 2021 (Actual)
Study Completion Date
January 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire
Collaborators
Baxalta Innovations GmbH, now part of Shire
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immunodeficiency Diseases (PID)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EPOCH 1
Arm Type
Experimental
Arm Description
Ramp up period for participants who were not treated with HyQvia prior to this study
Arm Title
EPOCH 2
Arm Type
Experimental
Arm Description
Participants who were treated with HyQvia prior to this study, and those who completed the ramp up period (Epoch 1). After one year in Epoch 2, participants with anti-rHuPH20 antibody titer <160 at all time-points during the study will complete the study termination/completion visit at the next possible occasion. Participants with anti-rHuPH20 antibody titer >=160 during the study and/or at the last measurement will continue for an additional two years of HyQvia treatment and observation.
Arm Title
Epoch 3
Arm Type
Experimental
Arm Description
Safety follow-up for participants whose anti-rHuPH20 antibody titer was >= 160 during Epoch 1 or Epoch 2 and who experience either a related serious adverse event (SAE) or a related severe adverse event (AE)
Intervention Type
Biological
Intervention Name(s)
HYQVIA
Other Intervention Name(s)
IGI 10% with rHuPH20
Intervention Description
Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (IGI, 10% with rHuPH20)
Intervention Type
Biological
Intervention Name(s)
KIOVIG
Other Intervention Name(s)
IGIV 10%, IGI 10%
Intervention Description
100 mg/ml solution for Immune Globulin Intravenous Infusion
Intervention Type
Biological
Intervention Name(s)
Cuvitru
Other Intervention Name(s)
IGSC 20%, IGI 20%
Intervention Description
200 mg/ml solution for Immune Globulin Subcutaneous Injection
Primary Outcome Measure Information:
Title
Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections)
Description
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
Title
Safety: Rate of Any Severe Related TEAEs Per Infusion (Excluding Infections)
Description
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
Title
Safety: Number of Participants With Any Related Serious TEAEs Per Infusion (Excluding Infections)
Description
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
Title
Safety: Rate of Any Related Serious TEAEs Per Infusion (Excluding Infections)
Description
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
Secondary Outcome Measure Information:
Title
Efficacy: Change From Baseline in Total Serum Trough Levels of Immunoglobulin G (IgG) at Month 12
Description
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
Title
Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12
Description
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
Title
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Clostridium Tetani Toxoid IgG at Month 12
Description
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
Title
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Hepatitis B Virus (HBV) at Month 12
Description
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
Title
Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Haemophilus Influenzae B IgG at Month 12
Description
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
Title
Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2
Description
Percentage of participants who achieved a treatment interval of three or four weeks in Epoch 2 was reported.
Time Frame
Up to 20 months
Title
Safety: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 up to 12 Months
Description
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
Title
Safety: Number of Participants With Local TEAEs (Excluding Infections)
Description
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
Title
Safety: Rate of Local TEAEs Per Infusion (Excluding Infections)
Description
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
Title
Safety: Number of Participants With Local Adverse Reaction (Excluding Infections)
Description
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
Title
Safety: Rate of Local Adverse Reaction Per Infusion (Excluding Infections)
Description
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
Title
Safety: Number of Participants With Systemic TEAEs (Excluding Infections)
Description
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
Title
Safety: Rate of Systemic TEAEs Per Infusion (Excluding Infections)
Description
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
Title
Safety: Number of Participants With Systemic Adverse Reaction (Excluding Infections)
Description
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
Title
Safety: Rate of Systemic Adverse Reaction Per Infusion (Excluding Infections)
Description
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
Title
Safety: Number of Participants With Any TEAEs (Excluding Infections)
Description
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
Title
Safety: Rate of TEAEs Per Infusion (Excluding Infections)
Description
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
Title
Safety: Number of Participants With Any Adverse Reactions (Excluding Infections)
Description
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
Title
Safety: Rate of Any Adverse Reaction Per Infusion (Excluding Infections)
Description
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
Title
Safety: Number of Participants With Any Temporally Associated TEAEs (Excluding Infections)
Description
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
Title
Safety: Rate of Any Temporally Associated TEAEs Per Infusion (Excluding Infections)
Description
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
Title
Safety: Number of Participants With Any Related (Causally) and/or Temporally Associated TEAEs (Excluding Infections)
Description
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
Title
Safety: Rate of Any Related (Causally) and/or Temporally Associated TEAEs Per Infusion (Excluding Infections)
Description
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
Title
Safety: Number of Participants With Any Serious TEAEs (Excluding Infections)
Description
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
Title
Safety: Rate of Serious TEAEs Per Infusion (Excluding Infections)
Description
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
Title
Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20
Description
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
Title
Other Analysis: Number of Infusions Per Month
Description
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
Title
Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Infusion
Description
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
Title
Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Month
Description
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
Title
Other Analysis: Duration of Infusion
Description
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.
Title
Other Analysis: Maximum Infusion Rate Per Site
Description
Maximum infusion rate per site was reported.
Time Frame
Up to 20 months
Title
Other Analysis: Infusion Volume Per Site
Description
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
Title
Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE
Description
Number of infusions that were interrupted or Stopped due to an AE was reported.
Time Frame
Up to 20 months
Title
Other Analysis: Number of Weeks to Reach Final 3 or 4-week Dose Interval in Epoch 1
Description
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
Title
Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL)
Description
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
Title
HRQoL: Change From Baseline in EuroQoL (Quality of Life)-5 Dimensions (EQ-5D)
Description
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
Title
HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Participant is at least two and below 18 years of age at the time of screening.
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.
Participant has a serum trough level of IgG > 5 g/L at screening.
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.
Participant /legally authorized representative is willing and able to comply with the requirements of the protocol.
Exclusion Criteria:
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.
Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):
Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) >2.5 times the upper limit of normal (ULN) for the testing laboratory
Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] ≤ 500/mm^3)
Participant has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site.
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.
Participant has severe immunoglobulin A (IgA) deficiency (< 7.0 mg/dL) with known anti-IgA antibodies and a history of hypersensitivity. .
Participant has a known allergy to hyaluronidase.
Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
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.
Participant has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator.
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.
Participant is a family member or employee of the investigator.
If female, participant is pregnant or lactating at the time of enrollment.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Shire
Official's Role
Study Director
Facility Information:
Facility Name
Fakultni nemocnice Brno Odd. Detska klinika
City
Brno
ZIP/Postal Code
61300
Country
Czechia
Facility Name
Fakultní nemocnice Hradec Králové
City
Nový Hradec Králové
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
FN v Motole Interni klinika
City
Prague
ZIP/Postal Code
15006
Country
Czechia
Facility Name
Rigshospitalet
City
København
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Groupe Hospitalier Pellegrin - Hôpital des Enfants
City
Bordeaux
State/Province
Gironde
ZIP/Postal Code
33076
Country
France
Facility Name
CHU Angers - Hôpital Hôtel Dieu
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
Hospices Civils de Lyon - Hôpitaux Est - IHOP
City
Lyon
ZIP/Postal Code
69008
Country
France
Facility Name
Agia Sophia Children's Hospital
City
Athens
ZIP/Postal Code
115 27
Country
Greece
Facility Name
General Hospital of Thessaloniki Ippokrateio
City
Thessaloniki
ZIP/Postal Code
546 42
Country
Greece
Facility Name
General Hospital of Thessaloniki Papageorgiou
City
Thessaloniki
ZIP/Postal Code
564 03
Country
Greece
Facility Name
United St. Istvan and St. Laszlo Hospital
City
Budapest
ZIP/Postal Code
H-1097
Country
Hungary
Facility Name
1.Detská klinika
City
Bratislava
ZIP/Postal Code
83340
Country
Slovakia
Facility Name
Univerzitna Nemocnica Klinika detí a dorastu
City
Martin
ZIP/Postal Code
03659
Country
Slovakia
Facility Name
Queen Silvia Children's Hospital
City
Goteborg
ZIP/Postal Code
416 85
Country
Sweden
Facility Name
Dept. of Pediatric Oncology/Hematology/Immunology-Skånes Universitetssjukhus
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
Facility Name
Bristol Royal Hospital for Children
City
Bristol
State/Province
Avon
ZIP/Postal Code
BS2 8BJ
Country
United Kingdom
Facility Name
Leeds Children's Hospital
City
Leeds
State/Province
West Yorkshire
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Facility Name
Royal Victoria Hospital
City
Belfast
ZIP/Postal Code
BT1 6DW
Country
United Kingdom
Facility Name
University Hospital of Wales Heath Park Clinical Research Facility
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
The Great North Children's Hospital Royal Victoria Infirmary
City
Newcastle upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Learn more about this trial
Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric PIDD Subjects
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