Clinical Trial Results:
Efficacy, Safety, Tolerability, Immunogenicity and Pharmacokinetic Evaluation of HYQVIA in Pediatric Subjects with Primary Immunodeficiency Diseases
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Summary
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EudraCT number |
2022-003501-29 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
20 Jul 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Feb 2023
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First version publication date |
07 Feb 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
161503
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03277313 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Takeda
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Sponsor organisation address |
95 Hayden Avenue, Lexington, United States, MA 02421
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Public contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Scientific contact |
Study Director, Takeda, TrialDisclosures@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Jul 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Jul 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of this study was to assess the efficacy of HYQVIA treatment in pediatric participants with primary immunodeficiency disease (PIDD) who received prior intravenous (IV) or subcutaneous (SC) immunoglobulin therapy before enrollment into the study.
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Protection of trial subjects |
All study participants and/or their legally authorised representative had to sign an informed consent form (ICF) before entering into the study. Assent was also obtained from the participant as applicable.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Sep 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 44
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Worldwide total number of subjects |
44
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
32
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Adolescents (12-17 years) |
12
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants took part in the study at 19 investigative sites in the United States from 25 September 2017 to 20 July 2022. Pediatric participants with a diagnosis of primary immunodeficiency diseases (PIDD) were enrolled in this study. | ||||||||||||||||
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Pre-assignment
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Screening details |
Pediatric participants who received IV or non-HYQVIA SC immunoglobulin therapy prior to enrollment received ramp-up doses of HYQVIA in Epoch 1 and at 3- or 4-week intervals in Epoch 2. Epoch 3 was planned for safety follow-up if needed, however no participants continued in Epoch 3. Data is reported only for Epoch 1 and 2. | ||||||||||||||||
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Period 1
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Period 1 title |
Epoch 1 (Six-week Ramp-up Period)
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Is this the baseline period? |
Yes | ||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Epoch 1 | ||||||||||||||||
Arm description |
Pediatric participants with PIDD who were on IV or non-HYQVIA SC treatment with immunoglobulin were enrolled and treated with HYQVIA SC with a dose or interval ramp-up period of up to six weeks. HYQVIA dose was planned to be equivalent to 100% (± 5%) of pre-study treatment. Dose frequency was one treatment interval of one week, then one treatment interval of two weeks for participants who were planned to be treated every three weeks, and one more treatment interval of three weeks for participants who were planned to be treated every four weeks. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
HYQVIA
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Investigational medicinal product code |
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Other name |
IGI 10% with rHuPH20
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use, Subcutaneous use
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Dosage and administration details |
Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (IGI, 10% with rHuPH20)
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Period 2
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Period 2 title |
Epoch 2 (36 Months After Epoch 1)
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Is this the baseline period? |
No | ||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||
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Arms
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Arm title
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Epoch 2 | ||||||||||||||||
Arm description |
Epoch 1 was followed by Epoch 2 with HYQVIA treatment infusions given once every 3 or 4 weeks, depending on the participant’s previous IV dosing schedule (for IV pretreated participants) and at the discretion of the investigator and participant (for SC-pretreated participants) up to approximately 36 months. | ||||||||||||||||
Arm type |
Experimental | ||||||||||||||||
Investigational medicinal product name |
HYQVIA
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Investigational medicinal product code |
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Other name |
IGI 10% with rHuPH20
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use, Subcutaneous use
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Dosage and administration details |
Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (IGI, 10% with rHuPH20)
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Baseline characteristics reporting groups
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Reporting group title |
Epoch 1
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Reporting group description |
Pediatric participants with PIDD who were on IV or non-HYQVIA SC treatment with immunoglobulin were enrolled and treated with HYQVIA SC with a dose or interval ramp-up period of up to six weeks. HYQVIA dose was planned to be equivalent to 100% (± 5%) of pre-study treatment. Dose frequency was one treatment interval of one week, then one treatment interval of two weeks for participants who were planned to be treated every three weeks, and one more treatment interval of three weeks for participants who were planned to be treated every four weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Epoch 1 + Epoch 2
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Pediatric participants with PIDD who were on IV or non-HYQVIA SC treatment with immunoglobulin were enrolled and treated with HYQVIA SC with a dose or interval ramp-up period of up to six weeks. HYQVIA dose was planned to be equivalent to 100% (± 5%) of pre-study treatment. Dose frequency was one treatment interval of one week, then one treatment interval of two weeks for participants who were planned to be treated every three weeks, and one more treatment interval of three weeks for participants who were planned to be treated every four weeks. Epoch 1 was followed by Epoch 2 with HYQVIA treatment infusions given once every 3 or 4 weeks, depending on the participant’s previous IV dosing schedule (for IV pretreated participants) and at the discretion of the investigator and participant (for SC-pretreated participants) up to approximately 36 months.
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End points reporting groups
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Reporting group title |
Epoch 1
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Reporting group description |
Pediatric participants with PIDD who were on IV or non-HYQVIA SC treatment with immunoglobulin were enrolled and treated with HYQVIA SC with a dose or interval ramp-up period of up to six weeks. HYQVIA dose was planned to be equivalent to 100% (± 5%) of pre-study treatment. Dose frequency was one treatment interval of one week, then one treatment interval of two weeks for participants who were planned to be treated every three weeks, and one more treatment interval of three weeks for participants who were planned to be treated every four weeks. | ||
Reporting group title |
Epoch 2
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Reporting group description |
Epoch 1 was followed by Epoch 2 with HYQVIA treatment infusions given once every 3 or 4 weeks, depending on the participant’s previous IV dosing schedule (for IV pretreated participants) and at the discretion of the investigator and participant (for SC-pretreated participants) up to approximately 36 months. | ||
Subject analysis set title |
Epoch 1 + Epoch 2
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Pediatric participants with PIDD who were on IV or non-HYQVIA SC treatment with immunoglobulin were enrolled and treated with HYQVIA SC with a dose or interval ramp-up period of up to six weeks. HYQVIA dose was planned to be equivalent to 100% (± 5%) of pre-study treatment. Dose frequency was one treatment interval of one week, then one treatment interval of two weeks for participants who were planned to be treated every three weeks, and one more treatment interval of three weeks for participants who were planned to be treated every four weeks. Epoch 1 was followed by Epoch 2 with HYQVIA treatment infusions given once every 3 or 4 weeks, depending on the participant’s previous IV dosing schedule (for IV pretreated participants) and at the discretion of the investigator and participant (for SC-pretreated participants) up to approximately 36 months.
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End point title |
Rate Represented as Mean Number of Acute Serious Bacterial Infections (ASBI) per Participant-year [1] | ||||||||
End point description |
The rate of ASBI was defined as the mean number of ASBI per participant-year based on the United States (U.S.) Food and drugs Administration (FDA) guidance for industry to support marketing of human immune globulin intravenous (IGIV) as replacement therapy for primary humoral immunodeficiency and the European Medicines Agency (EMA) guideline on the clinical investigation of human normal immunoglobulin for SC and /or intramuscular administration. ASBI included bacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess, diagnosed according to the Diagnostic Criteria for Acute Serious Bacterial Infections. Full Analysis Set (FAS) included all participants who provided informed consent, and met enrollment eligibility.
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End point type |
Primary
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End point timeframe |
From first dose of study drug up to end of Study Epoch 2 (up to approximately 37.2 months)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical comparison was performed between arms (as this is a single arm study), the ASBI rate was compared to a fixed threshold (1.0) defined by an FDA Guideline. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Rate Represented as Mean Number of All Infections per Participant-year | ||||||||
End point description |
The rate of all infections was defined as the mean number of all infections per participant-year. Number of all infections was calculated as number of infections per participant-year. FAS included all participants who provided informed consent, and met enrollment eligibility.
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End point type |
Secondary
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End point timeframe |
From first dose of study drug up to end of Study Epoch 2 (up to approximately 37.2 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
FAS=all participants who provided informed consent, and met enrollment eligibility. Only FAS participants in Epoch 2 were analysed for this outcome measure. Number of subjects analysed=number of participants with data available for analyses. Number analysed(n)=number of participants with data available for analysis at specified timepoint. 9999=Standard deviation (SD) was not estimable for 1 participant. 99999=Data was not estimable for 0 participants.
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End point type |
Secondary
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End point timeframe |
Study Epoch 2, Year 1: Months 0, 6, and 12; Year 2: Months 18, 24 and 36
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorised as Clostridium Tetani Toxoid and Hepatitis B Virus | ||||||||||||||||||||
End point description |
FAS=all participants who provided informed consent, and met enrollment eligibility. Only FAS participants in Epoch 2 were analysed for this outcome measure. Number of subjects analysed=number of participants with data available for analyses. Number analysed=number of participants with data available for analysis at specified timepoint. IU/mL international units per milliliters. CTT=Clostridium Tetani Toxoid. Ab=Antibody. HBV=Hepatitis B Virus.
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End point type |
Secondary
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End point timeframe |
Study Epoch 2, Year 2: Months 6, 24, and 36
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen Haemophilus Influenzae B | ||||||||||||||
End point description |
FAS=all participants who provided informed consent, and met enrollment eligibility. Only FAS participants in Epoch 2 were analysed for this outcome measure. Number of subjects analysed=number of participants with data available for analyses. Number analysed=number of participants with data available for analysis at specified timepoint.
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End point type |
Secondary
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End point timeframe |
Study Epoch 2, Year 2: Months 6, 24, and 36
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Epoch 2: Area Under the Curve Normalised for Week (AUCweek) | ||||||||
End point description |
Pharmacokinetic analysis set (PKAS) included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Number of subjects analysed is the number of participants with data available for analyses. As pre-specified in statistical analysis plan (SAP), this outcome measure was planned only for Epoch 2.
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End point type |
Secondary
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End point timeframe |
Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Epoch 2: Area Under the Curve Over the Infusion Interval (AUCTau) | ||||||||
End point description |
PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Number of subjects analysed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
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End point type |
Secondary
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End point timeframe |
Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Epoch 2: Apparent Clearance (CL/F) | ||||||||
End point description |
PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Number of subjects analysed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
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End point type |
Secondary
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End point timeframe |
Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Epoch 2: Minimum Concentration (Cmin) | ||||||||
End point description |
PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Number of subjects analysed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
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End point type |
Secondary
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End point timeframe |
Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Epoch 2: Maximum Concentration (Cmax) | ||||||||
End point description |
PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Number of subjects analysed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
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End point type |
Secondary
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End point timeframe |
Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Epoch 2: Time to Maximum Concentration (Tmax) | ||||||||
End point description |
PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Number of subjects analysed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
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End point type |
Secondary
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End point timeframe |
Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Epoch 2: Terminal Half-life (T 1/2) | ||||||||
End point description |
PKAS included all participants in the Safety Analysis Set who have at least 1 evaluable post-dose concentration data for PK assessments without major protocol deviations or events affecting the PK results. Number of subjects analysed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
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End point type |
Secondary
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End point timeframe |
Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Serious Adverse Events (SAEs) Excluding Infections, Related and not Related | |||||||||||||||
End point description |
An SAE is defined as an untoward medical occurrence that at any dose is fatal, life-threatening, requires inpatient hospitalisation or results in prolongation of an existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event. Number of participants who experienced SAEs, related or not related, was reported. Safety Analysis Set (SAS) included all participants who received at least one dose of HyQvia.
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End point type |
Secondary
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End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Rate of SAEs Excluding Infections, Related and not Related, per Infusion | ||||||||||||||||||
End point description |
Rate of SAEs per infusion was calculated as number of serious adverse events/total number of infusions administered to participants in the analysis set. Rate of SAEs per infusion (excluding infections) was reported. SAS included all participants who received at least one dose of HyQvia.
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End point type |
Secondary
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End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Participants With all Treatment Emergent Adverse Events (TEAEs) Excluding Infections, Related and not Related | |||||||||||||||
End point description |
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced TEAEs, related or not related, was reported. SAS included all participants who received at least one dose of HyQvia.
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End point type |
Secondary
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End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Rate of all TEAEs Excluding Infections, Related and not Related, per Infusion | ||||||||||||||||||
End point description |
Rate of all TEAEs per infusion was calculated as number of any adverse reaction events/total number of infusions administered to participants in the analysis set. Rate of any adverse reactions per infusion (excluding infections) was reported. SAS included all participants who received at least one dose of HyQvia.
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End point type |
Secondary
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End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of Participants With Local TEAEs Excluding Infections, Related and not Related | |||||||||||||||
End point description |
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced local TEAEs, related or not related, was reported. SAS included all participants who received at least one dose of HyQvia.
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End point type |
Secondary
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End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Rate of Local TEAEs Excluding Infections, Related and not Related, per Infusion | ||||||||||||||||||
End point description |
Rate of local TEAEs per infusion was calculated as number of local TEAEs/total number of infusions administered to participants in the analysis set. Rate of local TEAEs per infusion (excluding infections) was reported. SAS included all participants who received at least one dose of HyQvia.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
||||||||||||||||
End point title |
Number of Participants With Systemic TEAEs Excluding Infections, Related and not Related | |||||||||||||||
End point description |
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced systemic TEAEs, related or not related, was reported. SAS included all participants who received at least one dose of HyQvia.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
|||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
|||||||||||||||||||
End point title |
Rate of Systemic TEAEs Excluding Infections, Related and not Related, per Infusion | ||||||||||||||||||
End point description |
Rate of systemic TEAEs per infusion was calculated as number of systemic TEAEs/total number of infusions administered to participants in the analysis set. Rate of systemic TEAEs per infusion (excluding infections) was reported. SAS included all participants who received at least one dose of HyQvia.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||
End point title |
Rate of all Temporally Associated TEAEs Excluding Infections per Infusion | ||||||||||||
End point description |
Rate of all temporally associated TEAEs per infusion was calculated as number of all temporally associated TEAEs/total number of infusions administered to participants in the analysis set. Rate of all temporally associated TEAEs per infusion (excluding infections) was reported. SAS included all participants who received at least one dose of HyQvia.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From beginning of infusion up to 72 hours post infusion
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||
End point title |
Number of Participants With all Temporally Associated TEAEs Excluding Infections | |||||||||
End point description |
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants who experienced all temporally associated TEAEs, related or not related, was reported. SAS included all participants who received at least one dose of HyQvia.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From beginning of infusion up to 72 hours post infusion
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
||||||||||
End point title |
Number of Participants With all Related (Causally) and/or Temporally Associated TEAEs Excluding Infections | |||||||||
End point description |
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Number of participants with any related (causally) and/or temporally associated TEAEs (excluding infections) was reported. Temporally-associated TEAEs were defined as TEAEs which begin during infusion of IP or within 72 hours following the end of IP infusion. SAS included all participants who received at least one dose of HyQvia.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From beginning of infusion up to 72 hours post infusion
|
|||||||||
|
||||||||||
| No statistical analyses for this end point | ||||||||||
|
|||||||||||||
End point title |
Rate of Participants With all Related (Causally) and/or Temporally Associated TEAEs Excluding Infections per Infusion | ||||||||||||
End point 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. SAS included all participants who received at least one dose of HyQvia.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From beginning of infusion up to 72 hours post infusion
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||||||
End point title |
Percentage of Participants With any TEAEs Excluding Infections | ||||||||||||
End point description |
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. Percentages are rounded off to whole number at the nearest decimal. SAS included all participants who received at least one dose of HyQvia.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Percentage of Participants who Developed Positive Titer (≥160) of Binding or Neutralising Antibodies to rHuPH20 | ||||||||
End point description |
Percentage of participants who developed positive titer (rHuPH20 titer ≥160) of binding antibodies to rHuPH20 was reported. Neutralising antibodies were only tested if the participant had a titer of ≥160 of binding antibodies. Participants with multiple assessments of titer of ≥160 of binding antibodies are counted only once. Percentages are rounded off to whole number at the nearest decimal. FAS included all participants who provided informed consent, and met enrollment eligibility.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||
End point title |
Number of Participants who Developed Positive Titer (≥160) of Binding or Neutralising Antibodies to rHuPH20 | ||||||
End point description |
Number of participants who developed positive titer (rHuPH20 titer ≥160) of binding antibodies to rHuPH20 was reported. Neutralising antibodies were only tested if the participant had a titer of ≥160 of binding antibodies. Participants with multiple assessments of titer of ≥160 of binding antibodies are counted only once. FAS included all participants who provided informed consent, and met enrollment eligibility.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||
End point title |
Epoch 2: Number of Infusion Sites (Needle Sticks) per Infusion | ||||||||
End point description |
SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Study Epoch 2: Up to 36 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Epoch 2: Number of Infusions per Month | ||||||||
End point description |
SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Study Epoch 2: Up to 36 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Epoch 2: Number of Infusion Sites (Needle Sticks) per Month | ||||||||
End point description |
SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Study Epoch 2: Up to 36 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Epoch 2: Maximum Infusion Rate per Site | ||||||||
End point description |
HYQVIA treatment infusions in Epoch 2 were given at a rate of 10 milliliters per hour per site (mL/h/site) to 160 ml/h/site (body weight [BW] of <40 kg) and 10 mL/h/site to 300 mL/h/site (BW of ≥40 kg). SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2. mL/h/site= milliliters per hour per site.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Study Epoch 2: Up to 36 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Epoch 2: Duration of Infusion | ||||||||
End point description |
Duration of infusion is the time from the start of rHuPH20 infusion until the stop time of immunoglobulin infusion. SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Study Epoch 2: Up to 36 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Epoch 2: Infusion Volume per Site | ||||||||
End point description |
SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Study Epoch 2: Up to 36 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||
End point title |
Epoch 2: Infusions Which Were Discontinued, Slowed, or Interrupted due to an AE | ||||||||||||||
End point description |
SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Study Epoch 2: Up to 36 months
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||||
End point title |
Epoch 2: Percentage of Infusions Which Were Discontinued, Slowed, or Interrupted due to an AE | ||||||||||||||
End point description |
Percentages are rounded off to whole number at the nearest decimal. SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
Study Epoch 2: Up to 36 months
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||||
End point title |
Epoch 2: Percentage of Participants who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2 | ||||||||||||
End point description |
Percentages are rounded off to whole number at the nearest decimal. SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Study Epoch 2: Up to 36 months
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Epoch 1: Number of Weeks to Reach Final Dose Interval | ||||||||
End point description |
SAS included all participants who received at least one dose of HyQvia. Number of subjects analysed is the number of participants with data available for analyses. As pre-specified in SAP, this outcome measure was planned only for Epoch 1.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Epoch 1 (up to 6 weeks)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Epoch 2: Percentage of Participants who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 for 12 Months | ||||||||
End point description |
Percentages are rounded off to whole number at the nearest decimal. SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Study Epoch 2: Up to 12 months
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score | ||||||||||||||||||||||||||||||||||||||||
End point description |
Peds-QL=generic questionnaire developed,validated measuring HRQoL in pediatric population.4domains measured:physical,emotional,social,school functioning.Age groups:Toddler(2-4years[y]),Young child(5-7y),Child(8-12y),Teens(13-<18y).Depending on participant age,questionnaire completed by participant/ parent/caregiver as appropriate.Toddler group,PedsQL Generic Core Scale(GCS):21 items,using 5-point Likert scale(0-4);all other groups,PedsQL:23 items,3-point Likert scale(0,2,4)young child, 5-point Likert scale for child,teens groups.Scores were transformed on scale 0-100;0=100,1=75,2=50,3=25,4=0.Total score,domain scores calculated with higher scores indicating better health.End of Epoch2=participant's data for last epoch2 visit(not including participant discontinuing epoch1).SAS=participants receiving atleast 1dose of HyQvia.Number of subjects analysed=participants with data for analyses,n=participants with data at specified timepoint.CFB=Change From Baseline.C/T=completion/termination.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point title |
HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D=validated,self-administered assessment of overall health consisting of 5 dimensions(mobility,self-care,usual activities,pain/discomfort,anxiety/depression).Participants were asked to describe health state that day by choosing 1 of 3 responses reflecting levels of severity for 5 dimensions:no problems,some or moderate problems,extreme problems.Total score,domain scores calculated with higher scores indicating worsening health status.EQ-5D includes standard vertical 20cm visual analogue scale (VAS) for recording participant’s rating of current HRQoL state,ranging from 0-100,0 indicated worst imaginable health state,100 was best imaginable health state.End of Epoch2=participant's data for last epoch2 visit (not including participant discontinuing in epoch1).SAS=participants who received at least one dose of HyQvia.Number of subjects analysed=participants with data available for analyses.n=participants with data available for analysis at specified timepoint.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score | ||||||||||||||||||||||||||||||||||||||||
End point description |
The LQI is a validated questionnaire assessing participant perceptions of their HRQoL and their treatment specifically among participants who use IgG therapy. This questionnaire covers 4 domains: treatment interferences, therapy-related problems, therapy setting, and treatment costs. The LQI domains are scored from 0 to 100, with higher scores associated with better IgG treatment satisfaction. End of Epoch 2 summarises all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1). SAS included all participants who received at least one dose of HyQvia. Number of subjects analysed is the number of participants with data available for analyses. Number analysed (n) is the number of participants with data available for analysis at a specified timepoint.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
End point title |
Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score | ||||||||||||||||||||||||||||||||
End point description |
The TSQM-9 is a 9-item, validated, self-administered instrument to assess subject satisfaction with medication, which assesses 3 domains: effectiveness, convenience, and global satisfaction. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction. End of Epoch 2 summarises all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1). SAS included all participants who received at least one dose of HyQvia. Number of subjects analysed is the number of participants with data available for analyses. Number analysed (n) is the number of participants with data available for analysis at a specified timepoint.
|
||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||
End point timeframe |
Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
|
||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
|
|||||||||||||
End point title |
Treatment Preference and Satisfaction: Number of Participants Who Completed Treatment Preference Questionnaire | ||||||||||||
End point description |
The treatment preference questionnaire, internally developed by the study sponsor, is a self-administered, non-validated scale assessing participant preference for various attributes of immunoglobulin G (IgG) therapy.End of Epoch 2 summarises all participant's data for their last epoch 2 visit (so not including the participant that discontinued in epoch 1). SAS included all participants who received at least one dose of HyQvia. As pre-specified in SAP, this outcome measure was planned only for Epoch 2.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Study Epoch 2: Up to Month 36
|
||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
|||||||||
End point title |
Health Resource Utilisation: Days not Able to go to School or Work, or to Perform Normal Daily Activities | ||||||||
End point description |
Days not able to go to school or work, or to perform normal daily activities due to infection or other illnesses were calculated as days not able to go to school or work, or to perform normal daily activities due to infection or other illnesses per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all subjects in the analysis set, divided by 365.25. SAS included all participants who received at least one dose of HyQvia.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Health Resource Utilisation: Days on Antibiotics | ||||||||
End point description |
Days on antibiotics were calculated as days on antibiotics per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all subjects in the analysis set, divided by 365.25. SAS included all participants who received at least one dose of HyQvia.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Health Resource Utilisation: Number of Hospitalisations | ||||||||
End point description |
Number of hospitalisations, indication for the hospitalisation (infection or non-infection) were calculated as number of hospitalisations, indication for the hospitalisation (infection or non-infection) per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all subjects in the analysis set, divided by 365.25. SAS included all participants who received at least one dose of HyQvia.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Health Resource Utilisation: Number of Days Hospitalised per Participant-Year | ||||||||
End point description |
Number of days hospitalised were calculated as number of days hospitalised per participant-year. Per participant-years = number or days reported / total number of years of study duration, i.e., the sum of study duration for all subjects in the analysis set, divided by 365.25. SAS included all participants who received at least one dose of HyQvia.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From first dose of study drug up to EOS (up to 4 years 9 months)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
At each visit the investigator had to document any occurrence of AE and abnormal laboratory findings. Any event spontaneously reported by the participant via the participant diary or observed by the investigator was recorded, irrespective of the relation to study treatment. SAS included all participants who received at least one dose of HYQVIA.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.0
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Reporting groups
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Reporting group title |
Epoch 2
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Reporting group description |
Epoch 1 was followed by Epoch 2 with HYQVIA treatment infusions given once every 3 or 4 weeks, depending on the participant’s previous IV dosing schedule (for IV pretreated participants) and at the discretion of the investigator and participant (for SC-pretreated participants) up to approximately 36 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Epoch 1
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Reporting group description |
Pediatric participants with PIDD who were on IV or non-HYQVIA SC treatment with immunoglobulin were enrolled and treated with HYQVIA SC with a dose or interval ramp-up period of up to six weeks. HYQVIA dose was planned to be equivalent to 100% (± 5%) of pre-study treatment. Dose frequency was one treatment interval of one week, then one treatment interval of two weeks for participants who were planned to be treated every three weeks, and one more treatment interval of three weeks for participants who were planned to be treated every four weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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20 Jul 2017 |
Following changes were implemented with Protocol Amendment 1: -Included word “efficacy” in study title, short study title, and wherever applicable. -Clarified that latest approved version of prescribing Information for United States (US) would be applicable. -Updated study status from planned to ongoing. -Updated study purpose and objectives. -Revised and rearranged secondary and tertiary objectives. -Provided information on testing and characterisation of neutralising anti-rHuPH20. -Updated overall study design. -Clarified time point and location of study completion visit. -Updated blood sample collection information for PK assessments. -Updated study outcome measures. -Revised stopping rules. -Moved GAMMAGARD LIQUID administration instructions to applicable section of protocol. -Provided additional guidance on administration of HYQVIA. -Provided additional clarification that treatment with GAMMAGARD LIQUID will follow guidance of product information and site´s standard of care. -Widened range of potential source data documents. -Update text to define exclusion criterion. -Clarified definition of “enrollment” for informed consent. -Updated text to define screening and clarified screening/re-screening procedures and time limit. -Provided additional information regarding timepoints of administration of QoL questionnaires and treatment preference and satisfaction assessments. -Removed redundant information about PK assessments. -Reflected an operational change. -Clarified of data collection method to match secondary outcome measures, and to add LQI to allow for collection of additional QoL data. -Limited investigator´s responsibility to report SAEs after study completion. -Deleted requirement of a Non-Medical Complaints (NMC) form, and updated term used for safety monitoring committee. -Updated clinical laboratory sections (hematology, chemistry, anti-rHuPH20 antibodies) and related tables. -Updated statistical section. -Updated schedule of assessments. |
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24 Mar 2019 |
Following changes were implemented with Protocol Amendment 2: -Clarified that the safety follow-up and antibody testing were to continue for 1 year, not less, for all participants who were switched to Epoch 3. -Allowed shorter infusion intervals (e.g., 2 weeks) in Epoch 2 to provide increased flexibility for pediatric participants. -Clarified that for pediatric participants, the full vial of rHuPH20 will not always be needed. -Clarified when rHuPH20 dose adjustments were required. -Clarified the study procedures that were to be performed at scheduled site visits and those that were to be performed outside of scheduled site visits. The schedule of study procedures and assessments was also updated accordingly. -Clarified that blood and urine collection were to occur pre-infusion but may be performed outside the specified time to accommodate the needs of young children. -Confirmed the IgG trough level at study entry without additional blood sampling for the pediatric participants. The clinical laboratory assessments tables were updated to better distribute the blood samples and ensure a baseline IgG trough level and IgG subclasses samples were taken. -Included two additional domains (a Life Quality Index domain and a Global Satisfaction domain) in the HRQoL statistical hypothesis testing. -Included additional descriptive statistics for the healthcare resource utilisation assessments. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
