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

• Register: ClinicalTrials.gov
• Last refreshed on: 1 March 2021
• Main ID: NCT03116347
• Date of registration: 12/04/2017
• Prospective Registration: Yes
• Primary sponsor: Baxalta now part of Shire
• Public title: Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric PIDD Subjects
• Scientific title: Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric Subjects With Primary Immunodeficiency Diseases
• Date of first enrolment: June 13, 2017
• Target sample size: 42
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03116347
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Czechia, Denmark, France, Greece, Slovakia, Sweden, United Kingdom

Contacts

• Name: Study Director
• Affiliation: Shire

Key inclusion & exclusion 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.



Age minimum: 2 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Immunodeficiency Diseases (PID)

Intervention(s)

Biological: Cuvitru

Biological: KIOVIG

Biological: HYQVIA

Primary Outcome(s)

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

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

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

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

Secondary Outcome(s)

Rate of local adverse reactions [Time Frame: Throughout the study period of approximately five years]

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

Number of all adverse events [Time Frame: Throughout the study period of approximately five years]

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 systemic adverse events [Time Frame: Throughout the study period of approximately five years]

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 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)]

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)]

Health-related Quality of Life (HRQoL): PedsQL™ [Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years)]

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

Rate of all adverse events [Time Frame: Throughout the study period of approximately five years]

Rate of all serious adverse events [Time Frame: Throughout the study period of approximately five years]

Rate of all adverse reactions [Time Frame: Throughout the study period of approximately five years]

Trough levels of Immunoglobulin G (IgG) [Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years)]

Rate of systemic adverse events [Time Frame: Throughout the study period of approximately five years]

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

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)]

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

Number of local adverse events [Time Frame: Throughout the study period of approximately five years]

Number of systemic adverse reactions [Time Frame: Throughout the study period of approximately five years]

Percentage of participants who maintain a treatment interval of three or four weeks in Epoch 2 for 12 months [Time Frame: 12 months]

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

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 all serious adverse events [Time Frame: Throughout the study period of approximately five years]

Number of local adverse reactions [Time Frame: Throughout the study period of approximately five years]

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)]

Rate of local adverse events [Time Frame: Throughout the study period of approximately five years]

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)]

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 of systemic adverse reactions [Time Frame: Throughout the study period of approximately five years]

EuroQoL (Quality of Life)-5 Dimensions (EQ-5D) [Time Frame: Epoch 1 (up to 6 weeks) and Epoch 2 (up to 3 years)]

Number of all adverse reactions [Time Frame: Throughout the study period of approximately five years]

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]

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

Secondary ID(s)

2016-003438-26

161504

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Baxalta Innovations GmbH, now part of Shire