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

• Register: ClinicalTrials.gov
• Last refreshed on: 10 October 2022
• Main ID: NCT03277313
• Date of registration: 07/09/2017
• Prospective Registration: Yes
• Primary sponsor: Baxalta now part of Shire
• Public title: Efficacy, Safety, Tolerability, Immunogenicity and Pharmacokinetic Evaluation of HYQVIA in Pediatric PIDD Subjects
• Scientific title: Efficacy, Safety, Tolerability, Immunogenicity and Pharmacokinetic Evaluation of HYQVIA in Pediatric Subjects With Primary Immunodeficiency Diseases
• Date of first enrolment: September 25, 2017
• Target sample size: 44
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03277313
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Prevention. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Study Director
• Affiliation: Shire

Key inclusion & exclusion 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.



Age minimum: 2 Years
Age maximum: 15 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Immunodeficiency Diseases (PID)

Intervention(s)

Biological: HYQVIA

Biological: GAMMAGARD LIQUID

Primary Outcome(s)

Rate of acute serious bacterial infections [Time Frame: Throughout the study period of approximately six years]

Secondary Outcome(s)

Health Resource Utilization: Number of hospitalizations [Time Frame: Throughout the study period of approximately six years]

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]

Infusions that are discontinued, slowed, or interrupted due to an adverse event (AE) [Time Frame: Epoch 2 (up to 3 years)]

Number of systemic adverse events (AEs), related and not related [Time Frame: Throughout the study period of approximately six years]

Treatment Preference and Satisfaction: Assessment of Treatment Preference Questionnaire [Time Frame: Epoch 2: months 12, 24, and 36]

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 six years]

Number of all adverse events (AEs), related and not related [Time Frame: Throughout the study period of approximately six years]

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

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

Number of all infections [Time Frame: Throughout the study period of approximately six 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)]

Number of all causally related and/or temporally associated adverse events (AEs) per infusion (excluding infections) [Time Frame: Throughout the study period of approximately six years]

Pharmacokinetics (PK) assessment: minimum concentration (Cmin) [Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion (Day 2- only for participants =12 years of age), Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval)]

Number of serious adverse events (SAEs), related and not related [Time Frame: Throughout the study period of approximately six years]

Health Resource Utilization: Number of acute physician visits [Time Frame: Throughout the study period of approximately six years]

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)]

Number of infusion sites (needle sticks) per infusion/month [Time Frame: Epoch 2 (up to 3 years)]

Number of local adverse events (AEs), related and not related [Time Frame: Throughout the study period of approximately six 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)]

Pharmacokinetics (PK) assessment: Area under the curve (AUC) [Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion (Day 2- only for participants =12 years of age), Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval)]

Health Resource Utilization: Number of days hospitalized [Time Frame: Throughout the study period of approximately six years]

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]

Rate of all causally related and/or temporally associated adverse events (AEs) per infusion (excluding infections) [Time Frame: Throughout the study period of approximately six years]

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

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.]

Pharmacokinetics (PK) assessment: maximum concentration (Cmax) [Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion (Day 2- only for participants =12 years of age), Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval)]

Rate of all adverse events (AEs), related and not related [Time Frame: Throughout the study period of approximately six years]

Rate of local adverse events (AEs), related and not related [Time Frame: Throughout the study period of approximately six years]

Number of infusions per month [Time Frame: Epoch 2 (up to 3 years)]

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

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]

Pharmacokinetics (PK) assessment: Clearance (CL) [Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion (Day 2- only for participants =12 years of age), Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval)]

Rate of systemic adverse events (AEs), related and not related [Time Frame: Throughout the study period of approximately six years]

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]

Rates of all AEs (excluding infections) [Time Frame: Throughout the study period of approximately six years]

Trough levels of specific antibodies to clinically relevant pathogens [Time Frame: Epoch 2, Study Epoch 2, Year 2: Months 24, and 36]

Health Resource Utilization: Days on antibiotics [Time Frame: Throughout the study period of approximately six 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 weeks to reach final dose interval [Time Frame: Epoch 1 (up to 6 weeks)]

Pharmacokinetics (PK) assessment: terminal half-life (T 1/2) [Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion (Day 2- only for participants =12 years of age), Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval)]

Pharmacokinetics (PK) assessment: time to maximum concentration (Tmax) [Time Frame: Pre-infusion, within one hour of infusion start time. Post-infusion (Day 2- only for participants =12 years of age), Days 4, 10, and either day 21 (for 3 week treatment interval), or day 28 (for 4 week treatment interval)]

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.]

Rate of serious adverse events (SAEs), related and not related [Time Frame: Throughout the study period of approximately six years]

Treatment Preference and Satisfaction: Assessment of Life Quality Index (LQI) [Time Frame: Epoch 1: Baseline (First Infusion); Epoch 2: months 12, 24, and 36]

Secondary ID(s)

161503

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Baxalta Innovations GmbH, now part of Shire