Clinical trial NCT03116347: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Primary Immunodeficiency Diseases (PID)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxalta Innovations GmbH, now part of Shire
First posted: 2017-04-17
Enrollment: 42
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


Eligibility criteria: Inclusion Criteria:

1. Participant must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the International Union of Immunological Societies (IUIS) Scientific Committee 2015 prior to enrollment. The diagnosis must be confirmed by the sponsor´s Medical Director prior to first treatment with investigational product (IP) in the study.
2. Participant is at least two and below 18 years of age at the time of screening.
3. Participant has been receiving a consistent dose of Immunoglobulin G (IgG), administered in compliance with the respective product information for a period of at least three months prior to screening. The average minimum pre-study dose over that interval was equivalent to 300 mg/kg body weight (BW)/four weeks and a maximum dose equivalent to 1000 mg/kg BW/4 weeks.
4. Participant has a serum trough level of IgG \> 5 g/L at screening.
5. If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
6. Participant /legally authorized representative is willing and able to comply with the requirements of the protocol.

Exclusion Criteria:

1. Participant has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2.
2. Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):

   1. Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) \>2.5 times the upper limit of normal (ULN) for the testing laboratory
   2. Persistent severe neutropenia (defined as an absolute neutrophil count \[ANC\] ≤ 500/mm\^3)
3. Participant has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site.
4. Participant has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following intravenous (IV) immunoglobulin, subcutaneous (SC) immunoglobulin, and/or Immune Serum Globulin (ISG) infusions.
5. Participant has severe immunoglobulin A (IgA) deficiency (\< 7.0 mg/dL) with known anti-IgA antibodies and a history of hypersensitivity. .
6. Participant has a known allergy to hyaluronidase.
7. Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.
8. Participant has a bleeding disorder or a platelet count \< 20,000/μL, or who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of SC therapy.
9. Participant has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator.
10. Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.
11. Participant is a family member or employee of the investigator.
12. If female, participant is pregnant or lactating at the time of enrollment.

Primary outcomes:
measure: Safety: Number of Participants With Any Severe Related Treatment-emergent Adverse Events (TEAEs) Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of Any Severe Related TEAEs Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Number of Participants With Any Related Serious TEAEs Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of Any Related Serious TEAEs Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
Secondary outcomes:
measure: Efficacy: Change From Baseline in Total Serum Trough Levels of Immunoglobulin G (IgG) at Month 12
timeFrame: Baseline, Month 12
measure: Efficacy: Change From Baseline in Serum Trough Levels of IgG Subclasses at Month 12
timeFrame: Baseline, Month 12
measure: Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Clostridium Tetani Toxoid IgG at Month 12
timeFrame: Baseline, Month 12
measure: Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Hepatitis B Virus (HBV) at Month 12
timeFrame: Baseline, Month 12
measure: Efficacy: Change From Baseline in Trough Levels of Specific Antibodies to Haemophilus Influenzae B IgG at Month 12
timeFrame: Baseline, Month 12
measure: Safety: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2
timeFrame: Up to 20 months
measure: Safety: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 up to 12 Months
timeFrame: Up to 12 months
measure: Safety: Number of Participants With Local TEAEs (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of Local TEAEs Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Number of Participants With Local Adverse Reaction (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of Local Adverse Reaction Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Number of Participants With Systemic TEAEs (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of Systemic TEAEs Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Number of Participants With Systemic Adverse Reaction (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of Systemic Adverse Reaction Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Number of Participants With Any TEAEs (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of TEAEs Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Number of Participants With Any Adverse Reactions (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of Any Adverse Reaction Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Number of Participants With Any Temporally Associated TEAEs (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of Any Temporally Associated TEAEs Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Number of Participants With Any Related (Causally) and/or Temporally Associated TEAEs (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of Any Related (Causally) and/or Temporally Associated TEAEs Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Number of Participants With Any Serious TEAEs (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Rate of Serious TEAEs Per Infusion (Excluding Infections)
timeFrame: From start of study drug administration up to 20 months
measure: Safety: Number of Participants Who Developed Positive Titer (>=160) of Binding or Neutralizing Antibodies to rHuPH20
timeFrame: From start of study drug administration up to 20 months
measure: Other Analysis: Number of Infusions Per Month
timeFrame: Up to 20 months
measure: Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Infusion
timeFrame: Up to 20 months
measure: Other Analysis: Number of Infusion Sites (Needle-Sticks) Per Month
timeFrame: Up to 20 months
measure: Other Analysis: Duration of Infusion
timeFrame: From start of study drug administration up to 20 months.
measure: Other Analysis: Maximum Infusion Rate Per Site
timeFrame: Up to 20 months
measure: Other Analysis: Infusion Volume Per Site
timeFrame: Up to 20 months
measure: Other Analysis: Number of Infusions That Were Interrupted or Stopped Due to an AE
timeFrame: Up to 20 months
measure: Other Analysis: Number of Weeks to Reach Final 3 or 4-week Dose Interval in Epoch 1
timeFrame: Up to 20 months
measure: Health Related Quality of Life (HR QoL): Change From Baseline in Pediatric Quality of Life Questionnaire (PedsQL)
timeFrame: Baseline up to 20 months
measure: HRQoL: Change From Baseline in EuroQoL (Quality of Life)-5 Dimensions (EQ-5D)
timeFrame: Baseline up to 20 months
measure: HR QoL: Change From Baseline in Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9)
timeFrame: Baseline up to 20 months
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno Odd. Detska klinika
city: Nový Hradec Králové
country: Czechia
facility: Fakultní nemocnice Hradec Králové
city: Prague
country: Czechia
facility: FN v Motole Interni klinika
city: København
country: Denmark
facility: Rigshospitalet
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin - Hôpital des Enfants
state: Gironde
city: Angers
country: France
facility: CHU Angers - Hôpital Hôtel Dieu
city: Lyon
country: France
facility: Hospices Civils de Lyon - Hôpitaux Est - IHOP
city: Athens
country: Greece
facility: Agia Sophia Children's Hospital
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki Ippokrateio
city: Thessaloniki
country: Greece
facility: General Hospital of Thessaloniki Papageorgiou
city: Budapest
country: Hungary
facility: United St. Istvan and St. Laszlo Hospital
city: Bratislava
country: Slovakia
facility: 1.Detská klinika
city: Martin
country: Slovakia
facility: Univerzitna Nemocnica Klinika detí a dorastu
city: Goteborg
country: Sweden
facility: Queen Silvia Children's Hospital
city: Lund
country: Sweden
facility: Dept. of Pediatric Oncology/Hematology/Immunology-Skånes Universitetssjukhus
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
state: Avon
city: Leeds
country: United Kingdom
facility: Leeds Children's Hospital
state: West Yorkshire
city: Belfast
country: United Kingdom
facility: Royal Victoria Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales Heath Park Clinical Research Facility
city: Newcastle upon Tyne
country: United Kingdom
facility: The Great North Children's Hospital Royal Victoria Infirmary
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: