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Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric PIDD Subjects

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ClinicalTrials.gov Identifier: NCT03116347
Recruitment Status : Recruiting
First Posted : April 17, 2017
Last Update Posted : June 25, 2018
Sponsor:
Collaborator:
Baxalta Innovations GmbH, now part of Shire
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

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)

Condition or disease Intervention/treatment Phase
Primary Immunodeficiency Diseases (PID) Biological: HYQVIA Biological: KIOVIG Biological: Cuvitru Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric Subjects With Primary Immunodeficiency Diseases
Actual Study Start Date : May 30, 2017
Estimated Primary Completion Date : November 30, 2022
Estimated Study Completion Date : November 30, 2022


Arm Intervention/treatment
Experimental: EPOCH 1
Ramp up period for participants who were not treated with HyQvia prior to this study
Biological: HYQVIA
Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (IGI, 10% with rHuPH20)
Other Name: IGI 10% with rHuPH20

Experimental: EPOCH 2
Participants who were treated with HyQvia prior to this study, and those who completed the ramp up period (Epoch 1). After one year in Epoch 2, participants with anti-rHuPH20 antibody titer <160 at all time-points during the study will complete the study termination/completion visit at the next possible occasion. Participants with anti-rHuPH20 antibody titer ≥160 during the study and/or at the last measurement will continue for an additional two years of HyQvia treatment and observation.
Biological: HYQVIA
Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase (IGI, 10% with rHuPH20)
Other Name: IGI 10% with rHuPH20

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 a related serious adverse event (SAE) or a related severe adverse event (AE)
Biological: KIOVIG
100 mg/ml solution for infusion
Other Names:
  • IGI
  • 10%

Biological: Cuvitru
200 mg/ml solution for subcutaneous injection
Other Names:
  • [Immune Globulin Subcutaneous (Human)]
  • Immune Globulin Subcutaneous (Human)
  • 20% Solution




Primary Outcome Measures :
  1. Number of all severe related adverse events (AEs) per infusion (excluding infections) [ Time Frame: Throughout the study period of approximately five years ]
    Related AEs are possibly related or probably related AEs

  2. Rate of all severe related adverse events (AEs) per infusion (excluding infections) [ Time Frame: Throughout the study period of approximately five years ]
    Related AEs are possibly related or probably related AEs

  3. Number of related serious adverse events (SAEs) per infusion (excluding infections) [ Time Frame: Throughout the study period of approximately five years ]
    Related SAEs are possibly related or probably related SAEs

  4. Rate of related serious adverse events (SAEs) per infusion (excluding infections) [ Time Frame: Throughout the study period of approximately five years ]
    Related SAEs are possibly related or probably related SAEs


Secondary Outcome Measures :
  1. Trough levels of Immunoglobulin G (IgG) [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    For Study Epoch 1 and 2

  2. 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)-pretreated participants: every three or four weeks, depending on the participant's previous IV dosing schedule. - For subcutaneous (SC)-pretreated participants: every three or four weeks, at the discretion of investigator and participant. - For HyQvia pre-treated participants: No change

  3. 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)-pretreated participants: every three or four weeks, depending on the participant's previous IV dosing schedule. - For subcutaneous (SC)-pretreated participants: every three or four weeks, at the discretion of investigator and participant. - For HyQvia pre-treated participants: No change

  4. Number of local adverse events [ Time Frame: Throughout the study period of approximately five years ]
    Number of local adverse events (AEs) per infusion (excluding infections)

  5. Number of local adverse reactions [ Time Frame: Throughout the study period of approximately five years ]
    Number of local adverse reactions (ARs) per infusion (excluding infections)

  6. Rate of local adverse events [ Time Frame: Throughout the study period of approximately five years ]
    Rate of local adverse events (AEs) per infusion (excluding infections)

  7. Rate of local adverse reactions [ Time Frame: Throughout the study period of approximately five years ]
    Rate of local adverse reactions (ARs) per infusion (excluding infections)

  8. Number of systemic adverse events [ Time Frame: Throughout the study period of approximately five years ]
    Number of systemic adverse events (AEs) per infusion (excluding infections)

  9. Number of systemic adverse reactions [ Time Frame: Throughout the study period of approximately five years ]
    Number of systemic adverse reactions (ARs) per infusion (excluding infections)

  10. Rate of systemic adverse events [ Time Frame: Throughout the study period of approximately five years ]
    Rate of systemic adverse events (AEs) per infusion (excluding infections)

  11. Rate of systemic adverse reactions [ Time Frame: Throughout the study period of approximately five years ]
    Rate of systemic adverse reactions (ARs) per infusion (excluding infections)

  12. Number of all adverse events [ Time Frame: Throughout the study period of approximately five years ]
    Number of all adverse events (AEs) per infusion (excluding infections)

  13. Number of all adverse reactions [ Time Frame: Throughout the study period of approximately five years ]
    Number of all adverse reactions (ARs) per infusion (excluding infections)

  14. Rate of all adverse events [ Time Frame: Throughout the study period of approximately five years ]
    Rate of all adverse events (AEs) per infusion (excluding infections)

  15. Rate of all adverse reactions [ Time Frame: Throughout the study period of approximately five years ]
    Rate of all adverse reactions (ARs) per infusion (excluding infections)

  16. Number of all temporally associated adverse events (AEs) per infusion (excluding infections) [ Time Frame: Throughout the study period of approximately five years ]
    Temporally associated AEs are all AEs which occur during the infusion or within 72 hours of completion of infusion.

  17. Rate of all temporally associated adverse events (AEs) per infusion (excluding infections) [ Time Frame: Throughout the study period of approximately five years ]
    Temporally associated AEs are all AEs which occur during the infusion or within 72 hours of completion of infusion.

  18. 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 ]
    Temporally associated AEs are all AEs which occur during the infusion or within 72 hours of completion of infusion.

  19. 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 ]
    Temporally associated AEs are all AEs which occur during the infusion or within 72 hours of completion of infusion.

  20. Number of all serious adverse events [ Time Frame: Throughout the study period of approximately five years ]
    Number of all serious adverse events (SAEs) per infusion (excluding infections)

  21. Rate of all serious adverse events [ Time Frame: Throughout the study period of approximately five years ]
    Rate of all serious adverse events (SAEs) per infusion (excluding infections)

  22. 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

  23. 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

  24. Number of infusions per month per participant [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    Mean number of infusions per month per participant

  25. Number of infusion sites (needle sticks) per infusion/month per participant [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    Mean number of infusion sites (needle sticks) per infusion/month per participant

  26. Duration of infusion [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    Mean duration of infusion

  27. Maximum infusion rate/site [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    Mean maximum infusion rate/site

  28. Infusion volume/site [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    Mean infusion volume

  29. 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) ]
    Number of infusions that are discontinued, slowed, or interrupted due to an adverse event

  30. Percentage of infusions that are discontinued, slowed, or interrupted due to an adverse event [ 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 adverse event (AE)

  31. Number of weeks to reach final dose interval (3 weeks or 4 weeks) [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    Mean number of weeks to reach final dose interval (3 weeks or 4 weeks)

  32. Health Related Quality of Life: Treatment Satisfaction Questionnaire for Medication-9 (TSQM-9) [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    Treatment Satisfaction Questionnaire for Medication (TSQM) is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications.

  33. Health-related Quality of Life (HRQoL): PedsQL™ [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    The Peds-QL is a generic Health-Related Quality of Life (HR QoL) instrument designed specifically for a pediatric population.

  34. EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) [ Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years) ]
    EQ-5D is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03116347


Contacts
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Contact: Salvador Dominguez +1 617-588-8347 Salvador.Dominguez@shire.com
Contact: Shire Contact +1 866-842-5335 ClinicalTransparency@shire.com

Locations
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Denmark
Rigshospitalet Recruiting
København, Denmark, 2100
France
Groupe Hospitalier Pellegrin - Hôpital des Enfants Recruiting
Bordeaux, Gironde, France, 33076
Sweden
Queen Silvia Children's Hospital Recruiting
Goteborg, Sweden, 416 85
Dept. of Pediatric Oncology/Hematology/Immunology-Skånes Universitetssjukhus Recruiting
Lund, Sweden, 221 85
United Kingdom
Bristol Royal Hospital for Children Recruiting
Bristol, Avon, United Kingdom, BS2 8BJ
Leeds Children's Hospital Recruiting
Leeds, West Yorkshire, United Kingdom, LS1 3EX
Sponsors and Collaborators
Baxalta now part of Shire
Baxalta Innovations GmbH, now part of Shire
Investigators
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Study Director: Study Director Shire

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Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT03116347     History of Changes
Other Study ID Numbers: 161504
First Posted: April 17, 2017    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes
Immune System Diseases
Pharmaceutical Solutions
Immunoglobulins
Antibodies
gamma-Globulins
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs