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

NCT03033745 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: IgPro20_40042016-003799-33
• Study Type: interventional
• Target: 49
• Locations: 2 countries
• Sites: 12

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Responders

  A responder is a subject within the Pump-Assisted Cohorts that performs at least 3 out of 4 valid infusions at a certain infusion parameter level (weekly volumes per injection site of 25-50 mL; weekly flow rates per injection site of 25-100 mL/hour). Determination of a responder in the Manual Push Cohort is more complex due to the expected variable frequency of infusions per week (ie, 5-17) for different subjects. A responder within the Manual Push Cohort is a subject that performs a minimum number of valid infusions during 4 weeks corresponding to a certain flow rate level (\[ie, 2-7 times per week\], flow rates per injection site of 30-120 mL/hour). Valid infusions do not need to be consecutive, but each subject needs to adhere to the same schedule (number of infusions per week) throughout the study. An infusion parameter will be considered successful if at least one third (≥ 33%) of the subjects in the corresponding cohort are responders at that infusion parameter level.

  At the end of 4 weeks for each planned infusion parameter

Secondary Outcomes (6)

• Rate of Treatment-emergent Adverse Events (TEAEs) Per Infusion

  At the end of 4 weeks for each planned infusion parameter

• Rate of Local TEAEs Per Infusion

  At the end of 4 weeks for each planned infusion parameter

• Time to Onset of Local TEAEs

  At the end of 4 weeks for each planned infusion parameter

• Intensity of Local TEAEs

  At the end of 4 weeks for each planned infusion parameter

• Duration of Local TEAEs

  At the end of 4 weeks for each planned infusion parameter

Study Arms (3)

IgPro20 (Pump-Assisted Volume Cohort)

EXPERIMENTAL

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

Drug: IgPro20

IgPro20 (Pump Assisted Flow Rate Cohort)

EXPERIMENTAL

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

Drug: IgPro20

IgPro20 (Manual Push Flow Rate Cohort)

EXPERIMENTAL

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.

Drug: IgPro20

Interventions

IgPro20 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.

Also known as: Hizentra

IgPro20 (Manual Push Flow Rate Cohort); IgPro20 (Pump Assisted Flow Rate Cohort); IgPro20 (Pump-Assisted Volume Cohort)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• CSL Behring: lead

Study Sites (12)

Clinical Research Center of Alabama

Birmingham, Alabama, 35209, United States

Location

Research Solutions of Arizona

Litchfield Park, Arizona, 85340, United States

Location

University of Southern Florida

St. Petersburg, Florida, 33701, United States

Location

Georgia Pollens Clinical Research Centers

Albany, Georgia, 31707, United States

Location

Long Island Jewish Medical Center

Great Neck, New York, 11021, United States

Location

Icahn Medical Institute

New York, New York, 10029, United States

Location

Center for Clinical Research Rochester General Hospital

Rochester, New York, 14607, United States

Location

Levine Children's Hospital

Charlotte, North Carolina, 28203, United States

Location

Duke University School of Medicine

Durham, North Carolina, 27705, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

McGill University

Montreal, Quebec, H4A3J1, Canada

Location

Related Publications (2)

• 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.

  PMID: 33409867 DERIVED

• 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.

  PMID: 33025378 DERIVED

MeSH Terms

Conditions

Primary Immunodeficiency Diseases

Interventions

Hizentra

Condition Hierarchy (Ancestors)

Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Trial Registration Coordinator
• Organization: CSL Behring

clinicaltrials@cslbehring.com

610 878-4000

Study Officials

• Study Physician

  CSL Behring

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2017
• First Posted: January 27, 2017
• Study Start: February 1, 2017
• Primary Completion: December 14, 2018
• Study Completion: December 14, 2018
• Last Updated: March 25, 2020
• Results First Posted: January 13, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (10)