Primary ImmunodeficiencyPhase 4NCT03033745
Safety and Tolerability of Higher Infusion Parameters of IgPro20 (Hizentra) in Subjects With Primary Immunodeficiency (PID)
A Phase 4 study testing IgPro20 in people with Primary Immunodeficiency, run by CSL Behring at 12 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Primary Immunodeficiency
- What is being tested?
- IgPro20
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 12 sitesin 2 countries
- Study dates
- 1 Feb 2017to 14 Dec 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
12 sites in 2 countries.
12 sites in 2 countries
United States10 sites
Georgia Pollens Clinical Research Centers
Albany, Georgia, 31707
Clinical Research Center of Alabama
Birmingham, Alabama, 35209
Levine Children's Hospital
Charlotte, North Carolina, 28203
Duke University School of Medicine
Durham, North Carolina, 27705
Long Island Jewish Medical Center
Great Neck, New York, 11021
Research Solutions of Arizona
Litchfield Park, Arizona, 85340
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Icahn Medical Institute
New York, New York, 10029
Center for Clinical Research Rochester General Hospital
Rochester, New York, 14607
University of Southern Florida
St. Petersburg, Florida, 33701
Canada2 sites
McGill University
Montreal, Quebec, H4A3J1
The Ottawa Hospital
Ottawa, Ontario, K1H 8L6
About this study
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
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
- Being tested
- IgPro20
- Medical subject headings
- Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IgPro20Drug
Also called Hizentra
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.
| Study group | Role | What they receive |
|---|---|---|
| IgPro20 (Pump-Assisted Volume Cohort) | Experimental | Weekly volumes per injection site of 25 mL up to 50 mL administered subcutaneously. Receives: 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. Receives: 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. Receives: Drug: IgPro20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At the end of 4 weeks for each planned infusion parameter
Secondary outcomes (6)
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.
Measured: At the end of 4 weeks for each planned infusion parameter
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.
Measured: At the end of 4 weeks for each planned infusion parameter
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.
Measured: At the end of 4 weeks for each planned infusion parameter
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.
Measured: At the end of 4 weeks for each planned infusion parameter
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".
Measured: At the end of 4 weeks for each planned infusion parameter
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.
Measured: At the end of 4 weeks for each planned infusion parameter
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2017 (estimated)
- Study start1 Feb 2017
- Primary completion14 Dec 2018
- Study completion14 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Primary ImmunodeficiencyStudies of the same condition, open and under way.
- More trials run by CSL BehringThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Physician, Study director, CSL Behring
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03033745
- Sponsor's protocol ID
- IgPro20_4004
- Other IDs
- 2016-003799-33, 2016
- Status last verified
- Mar 2020
- First submitted
- 23 Jan 2017
- Last updated
- 25 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33409867Cowan 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.
PubMed 33025378
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03033745
- Acronym / sponsor ID
- IgPro20_4004
- Conditions
- Primary Immunodeficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 14 Dec 2018 (actual)
- Study completion
- 14 Dec 2018 (actual)
- First posted
- 27 Jan 2017 (estimated)
- Results
- Posted 13 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| IgPro20 (Pump-Assisted Volume Cohort) | Experimental | Drug: IgPro20Weekly volumes per injection site of 25 mL up to 50 mL administered subcutaneously. |
| IgPro20 (Pump Assisted Flow Rate Cohort) | Experimental | Drug: IgPro20Weekly flow rates per injection site of 25 mL/hour up to 100 mL/hour administered subcutaneously. |
| IgPro20 (Manual Push Flow Rate Cohort) | Experimental | Drug: IgPro20Frequent (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. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IgPro20Also: HizentraA 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. | Drug | IgPro20 (Manual Push Flow Rate Cohort), IgPro20 (Pump Assisted Flow Rate Cohort), IgPro20 (Pump-Assisted Volume Cohort) |
Primary outcome
Percentage of Responders
Time frame: At the end of 4 weeks for each planned infusion parameter
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.
6 secondary outcomes
Rate of Treatment-emergent Adverse Events (TEAEs) Per Infusion
Time frame: At the end of 4 weeks for each planned infusion parameter
Rate of Local TEAEs Per Infusion
Time frame: At the end of 4 weeks for each planned infusion parameter
Time to Onset of Local TEAEs
Time frame: At the end of 4 weeks for each planned infusion parameter
Intensity of Local TEAEs
Time frame: At the end of 4 weeks for each planned infusion parameter
Duration of Local TEAEs
Time frame: At the end of 4 weeks for each planned infusion parameter
Tolerability of Infusions
Time frame: At the end of 4 weeks for each planned infusion parameter
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33409867Anderson 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.
- Derived from this study: PubMed 33025378Cowan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Physician study director
CSL Behring
12 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing IgPro20 in people with Primary Immunodeficiency, run by CSL Behring at 12 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Responders (time frame: At the end of 4 weeks for each planned infusion parameter). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03033745, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2020.