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Efficacy, Safety, Tolerability, Immunogenicity and Pharmacokinetic Evaluation of HYQVIA in Pediatric PIDD Subjects

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ClinicalTrials.gov Identifier: NCT03277313
Recruitment Status : Recruiting
First Posted : September 11, 2017
Last Update Posted : December 7, 2018
Sponsor:
Collaborator:
Baxalta Innovations GmbH, now part of Shire
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

September 7, 2017
September 11, 2017
December 7, 2018
October 17, 2017
May 30, 2023   (Final data collection date for primary outcome measure)
Rate of acute serious bacterial infections [ Time Frame: Throughout the study period of approximately five years ]
The rate of acute serious bacterial infections defined as the mean number of acute serious bacterial infections per participant per year.
Same as current
Complete list of historical versions of study NCT03277313 on ClinicalTrials.gov Archive Site
  • Number of all infections [ Time Frame: Throughout the study period of approximately five years ]
    Number of all infections per patient-year
  • Trough levels of immunoglobulin G (IgG) and IgG subclasses [ Time Frame: Epoch 2, Year 1: Months 0, 6, and 12. Study Epoch 2, Year 2: Months 18, 24, 30, and 36 ]
    Trough levels of immunoglobulin G (IgG) and IgG subclasses for Study Epoch 2
  • Trough levels of specific antibodies to clinically relevant pathogens [ Time Frame: Epoch 2, Year 1: Month 6. Study Epoch 2, Year 2: Months 24, and 36 ]
    Clinically relevant pathogens include: Clostridium tetani toxoid, Haemophilus influenzae, and Hepatitis B virus [HBV]) for Study Epoch 2
  • Pharmacokinetics (PK) assessment: Area under the curve (AUC) [ Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval) ]
    To facilitate comparisons across different dosing intervals (three and four weeks), immunoglobulin G (IgG) exposure (AUC) will be normalized by week.
  • Pharmacokinetics (PK) assessment: Clearance (CL) [ Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval) ]
    PK analyses will use the actual observed sample drawing times, not the nominal times specified in the protocol.
  • Pharmacokinetics (PK) assessment: maximum concentration (Cmax) [ Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval) ]
    PK analyses will use the actual observed sample drawing times, not the nominal times specified in the protocol.
  • Pharmacokinetics (PK) assessment: minimum concentration (Cmin) [ Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval) ]
    PK analyses will use the actual observed sample drawing times, not the nominal times specified in the protocol.
  • Pharmacokinetics (PK) assessment: time to maximum concentration (Tmax) [ Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval) ]
    PK analyses will use the actual observed sample drawing times, not the nominal times specified in the protocol.
  • Pharmacokinetics (PK) assessment: terminal half-life (T 1/2) [ Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval) ]
    PK analyses will use the actual observed sample drawing times, not the nominal times specified in the protocol.
  • Number of serious adverse events (SAEs), related and not related [ Time Frame: Throughout the study period of approximately five years ]
    Number of serious adverse events (SAEs) per infusion (excluding infections), related and not related
  • Rate of serious adverse events (SAEs), related and not related [ Time Frame: Throughout the study period of approximately five years ]
    Rate of serious adverse events (SAEs) per infusion (excluding infections), related and not related
  • Number of all adverse events (AEs), related and not related [ Time Frame: Throughout the study period of approximately five years ]
    Number of all adverse events (AEs) per infusion (excluding infections), related and not related
  • Rate of all adverse events (AEs), related and not related [ Time Frame: Throughout the study period of approximately five years ]
    Rate of all adverse events (AEs) per infusion (excluding infections), related and not related
  • Number of local adverse events (AEs), related and not related [ Time Frame: Throughout the study period of approximately five years ]
    Number of local adverse events (AEs) per infusion (excluding infections), related and not related
  • Rate of local adverse events (AEs), related and not related [ Time Frame: Throughout the study period of approximately five years ]
    Rate of local adverse events (AEs) per infusion (excluding infections), related and not related
  • Number of systemic adverse events (AEs), related and not related [ Time Frame: Throughout the study period of approximately five years ]
    Number of systemic adverse events (AEs) per infusion (excluding infections), related and not related
  • Rate of systemic adverse events (AEs), related and not related [ Time Frame: Throughout the study period of approximately five years ]
    Rate of systemic adverse events (AEs) per infusion (excluding infections), related and not related
  • Number of all temporally associated adverse events (AEs) per infusion (excluding infections) [ Time Frame: From beginning of infusion to 72 hours of completion of infusion. ]
    Temporally associated AEs are all AEs which begin during the infusion or within 72 hours of completion of infusion.
  • Rate of all temporally associated adverse events (AEs) per infusion (excluding infections) [ Time Frame: From beginning of infusion to 72 hours of completion of infusion. ]
    Temporally associated AEs are all AEs which begin during the infusion or within 72 hours of completion of infusion.
  • Number of all causally related and/or temporally associated adverse events (AEs) per infusion (excluding infections) [ Time Frame: Throughout the study period of approximately five years ]
    Number per infusion (excluding infections) of all causally related and/or temporally associated AEs
  • Rate of all causally related and/or temporally associated adverse events (AEs) per infusion (excluding infections) [ Time Frame: Throughout the study period of approximately five years ]
    Rate per infusion (excluding infections) of all causally related and/or temporally associated AEs
  • Rates of all AEs (excluding infections) [ Time Frame: Throughout the study period of approximately five years ]
    Rates of all AEs (excluding infections) defined as number of AEs categorized by MedDRA preferred terms, seriousness, and severity, divided by the number of infusions
  • Number of participants who develop positive titer of binding or neutralizing antibodies to rHuPH20 [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    Number of participants who develop positive titer (≥ 160) of binding or neutralizing antibodies to rHuPH20
  • Percentage of participants who develop positive titer of binding or neutralizing antibodies to rHuPH20 [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    Percentage of participants who develop positive titer (≥ 160) of binding or neutralizing antibodies to rHuPH20
  • Number of infusions per month [ Time Frame: Epoch 2 (up to 3 years) ]
    Median number of infusions per month per participant
  • Number of infusion sites (needle sticks) per infusion/month [ Time Frame: Epoch 2 (up to 3 years) ]
    Median number of infusion sites (needle sticks) per infusion/month
  • Duration of infusion [ Time Frame: Epoch 2 (up to 3 years) ]
    Median duration of infusion
  • Maximum infusion rate / site [ Time Frame: Epoch 2 (up to 3 years) ]
    Median maximum infusion rate / site
  • Infusion volume / site [ Time Frame: Epoch 2 (up to 3 years) ]
    Median infusion volume / site
  • Infusions that are discontinued, slowed, or interrupted due to an adverse event (AE) [ Time Frame: Epoch 2 (up to 3 years) ]
    Number of infusions that are discontinued, slowed, or interrupted due to an adverse event (AE)
  • Percentage of infusions that are discontinued, slowed, or interrupted due to an adverse event (AE) [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    Percentage of infusions that are discontinued, slowed, or interrupted due to an AE
  • Number of weeks to reach final dose interval [ Time Frame: Epoch 1 (up to 6 weeks) ]
    Median number of weeks to reach final dose interval (three weeks or four weeks) (Epoch 1)
  • Percentage of participants who achieve a treatment interval of three or four weeks in Epoch 2 [ Time Frame: 3 or 4 weeks (dependent on treatment interval) ]
    Epoch 2: HyQvia treatment at the following intervals: - For intravenous (IV)- pre-treated participants: every three or four weeks, depending on the participant's previous IV dosing schedule. - For subcutaneous (SC) - pre-treated participants: every three or four weeks, a t the discretion of investigator and participant. - For HyQvia pre-treated participants: No change in frequency of administration
  • Percentage of participants who maintain a treatment interval of three or four weeks in Epoch 2 for 12 months [ Time Frame: 12 months ]
    Epoch 2: HyQvia treatment at the following intervals: - For intravenous (IV)- pre-treated participants: every three or four weeks, depending on the participant's previous IV dosing schedule. - For subcutaneous (SC) - pre-treated participants: every three or four weeks, a t the discretion of investigator and participant. - For HyQvia pre-treated participants: No change in frequency of administration
  • Health-related Quality of Life (HRQoL): Pediatric Quality of Life Inventory (Peds-QL) [ Time Frame: Epoch 1: Baseline (First Infusion); Epoch 2: months 12, 24, and 36 ]
    The Peds-QL is a generic Health-Related Quality of Life (HRQoL) instrument designed specifically for a pediatric population.
  • Health-related Quality of Life (HRQoL): EuroQol five dimensions questionnaire (EQ-5D) [ Time Frame: Epoch 1: Baseline (First Infusion); Epoch 2: months 12, 24, and 36 ]
    EQ-5D is a participant answered questionnaire scoring 5 dimensions - mobility, self-case, usual activities, pain/discomfort and anxiety/depression.
  • Treatment Preference and Satisfaction: Assessment of Life Quality Index (LQI) [ Time Frame: Epoch 1: Baseline (First Infusion); Epoch 2: months 12, 24, and 36 ]
    The LQI is validated questionnaire assessing patient perceptions of their HRQoL and their treatment specifically among patients who use immunoglobulin therapy. This questionnaire covers 4 domains: Treatment Interferences, Therapy-related Problems, Therapy Setting, and Treatment Costs.
  • Treatment Preference and Satisfaction: Assessment of Treatment Satisfaction and Medication Questionnaire (TSQM-9) [ Time Frame: Epoch 1: Baseline (First Infusion); Epoch 2: months 12, 24, and 36 ]
    Treatment Satisfaction Questionnaire for Medication (TSQM-9) is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications.
  • Treatment Preference and Satisfaction: Assessment of Treatment Preference Questionnaire [ Time Frame: Epoch 2: months 12, 24, and 36 ]
    The treatment preference questionnaire, internally developed by the study sponsor, is a self-administered, non-validated scale assessing patient preference for various attributes of immunoglobulin G (IgG) therapy.
  • Health Resource Utilization: Days not able to go to school or work, or to perform normal daily activities [ Time Frame: Throughout the study period of approximately five years ]
    Days not able to go to school or work, or to perform normal daily activities due to infection or other illnesses per patient-year
  • Health Resource Utilization: Days on antibiotics [ Time Frame: Throughout the study period of approximately five years ]
    Days on antibiotics per patient-year
  • Health Resource Utilization: Number of hospitalizations [ Time Frame: Throughout the study period of approximately five years ]
    Number of hospitalizations, indication for the hospitalization (infection or non-infection)
  • Health Resource Utilization: Number of days hospitalized [ Time Frame: Throughout the study period of approximately five years ]
    Number of days hospitalized per patient-year
  • Health Resource Utilization: Number of acute physician visits [ Time Frame: Throughout the study period of approximately five years ]
    Number of acute physician visits (office and emergency room) due to infection or other illnesses per patient-year
Same as current
Not Provided
Not Provided
 
Efficacy, Safety, Tolerability, Immunogenicity and Pharmacokinetic Evaluation of HYQVIA in Pediatric PIDD Subjects
Efficacy, Safety, Tolerability, Immunogenicity and Pharmacokinetic Evaluation of HYQVIA in Pediatric Subjects With Primary Immunodeficiency Diseases
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).
Not Provided
Interventional
Phase 3
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Primary Immunodeficiency Diseases (PID)
  • Biological: HYQVIA
    Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (IGI, 10% with rHuPH20)
    Other Name: IGI 10% with rHuPH20
  • Biological: GAMMAGARD LIQUID
    GAMMAGARD LIQUID IGI (Human), 10% Solution
    Other Names:
    • IGI
    • 10%
  • Experimental: Epoch 1
    Pediatric patients with primary immunodeficiency disease (PIDD) who are on intravenous (IV) or non-HYQVIA subcutaneous (SC) treatment with immunoglobulin (IV-pre-treated, SC-pre-treated) will be enrolled and treated with HYQVIA subcutaneously with a dose or interval ramp-up period of up to six weeks.
    Intervention: Biological: HYQVIA
  • Experimental: Epoch 2

    HYQVIA treatment at the following intervals:

    • For intravenous (IV)-pre-treated participants: every three or four weeks, depending on the participant's previous IV dosing schedule.
    • For subcutaneous (SC)-pre-treated participants: every three or four weeks, at the discretion of investigator and participant.

    After one year in Epoch 2, the anti-rHuPH20 binding antibody assay results during that year will be used to decide the next steps in the study:

    • Participants with anti-rHuPH20 antibody titer < 160 at all time-points during the study will complete the study completion visit at the next possible occasion following the 12-months visit.
    • Participants with anti-rHuPH20 antibody titer ≥ 160 during the study and/or at the last measurement will continue in Epoch 2 for an additional two years of HYQVIA treatment and observation, and complete the study completion visits at the next possible occasion following the 36-months visit.
    Intervention: Biological: HYQVIA
  • Active Comparator: Epoch 3
    Safety follow-up for participants whose anti-rHuPH20 antibody titer was ≥ 160 during Epoch 1 or Epoch 2 and who experience either related serious adverse event (SAE) or a related severe adverse event (AE)
    Intervention: Biological: GAMMAGARD LIQUID
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
Same as current
May 30, 2023
May 30, 2023   (Final data collection date for primary outcome measure)

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 1 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.
Sexes Eligible for Study: All
2 Years to 15 Years   (Child)
No
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com
United States
 
 
NCT03277313
161503
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Shire ( Baxalta now part of Shire )
Baxalta now part of Shire
Baxalta Innovations GmbH, now part of Shire
Study Director: Study Director Shire
Shire
December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP