search
Back to results

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

Primary Purpose

Primary Immunodeficiency

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
IgPro20
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Immunodeficiency

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Clinical Research Center of Alabama
  • Research Solutions of Arizona
  • University of Southern Florida
  • Georgia Pollens Clinical Research Centers
  • Long Island Jewish Medical Center
  • Icahn Medical Institute
  • Center for Clinical Research Rochester General Hospital
  • Levine Children's Hospital
  • Duke University School of Medicine
  • Medical College of Wisconsin
  • The Ottawa Hospital
  • McGill University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

IgPro20 (Pump-Assisted Volume Cohort)

IgPro20 (Pump Assisted Flow Rate Cohort)

IgPro20 (Manual Push Flow Rate Cohort)

Arm Description

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

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Rate of Treatment-emergent Adverse Events (TEAEs) Per Infusion
Adverse event rate per infusion = number of adverse events/total number of infusions prior to subject's start date of non-response. Only events are included which start prior to subject's start date of non-response.
Rate of Local TEAEs Per Infusion
Local adverse event rate per infusion = number of local adverse events/total number of infusions prior to subject's start date of non-response. Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC (Not Elsewhere Classified)", "infusion site reactions", and "injection site reactions". Only events are included which start prior to subject's start date of non-response.
Time to Onset of Local TEAEs
Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions". Only events are included which start prior to subject's start date of non-response.
Intensity of Local TEAEs
Mild = A type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate = A type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the subject. Severe = A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Only events are included which start prior to subject's start date of non-response.
Duration of Local TEAEs
Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions".
Tolerability of Infusions
Tolerability = number of infusions without severe local adverse events / total number of infusions. Severe = A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Only events are included which start prior to subject's start date of non-response.

Full Information

First Posted
January 23, 2017
Last Updated
March 16, 2020
Sponsor
CSL Behring
search

1. Study Identification

Unique Protocol Identification Number
NCT03033745
Brief Title
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

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Completed
Study Start Date
February 1, 2017 (Actual)
Primary Completion Date
December 14, 2018 (Actual)
Study Completion Date
December 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Immunodeficiency

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IgPro20 (Pump-Assisted Volume Cohort)
Arm Type
Experimental
Arm Description
Weekly volumes per injection site of 25 mL up to 50 mL administered subcutaneously.
Arm Title
IgPro20 (Pump Assisted Flow Rate Cohort)
Arm Type
Experimental
Arm Description
Weekly flow rates per injection site of 25 mL/hour up to 100 mL/hour administered subcutaneously.
Arm Title
IgPro20 (Manual Push Flow Rate Cohort)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
IgPro20
Other Intervention Name(s)
Hizentra
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Responders
Description
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.
Time Frame
At the end of 4 weeks for each planned infusion parameter
Secondary Outcome Measure Information:
Title
Rate of Treatment-emergent Adverse Events (TEAEs) Per Infusion
Description
Adverse event rate per infusion = number of adverse events/total number of infusions prior to subject's start date of non-response. Only events are included which start prior to subject's start date of non-response.
Time Frame
At the end of 4 weeks for each planned infusion parameter
Title
Rate of Local TEAEs Per Infusion
Description
Local adverse event rate per infusion = number of local adverse events/total number of infusions prior to subject's start date of non-response. Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC (Not Elsewhere Classified)", "infusion site reactions", and "injection site reactions". Only events are included which start prior to subject's start date of non-response.
Time Frame
At the end of 4 weeks for each planned infusion parameter
Title
Time to Onset of Local TEAEs
Description
Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions". Only events are included which start prior to subject's start date of non-response.
Time Frame
At the end of 4 weeks for each planned infusion parameter
Title
Intensity of Local TEAEs
Description
Mild = A type of AE that is usually transient and may require only minimal treatment or therapeutic intervention. The event does not generally interfere with usual activities of daily living. Moderate = A type of AE that is usually alleviated with additional specific therapeutic intervention. The event interferes with usual activities of daily living, causing discomfort but poses no significant or permanent risk of harm to the subject. Severe = A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Only events are included which start prior to subject's start date of non-response.
Time Frame
At the end of 4 weeks for each planned infusion parameter
Title
Duration of Local TEAEs
Description
Local Adverse Events: comprises all events reported within the MedDRA high level terms "administration site reactions NEC", "infusion site reactions", and "injection site reactions".
Time Frame
At the end of 4 weeks for each planned infusion parameter
Title
Tolerability of Infusions
Description
Tolerability = number of infusions without severe local adverse events / total number of infusions. Severe = A type of AE that interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention. Only events are included which start prior to subject's start date of non-response.
Time Frame
At the end of 4 weeks for each planned infusion parameter

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Physician
Organizational Affiliation
CSL Behring
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Research Center of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Facility Name
Research Solutions of Arizona
City
Litchfield Park
State/Province
Arizona
ZIP/Postal Code
85340
Country
United States
Facility Name
University of Southern Florida
City
Saint Petersburg
State/Province
Florida
ZIP/Postal Code
33701
Country
United States
Facility Name
Georgia Pollens Clinical Research Centers
City
Albany
State/Province
Georgia
ZIP/Postal Code
31707
Country
United States
Facility Name
Long Island Jewish Medical Center
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Facility Name
Icahn Medical Institute
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Center for Clinical Research Rochester General Hospital
City
Rochester
State/Province
New York
ZIP/Postal Code
14607
Country
United States
Facility Name
Levine Children's Hospital
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28203
Country
United States
Facility Name
Duke University School of Medicine
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
McGill University
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H4A3J1
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33409867
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.
Results Reference
derived
PubMed Identifier
33025378
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs