Clinical trial NCT03277313: Efficacy, Safety, Tolerability, Immunogenicity and Pharmacokinetic Evaluation of HYQVIA in Pediatric PIDD Subjects
Official title: Efficacy, Safety, Tolerability, Immunogenicity and Pharmacokinetic Evaluation of HYQVIA in Pediatric Subjects With Primary Immunodeficiency Diseases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Immunodeficiency Diseases (PID)
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxalta Innovations GmbH, now part of Shire
First posted: 2017-09-11
Enrollment: 44
Sex: ALL
Minimum age (years): 2
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of the study is to acquire additional data on efficacy, safety, tolerability, immunogenicity, pharmacokinetic (PK) and other parameters of HYQVIA in pediatric (age ≥ 2 to \<16 years) participants with primary immunodeficiency disease (PIDD).


Eligibility criteria: Inclusion Criteria:

1. Participant must have a documented diagnosis of a form of primary immunodeficiency (PI) involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the International Union of Immunological Societies (IUIS) Scientific Committee 2015 (Picard et al., 2015) prior to enrollment. The diagnosis must be confirmed by the sponsor´s Medical Director prior to first treatment with IP in the study.
2. Participant is at least two and below 16 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 BW / 4 weeks and a maximum dose equivalent to 1000 mg/kg body weight (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 aminotransferase (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 (less than 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 less than 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: Rate Represented as Mean Number of Acute Serious Bacterial Infections (ASBI) Per Participant-year
timeFrame: From first dose of study drug up to end of Study Epoch 2 (up to approximately 37.2 months)
Secondary outcomes:
measure: Rate Represented as Mean Number of All Infections Per Participant-year
timeFrame: From first dose of study drug up to end of Study Epoch 2 (up to approximately 37.2 months)
measure: Epoch 2: Trough Levels of Immunoglobulin G (IgG) Total and IgG Subclasses
timeFrame: Study Epoch 2, Year 1: Months 0, 6, and 12; Year 2: Months 18, 24 and 36
measure: Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogens Categorized as Clostridium Tetani Toxoid and Hepatitis B Virus
timeFrame: Study Epoch 2, Year 2: Months 6, 24, and 36
measure: Epoch 2: Trough Levels of Specific Antibodies to Clinically Relevant Pathogen Haemophilus Influenzae B
timeFrame: Study Epoch 2, Year 2: Months 6, 24, and 36
measure: Epoch 2: Area Under the Curve Normalized for Week (AUCweek)
timeFrame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
measure: Epoch 2: Area Under the Curve Over the Infusion Interval (AUCTau)
timeFrame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
measure: Epoch 2: Apparent Clearance (CL/F)
timeFrame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
measure: Epoch 2: Maximum Concentration (Cmax)
timeFrame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
measure: Epoch 2: Minimum Concentration (Cmin)
timeFrame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
measure: Epoch 2: Time to Maximum Concentration (Tmax)
timeFrame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
measure: Epoch 2: Terminal Half-life (T 1/2)
timeFrame: Study Epoch 2, Month 6: Day 0 pre-infusion, and at Days 2, 4, 10, 21 and 28 post-infusion
measure: Number of Participants With Serious Adverse Events (SAEs) Excluding Infections, Related and Not Related
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Rate of SAEs Excluding Infections, Related and Not Related, Per Infusion
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Number of Participants With All Treatment Emergent Adverse Events (TEAEs) Excluding Infections, Related and Not Related
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Rate of All TEAEs Excluding Infections, Related and Not Related, Per Infusion
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Number of Participants With Local TEAEs Excluding Infections, Related and Not Related
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Rate of Local TEAEs Excluding Infections, Related and Not Related, Per Infusion
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Number of Participants With Systemic TEAEs Excluding Infections, Related and Not Related
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Rate of Systemic TEAEs Excluding Infections, Related and Not Related, Per Infusion
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Number of Participants With All Temporally Associated TEAEs Excluding Infections
timeFrame: From beginning of infusion up to 72 hours post infusion
measure: Rate of All Temporally Associated TEAEs Excluding Infections Per Infusion
timeFrame: From beginning of infusion up to 72 hours post infusion
measure: Number of Participants With All Related (Causally) and/or Temporally Associated TEAEs Excluding Infections
timeFrame: From beginning of infusion up to 72 hours post infusion
measure: Rate of Participants With All Related (Causally) and/or Temporally Associated TEAEs Excluding Infections Per Infusion
timeFrame: From beginning of infusion up to 72 hours post infusion
measure: Percentage of Participants With Any TEAEs Excluding Infections
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Number of Participants Who Developed Positive Titer (≥160) of Binding or Neutralizing Antibodies to rHuPH20
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Percentage of Participants Who Developed Positive Titer (≥160) of Binding or Neutralizing Antibodies to rHuPH20
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Epoch 2: Number of Infusions Per Month
timeFrame: Study Epoch 2: Up to 36 months
measure: Epoch 2: Number of Infusion Sites (Needle Sticks) Per Infusion
timeFrame: Study Epoch 2: Up to 36 months
measure: Epoch 2: Number of Infusion Sites (Needle Sticks) Per Month
timeFrame: Study Epoch 2: Up to 36 months
measure: Epoch 2: Duration of Infusion
timeFrame: Study Epoch 2: Up to 36 months
measure: Epoch 2: Maximum Infusion Rate Per Site
timeFrame: Study Epoch 2: Up to 36 months
measure: Epoch 2: Infusion Volume Per Site
timeFrame: Study Epoch 2: Up to 36 months
measure: Epoch 2: Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE
timeFrame: Study Epoch 2: Up to 36 months
measure: Epoch 2: Percentage of Infusions Which Were Discontinued, Slowed, or Interrupted Due to an AE
timeFrame: Study Epoch 2: Up to 36 months
measure: Epoch 1: Number of Weeks to Reach Final Dose Interval
timeFrame: Epoch 1 (up to 6 weeks)
measure: Epoch 2: Percentage of Participants Who Achieved a Treatment Interval of Three or Four Weeks in Epoch 2
timeFrame: Study Epoch 2: Up to 36 months
measure: Epoch 2: Percentage of Participants Who Maintained a Treatment Interval of Three or Four Weeks in Epoch 2 for 12 Months
timeFrame: Study Epoch 2: Up to 12 months
measure: Health-related Quality of Life (HRQoL): Change From Baseline in Pediatric Quality of Life Inventory (Peds-QL) Score
timeFrame: Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
measure: HRQoL: Change From Baseline in EuroQol Five Dimensions Questionnaire (EQ-5D) Score
timeFrame: Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
measure: Treatment Preference and Satisfaction: Change From Baseline in Assessment of Life Quality Index (LQI) Score
timeFrame: Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
measure: Treatment Preference and Satisfaction: Change From Baseline in Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) Score
timeFrame: Epoch 1: Baseline (First Infusion); Study Epoch 2: Up to Month 36
measure: Treatment Preference and Satisfaction: Number of Participants Who Completed Treatment Preference Questionnaire
timeFrame: Study Epoch 2: Up to Month 36
measure: Health Resource Utilization: Days Not Able to go to School or Work, or to Perform Normal Daily Activities
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Health Resource Utilization: Days on Antibiotics
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Health Resource Utilization: Number of Hospitalizations
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
measure: Health Resource Utilization: Number of Days Hospitalized Per Participant-Year
timeFrame: From first dose of study drug up to EOS (up to 4 years 9 months)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Medical Center
state: Alabama
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Miami
country: United States
facility: University of Miami Pediatric Allergy and Immunology
state: Florida
city: Saint Petersburg
country: United States
facility: University of South Florida Physician Group
state: Florida
city: Albany
country: United States
facility: Georgia Pollens Clinical Research Centers, Inc.
state: Georgia
city: Atlanta
country: United States
facility: Emory Healthcare
state: Georgia
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Buffalo
country: United States
facility: Women & Children's Hospital of Buffalo
state: New York
city: Great Neck
country: United States
facility: Northwell Health, Inc. PRIME
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Children's Hospital
state: New York
city: Charlotte
country: United States
facility: Carolinas Healthcare System
state: North Carolina
city: Charlotte
country: United States
facility: Allergy Asthma & Immunology Relief of Charlotte
state: North Carolina
city: Oklahoma City
country: United States
facility: OK Institute of Allergy & Asthma Clinical Research, LLC
state: Oklahoma
city: Tulsa
country: United States
facility: Vital Prospects Clinical Research Institute, P.C.
state: Oklahoma
city: Dallas
country: United States
facility: Allergy Partners of North Texas Research
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Fairfax
country: United States
facility: Section on Immunopathogenesis and Clinical Immunology
state: Virginia
city: Charleston
country: United States
facility: Marshall University Joan C. Edwards School of Medicine
state: West Virginia
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: