Primary Immune DeficiencyPhase 3NCT00419341
Study of Subcutaneous Immunoglobulin in Patients With PID Requiring IgG Replacement Therapy
A Phase 3 study testing Human Normal Immunoglobulin for Subcutaneous Administration in people with Primary Immune Deficiency, run by CSL Behring at 13 sites in United States.
Trial summary
The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID). Read more about this study
- Who is it for?
- Ages 2 to 75 years
- Conditions the study is for
- Primary Immune Deficiency
- What is being tested?
- Human Normal Immunoglobulin for Subcutaneous Administration
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 13 sitesUnited States
- Study dates
- Nov 2006to Oct 2008
- Phase
- Phase 3
- 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 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female aged 2 to 75 years
- Subjects with primary humoral immunodeficiency, namely with a diagnosis of: CVID (Common Variable Immunodeficiency) as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) or XLA (X-linked Agammaglobulinemia)
- Written informed consent
Who cannot join
- Newly diagnosed PID
- Evidence of an active serious infection at the time of screening (i.e., but not limited to: bacteremia/septicemia, pneumonia, fungal osteomyelitis)
- Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma
- Known hyperprolinemia
- Hypoalbuminemia, protein-losing enteropathies, and any proteinuria
- Allergic reactions to immunoglobulins or other blood products
Show all 14Show fewer
- Known antibodies to Immunoglobulin A (IgA)
- The subject is receiving steroids (oral and parenteral, daily ≥ 0.15 mg of prednisone equivalent/kg/day) or other systemic immunosuppressants
- Female who is pregnant, breast feeding or planning a pregnancy during the course of the study
- Participation in a study with an investigational product other than (IVIG) within 1 month prior to enrollment
- A positive result at screening on any of the following viral markers: Human Immunodeficiency Virus (HIV), Hepatitis C virus (HCV) and Hepatitis B virus (HBV)
- Aspartate aminotransferase (ASAT) or Alanine aminotransferase (ALAT) concentration > 2.5 times the upper normal limit (UNL)
- Creatinine concentration > 1.5 times the UNL
- Any condition that is likely to interfere with evaluation of the study drug or satisfactory conduct of the trial
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Study Site
Atlanta, Georgia, 30322
Study Site
Centennial, Colorado, 80112
Study Site
Dallas, Texas, 75230
Study Site
Fort Wayne, Indiana, 46815
Study Site
Indianapolis, Indiana, 46202
Study Site
Iowa City, Iowa, 52242
Study Site
Los Angeles, California, 90025
Study Site
Los Angeles, California, 90027
Study Site
New York, New York, 10029
Study Site
Newark, New Jersey, 07103
Study Site
North Palm Beach, Florida, 33408
Study Site
Philadelphia, Pennsylvania, 19104
Study Site
St Louis, Missouri, 63104-1095
About this study
Official title: A Phase III Open-Label, Prospective, Multicenter Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human), IgPro20 in Subjects With Primary Immunodeficiency (PID)
The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID).
Read the detailed description
The entire study consists of a 12-week wash-in/wash-out period followed by a 12-month treatment period. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects.
- Conditions
- Primary Immune Deficiency
- Being tested
- Human Normal Immunoglobulin for Subcutaneous Administration
- Keywords
- Immune globulin subcutaneous, SCIG, Primary immunodeficiency, PID
- 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.
Human Normal Immunoglobulin for Subcutaneous AdministrationBiological
Also called Hizentra
| Study group | Role | What they receive |
|---|---|---|
| IgPro20 | Experimental | Human Normal Immunoglobulin for Subcutaneous Administration (IgPro20) is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals. The initial weekly dose was determined based on subjects' previous treatment. Dose adjustments could be performed during the wash-in/wash-out period at the discretion of the investigator. Receives: Biological: Human Normal Immunoglobulin for Subcutaneous Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)
The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days.
Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
Measured: Efficacy period: up to 12 months (week 13 to the completion visit)
Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG)
Evaluate non-inferiority of steady-state IgG area under the concentration-time curves standardized to a 7-day period (sAUCs) for subcutaneous immunoglobulin (SCIG) (IgPro20) versus the sAUC under intravenous immunoglobulin (IVIG) (Privigen) treatment. The sAUC under IVIG was taken from the same subjects in a preceding study (either ZLB03_002CR [NCT00168025] or ZLB05_006CR [NCT00322556]).
Measured: Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment
Secondary outcomes (12)
Annualized Rate of Clinically Documented SBIs (ITT Population)
The annualized rate was based on the total number of SBIs and the total number of subject study days during the study for all subjects in the specified analysis population and adjusted to 365 days.
Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
Measured: For the duration of the study, up to 15 months
Annualized Rate of Clinically Documented SBIs (PPE Population)
The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days.
Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an AE was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
Measured: Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Infection Episodes
The annualized rate was based on the total number of infection episodes occurring during the efficacy period (N = 96) divided by the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Measured: Efficacy period: up to 12 months (week 13 to completion visit)
Number of Infection Episodes (Serious and Non-serious)
Total number of infections for the specified analysis population
Measured: Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
The annualized rate was based on the total number of days out of work / school / kindergarten / day care or inability to perform normal activities due to infection (N = 71), and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Measured: Efficacy period: up to 12 months (week 13 to the completion visit)
Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
Total number of days out of work / school / kindergarten / day care or unable to perform normal daily activities due to infections, for the specified analysis population
Measured: Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Hospitalization Due to Infection
The annualized rate was based on the total number of days of hospitalization due to infection (N = 7) and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.
Measured: Efficacy period: up to 12 months (week 13 to the completion visit)
Number of Days of Hospitalization Due to Infections
Total number of days of hospitalization due to infections for the specified analysis population
Measured: Efficacy period: up to 12 months (week 13 to the completion visit)
Use of Antibiotics for Infection Prophylaxis and Treatment
Annualized rate of days with antibiotics for infection prophylaxis and treatment. The annualized rate was based on the total number of days of antibiotic use for infection prophylaxis and treatment in the efficacy period, and the total number of subject study days for all subjects in the specified analysis population, and adjusted to 365 days.
Measured: Efficacy period: up to 12 months (week 13 to the completion visit)
Total Serum IgG Trough Levels
The IgG trough values per subject were aggregated to a median value, and then median values across subjects were summarized using descriptive statistics.
Measured: Every 4 weeks, throughout the 12-month efficacy period
Maximum Concentration (Cmax) of Total Serum IgG at Steady State
Measured: Week 28 ± 1 week of the treatment period
Tmax at Steady State
Timepoint of maximum concentration (Cmax)
Measured: Week 28 ± 1 week of the treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jan 2007 (estimated)
- Study startNov 2006
- Primary completionOct 2008
- Study completionOct 2008
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 Immune DeficiencyStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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
- Richard L. Wasserman, MD, PhD, Principal investigator, Dallas Allergy Immunology and Medical City Children's Hospital,
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00419341
- Sponsor's protocol ID
- ZLB04_009CR
- Other IDs
- 1458
- Status last verified
- Dec 2012
- First submitted
- 22 Dec 2006
- Last updated
- 25 Jan 2013
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Hagan JB, Fasano MB, Spector S, Wasserman RL, Melamed I, Rojavin MA, Zenker O, Orange JS. Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. J Clin Immunol. 2010 Sep;30(5):734-45. doi: 10.1007/s10875-010-9423-4. Epub 2010 May 8.
PubMed 20454851Wasserman RL, Melamed I, Nelson RP Jr, Knutsen AP, Fasano MB, Stein MR, Rojavin MA, Church JA. Pharmacokinetics of subcutaneous IgPro20 in patients with primary immunodeficiency. Clin Pharmacokinet. 2011 Jun;50(6):405-14. doi: 10.2165/11587030-000000000-00000.
PubMed 21553933
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Open-Label, Prospective, Multicenter Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human), IgPro20 in Subjects With Primary Immunodeficiency (PID)
- ClinicalTrials.gov ID
- NCT00419341
- Acronym / sponsor ID
- ZLB04_009CR
- Conditions
- Primary Immune Deficiency
- Keywords
- Immune globulin subcutaneous, SCIG, Primary immunodeficiency, PID
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- Nov 2006
- Primary completion
- Oct 2008 (actual)
- Study completion
- Oct 2008 (actual)
- First posted
- 8 Jan 2007 (estimated)
- Results
- Posted 25 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID).
Detailed description
The entire study consists of a 12-week wash-in/wash-out period followed by a 12-month treatment period. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IgPro20 | Experimental | Biological: Human Normal Immunoglobulin for Subcutaneous AdministrationHuman Normal Immunoglobulin for Subcutaneous Administration (IgPro20) is a liquid formulation of normal human IgG at a concentration of 20% administered as a SC infusion at weekly intervals. The initial weekly dose was determined based on subjects' previous treatment. Dose adjustments could be performed during the wash-in/wash-out period at the discretion of the investigator. |
Who may qualify
- Ages
- 2 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Male or female aged 2 to 75 years
- Subjects with primary humoral immunodeficiency, namely with a diagnosis of: CVID (Common Variable Immunodeficiency) as defined by PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies) or XLA (X-linked Agammaglobulinemia)
- Written informed consent
Key exclusion criteria (14 listed)
- Newly diagnosed PID
- Evidence of an active serious infection at the time of screening (i.e., but not limited to: bacteremia/septicemia, pneumonia, fungal osteomyelitis)
- Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma
- Known hyperprolinemia
- Hypoalbuminemia, protein-losing enteropathies, and any proteinuria
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 |
|---|---|---|
| Human Normal Immunoglobulin for Subcutaneous AdministrationAlso: Hizentra | Biological | IgPro20 |
Primary outcome
Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population)
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
The annualized rate was based on the total number of SBIs and the total number of subject study days during the efficacy period for all subjects in the specified analysis population and adjusted to 365 days. Potential SBIs included pneumonia, bacteremia/septicemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. If an adverse event (AE) was identified as a potential SBI, the AE was adjudicated by a review committee to determine if the event fulfilled the predefined criteria for SBIs.
Area Under the Concentration-time Curve (AUC) of Total Serum Immunoglobulin G (IgG)
Time frame: Measured during a single dosing interval after at least 12 weeks of stable subcutaneous (SC) dosing with IgPro20 treatment
Evaluate non-inferiority of steady-state IgG area under the concentration-time curves standardized to a 7-day period (sAUCs) for subcutaneous immunoglobulin (SCIG) (IgPro20) versus the sAUC under intravenous immunoglobulin (IVIG) (Privigen) treatment. The sAUC under IVIG was taken from the same subjects in a preceding study (either ZLB03_002CR [NCT00168025] or ZLB05_006CR [NCT00322556]).
12 secondary outcomes
Annualized Rate of Clinically Documented SBIs (ITT Population)
Time frame: For the duration of the study, up to 15 months
Annualized Rate of Clinically Documented SBIs (PPE Population)
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Infection Episodes
Time frame: Efficacy period: up to 12 months (week 13 to completion visit)
Number of Infection Episodes (Serious and Non-serious)
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Number of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Daily Activities Due to Infections
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Annualized Rate of Hospitalization Due to Infection
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Number of Days of Hospitalization Due to Infections
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Use of Antibiotics for Infection Prophylaxis and Treatment
Time frame: Efficacy period: up to 12 months (week 13 to the completion visit)
Total Serum IgG Trough Levels
Time frame: Every 4 weeks, throughout the 12-month efficacy period
Maximum Concentration (Cmax) of Total Serum IgG at Steady State
Time frame: Week 28 ± 1 week of the treatment period
Tmax at Steady State
Time frame: Week 28 ± 1 week of the treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20454851Hagan JB, Fasano MB, Spector S, Wasserman RL, Melamed I, Rojavin MA, Zenker O, Orange JS. Efficacy and safety of a new 20% immunoglobulin preparation for subcutaneous administration, IgPro20, in patients with primary immunodeficiency. J Clin Immunol. 2010 Sep;30(5):734-45. doi: 10.1007/s10875-010-9423-4. Epub 2010 May 8.
- Results publication: PubMed 21553933Wasserman RL, Melamed I, Nelson RP Jr, Knutsen AP, Fasano MB, Stein MR, Rojavin MA, Church JA. Pharmacokinetics of subcutaneous IgPro20 in patients with primary immunodeficiency. Clin Pharmacokinet. 2011 Jun;50(6):405-14. doi: 10.2165/11587030-000000000-00000.
- Related InfoLink provided by the sponsor.
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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.
Richard L. Wasserman, MD, PhD principal investigator
Dallas Allergy Immunology and Medical City Children's Hospital,
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Human Normal Immunoglobulin for Subcutaneous Administration in people with Primary Immune Deficiency, run by CSL Behring at 13 sites in United States.
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 3 inclusion and 14 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 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 25 Jan 2013). 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?
Annualized Rate of Clinically Documented Serious Bacterial Infections (SBIs) (MITT Population) (time frame: Efficacy period: up to 12 months (week 13 to the completion visit)). The study lists 2 primary outcomes in all. 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 NCT00419341, 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 Jan 2013.