Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric Subjects With Primary Immunodeficiency Diseases
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 42
- Locations
- 40
- Primary Endpoint
- Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections)
Study Overview
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)
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 2 Years to 17 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
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/
- •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.
Outcomes
Primary Outcomes
Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections)
Time Frame: From start of study drug administration up to 20 months
An Adverse Event (AE) was defined as any untoward medical occurrence in a participant administered an investigational product (IP) that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any severe related TEAEs (excluding infections) was reported.
Safety: Rate of Any Severe Related TEAEs Per Infusion (Excluding Infections)
Time Frame: From start of study drug administration up to 20 months
An AE was defined as any untoward medical occurrence in a participant administered an IP that does not necessarily have a causal relationship with the treatment. TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Severe related TEAEs rate per infusion was calculated as number of severe related TEAEs/total number of infusions administered to participants in the analysis set. Rate of any severe related TEAEs per infusion (excluding infections) was reported.
Safety: Number of Participants With Any Related Serious TEAEs Per Infusion (Excluding Infections)
Time Frame: From start of study drug administration up to 20 months
TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Number of participants with any related serious TEAEs per infusion (excluding infections) was reported.
Safety: Rate of Any Related Serious TEAEs Per Infusion (Excluding Infections)
Time Frame: From start of study drug administration up to 20 months
TEAEs were the AEs with onset after date-time of first dose of IP, or any medical condition present prior to the start of IP but increased in severity or relationship after date-time of first dose of IP. A serious TEAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in-patient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs that were recorded as "possibly related" or "probably related" to HYQVIA were considered HYQVIA-related adverse events. Rate of related serious TEAEs per infusion was calculated as number of related serious TEAEs/total number of infusions administered to participants in the analysis set. Rate of any related serious TEAEs per Infusion (excluding infections) was reported.
Secondary Outcomes
- Efficacy: Change From Baseline in Total Serum Trough Levels of Immunoglobulin G (IgG) at Month 12(Baseline, Month 12)
- Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12(Baseline, Month 12)
- Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Clostridium Tetani Toxoid IgG at Month 12(Baseline, Month 12)
- Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Hepatitis B Virus (HBV) at Month 12(Baseline, Month 12)
- Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Haemophilus Influenzae B IgG at Month 12(Baseline, Month 12)
- Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2(Up to 20 months)
- Safety: Number of Participants With Any TEAEs (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Rate of TEAEs Per Infusion (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 up to 12 Months(Up to 12 months)
- Safety: Number of Participants With Local TEAEs (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Rate of Local TEAEs Per Infusion (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Number of Participants With Local Adverse Reaction (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Rate of Local Adverse Reaction Per Infusion (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Number of Participants With Systemic TEAEs (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Rate of Systemic TEAEs Per Infusion (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Number of Participants With Systemic Adverse Reaction (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Rate of Systemic Adverse Reaction Per Infusion (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Number of Participants With Any Adverse Reactions (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Rate of Any Adverse Reaction Per Infusion (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Number of Participants With Any Temporally Associated TEAEs (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Rate of Any Temporally Associated TEAEs Per Infusion (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Number of Participants With Any Related (Causally) and/or Temporally Associated TEAEs (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Rate of Any Related (Causally) and/or Temporally Associated TEAEs Per Infusion (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Number of Participants With Any Serious TEAEs (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Rate of Serious TEAEs Per Infusion (Excluding Infections)(From start of study drug administration up to 20 months)
- Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20(From start of study drug administration up to 20 months)
- Other Analysis: Number of Infusions Per Month(Up to 20 months)
- Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Infusion(Up to 20 months)
- Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Month(Up to 20 months)
- Other Analysis: Duration of Infusion(From start of study drug administration up to 20 months.)
- Other Analysis: Maximum Infusion Rate Per Site(Up to 20 months)
- Other Analysis: Infusion Volume Per Site(Up to 20 months)
- Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE(Up to 20 months)
- Other Analysis: Number of Weeks to Reach Final 3 or 4-week Dose Interval in Epoch 1(Up to 20 months)
- Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL)(Baseline up to 20 months)
- HRQoL: Change From Baseline in EuroQoL (Quality of Life)-5 Dimensions (EQ-5D)(Baseline up to 20 months)
- HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9)(Baseline up to 20 months)