Safety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)

NCT ID: NCT03033745

Last Updated: 2020-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-01
• Study Completion Date: 2018-12-14

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.

Conditions

Primary Immunodeficiency

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IgPro20 (Pump-Assisted Volume Cohort)

Weekly volumes per injection site of 25 mL up to 50 mL administered subcutaneously.

Group Type: EXPERIMENTAL

IgPro20

Intervention Type: DRUG

A liquid formulation of normal human IgG at a concentration of 20% administered as a subcutaneous infusion at a dose prescribed by subject's physician prior to study entry.

IgPro20 (Pump Assisted Flow Rate Cohort)

Weekly flow rates per injection site of 25 mL/hour up to 100 mL/hour administered subcutaneously.

Group Type: EXPERIMENTAL

IgPro20

Intervention Type: DRUG

A liquid formulation of normal human IgG at a concentration of 20% administered as a subcutaneous infusion at a dose prescribed by subject's physician prior to study entry.

IgPro20 (Manual Push Flow Rate Cohort)

Frequent (ie, 2 to 7 times per week) flow rates 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) administered subcutaneously.

Group Type: EXPERIMENTAL

IgPro20

Intervention Type: DRUG

A liquid formulation of normal human IgG at a concentration of 20% administered as a subcutaneous infusion at a dose prescribed by subject's physician prior to study entry.

Interventions

IgPro20

A liquid formulation of normal human IgG at a concentration of 20% administered as a subcutaneous infusion at a dose prescribed by subject's physician prior to study entry.

Intervention Type: DRUG

Other Intervention Names

Hizentra

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.

• Minimum Eligible Age: 2 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSL Behring

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Physician

Role: STUDY_DIRECTOR

CSL Behring

Locations

Clinical Research Center of Alabama

Birmingham, Alabama, United States

Research Solutions of Arizona

Litchfield Park, Arizona, United States

University of Southern Florida

St. Petersburg, Florida, United States

Georgia Pollens Clinical Research Centers

Albany, Georgia, United States

Long Island Jewish Medical Center

Great Neck, New York, United States

Icahn Medical Institute

New York, New York, United States

Center for Clinical Research Rochester General Hospital

Rochester, New York, United States

Levine Children's Hospital

Charlotte, North Carolina, United States

Duke University School of Medicine

Durham, North Carolina, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

The Ottawa Hospital

Ottawa, Ontario, Canada

McGill University

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 33409867 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33025378 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-003799-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IgPro20_4004

Identifier Type: -

Identifier Source: org_study_id