Clinical trial NCT03033745: Safety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)
Official title: An Open-label Multicenter Study to Evaluate the Safety and Tolerability of Higher Infusion Parameters of Immune Globulin Subcutaneous (Human), 20% Liquid (Hizentra®) in Subjects With Primary Immunodeficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Primary Immunodeficiency
Lead sponsor: CSL Behring
Sponsor class: INDUSTRY
First posted: 2017-01-27
Enrollment: 49
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This multicenter, open-label, parallel-arm, non-randomized study is designed to evaluate safety and tolerability of higher infusion parameters of IgPro20 in subjects with primary immunodeficiency (PID). A total of 45 subjects (including at least 14 \[30%\] pediatric subjects ≤ 17 years of age and at least 9 \[20%\] obese subjects with body mass index \[BMI\] of ≥30 kg/m2) with confirmed PID will be evaluated in the study. The study will include three cohorts of 15 subjects each as follows: i) Pump-Assisted Volume Cohort (weekly infusions), volume per injection site of 25 mL up to 50 mL, ii) Pump Assisted Flow Rate Cohort (weekly infusions), flow rate per injection site of 25 mL/hour up to 100 mL/hour, iii) Manual Push Flow Rate Cohort (2 to 7 infusions per week), flow rate per injection site of 25 to 30 mL/hour up to 120 mL/hour (equivalent of approximately 0.5 mL/minute up to 2 mL/minute). Each cohort will test 3 infusion parameter levels (4 for the pump-assisted flow rate cohort), repeated at least 4 times over a duration of 12 weeks (16 weeks for the flow rate cohort). After 4 infusion weeks at each level, qualifying subjects (responders) will switch to the next infusion parameter level (eg, from 25 to 50 mL/h). During the study, the weekly dose will remain unchanged (as prescribed by treating physician, usually within 100-200 mg/kg per week range); only the respective infusion parameter under evaluation will change.


Eligibility criteria: Inclusion Criteria:

* Male or female on stable dose of IgPro20 (Hizentra) therapy.
* Women of childbearing potential must be using and agree to continue using medically approved contraception (which must be discussed with the study doctor) and must have a negative pregnancy test at screening.
* Subjects with PID, eg, with a diagnosis of common variable immunodeficiency or X-linked agammaglobulinemia, as defined by the Pan American Group for Immune Deficiency and the European Society of Immune Deficiencies.
* With infusion parameters as specified below:

Pump-Assisted Flow Rate Cohort subjects only

* Experience with pump-assisted infusions of IgPro20 at the tolerated flow rate of 25 mL/h per injection site for at least 1 month prior to Day 1.

Pump-Assisted Volume Cohort subjects only

* Total weekly IgPro20 dose of ≥ 50 mL (≥ 10 g).
* Experience with pump-assisted infusions of IgPro20 at tolerated volumes of 25 mL/injection site for at least 1 month prior to Day 1.

Manual Push Flow Rate Cohort subjects only

* Experience with frequent (2-7 times per week) infusions of IgPro20 at the tolerated flow rate of approximately 0.5 mL/min (equivalent of 25-30 mL/h) per injection site for at least 1 month prior to Day 1. The dose (volume) per injection site should not exceed 25 mL.

Exclusion Criteria:

* Ongoing serious bacterial infections at the time of screening.
* Other significant medical conditions that could increase the risk to the subject.
* Females who are pregnant, breast feeding, or planning a pregnancy during the course study.
* Participation in a study with an Investigational Medicinal Product (IMP) other than IgPro20 within three months prior to enrollment.

Primary outcomes:
measure: Percentage of Responders
timeFrame: At the end of 4 weeks for each planned infusion parameter
Secondary outcomes:
measure: Rate of Treatment-emergent Adverse Events (TEAEs) Per Infusion
timeFrame: At the end of 4 weeks for each planned infusion parameter
measure: Rate of Local TEAEs Per Infusion
timeFrame: At the end of 4 weeks for each planned infusion parameter
measure: Time to Onset of Local TEAEs
timeFrame: At the end of 4 weeks for each planned infusion parameter
measure: Intensity of Local TEAEs
timeFrame: At the end of 4 weeks for each planned infusion parameter
measure: Duration of Local TEAEs
timeFrame: At the end of 4 weeks for each planned infusion parameter
measure: Tolerability of Infusions
timeFrame: At the end of 4 weeks for each planned infusion parameter
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Clinical Research Center of Alabama
state: Alabama
city: Litchfield Park
country: United States
facility: Research Solutions of Arizona
state: Arizona
city: Saint Petersburg
country: United States
facility: University of Southern Florida
state: Florida
city: Albany
country: United States
facility: Georgia Pollens Clinical Research Centers
state: Georgia
city: Great Neck
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Icahn Medical Institute
state: New York
city: Rochester
country: United States
facility: Center for Clinical Research Rochester General Hospital
state: New York
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University School of Medicine
state: North Carolina
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montréal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: CSL Behring
name: Study Physician
role: STUDY_DIRECTOR
References:
citation: Anderson JT, Bonagura VR, Cowan J, Hsu C, Mustafa SS, Patel NC, Routes JM, Sriaroon P, Vinh DC, Hofmann JH, Praus M, Rojavin MA. Safety and Tolerability of Subcutaneous IgPro20 at High Infusion Parameters in Patients with Primary Immunodeficiency: Findings from the Pump-Assisted Administration Cohorts of the HILO Study. J Clin Immunol. 2021 Feb;41(2):458-469. doi: 10.1007/s10875-020-00912-5. Epub 2021 Jan 6.
citation: Cowan J, Bonagura VR, Lugar PL, Maglione PJ, Patel NC, Vinh DC, Hofmann JH, Praus M, Rojavin MA. Safety and Tolerability of Manual Push Administration of Subcutaneous IgPro20 at High Infusion Rates in Patients with Primary Immunodeficiency: Findings from the Manual Push Administration Cohort of the HILO Study. J Clin Immunol. 2021 Jan;41(1):66-75. doi: 10.1007/s10875-020-00876-6. Epub 2020 Oct 6.