Common Variable ImmunodeficiencyPhase 3NCT00542997
Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
A Phase 3 study testing Human Normal Immunoglobulin for Subcutaneous Administration (IGSC) in people with Common Variable Immunodeficiency and X-linked Agammaglobulinemia, run by CSL Behring at 19 sites in 9 countries.
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 65 years
- Conditions the study is for
- Common Variable Immunodeficiency, X-linked Agammaglobulinemia, Autosomal Recessive Agammaglobulinemia
- What is being tested?
- Human Normal Immunoglobulin for Subcutaneous Administration (IGSC)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 19 sitesin 9 countries
- Study dates
- Sep 2007to Aug 2009
- 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 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects with primary humoral immunodeficiency, namely with a diagnosis of Common Variable Immunodeficiency (CVID) as defined by the Pan-American Group for Immunodeficiency (PAGID) and European Society for Immunodeficiencies (ESID), X-linked agammaglobulinemia (XLA) as defined by PAGID and ESID, or Autosomal Recessive Agammaglobulinemia
- Chest X-ray or CT scan obtained within 1 year prior to enrolment
Who cannot join
- Newly diagnosed PID, i.e. subjects who have not previously received immunoglobulin replacement therapy
- Ongoing serious bacterial infection at the time of screening
- Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma
- Allergic or other severe reactions to immunoglobulins or other blood products associated with high anti-IgA
- Additional criteria may apply and examination by an investigator is required to determine eligibility.
Trial locations and contacts
19 sites in 9 countries.
19 sites in 9 countries
Germany7 sites
Study site
Berlin, 13353
Study site
Düsseldorf, 40001
Study site
Freiburg im Breisgau, 79095
Study site
Hanover, 30625
Study site
Leipzig, 04129
Study site
Mainz, 55131
Study site
Munich, 80337
Romania3 sites
Study site
Bucharest, 020393
Study site
Cluj-Napoca, 400162
Study site
Timișoara, 300011
United Kingdom2 sites
Study site
Cardiff, CF 14 4XW
Study site
London, NW3 2QG
About this study
Official title: A Multicentre Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency
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
This study consisted of a 12-week wash-in/wash-out period followed by a 28-week efficacy period. During the 28-week efficacy period, subjects visited the study site at least every 4 weeks for efficacy and safety evaluations and additionally recorded details regarding IgPro20 dose and certain aspects of efficacy and safety in a diary. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects during 1 treatment interval at steady-state (Week 28 ± 1).
- Conditions
- Common Variable Immunodeficiency, X-linked Agammaglobulinemia, Autosomal Recessive Agammaglobulinemia
- Being tested
- Human Normal Immunoglobulin for Subcutaneous Administration (IGSC)
- Keywords
- Subcutaneous immune globulin, SCIG
- Medical subject headings
- Common Variable Immunodeficiency, Bruton type agammaglobulinemia, Agammaglobulinemia, non-Bruton type
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human Normal Immunoglobulin for Subcutaneous Administration (IGSC)Biological
Also called Hizentra, SCIG
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.
| Study group | Role | What they receive |
|---|---|---|
| IgPro20 | Experimental | Not described Receives: Biological: Human Normal Immunoglobulin for Subcutaneous Administration (IGSC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Serum IgG Trough Levels
Total IgG trough levels for IgPro20 treatment at steady state were compared with documented trough level data for IgG treatment received prior to enrolling in the study (either subcutaneous or intravenous IgG). For this purpose, 6 consecutive IgPro20 trough values (obtained prior to infusions 12 to 17) per subject were aggregated to the subject's median value and then median values across subjects were summarised using descriptive statistics. The same procedure was applied to pre-study treatment using the 3 most recent IgG trough values ≥ 5 g/L obtained prior to the first IgPro20 infusion.
Measured: Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment)
Secondary outcomes (6)
Annual Rate of Clinically Documented Serious Bacterial Infections (ITT Population)
Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters.
The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days.
Measured: Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Clinically Documented Serious Bacterial Infections (PPE Population)
Serious bacterial infections (SBIs) included bacterial pneumonia, bacteraemia/septicaemia, osteomyelitis/septic arthritis, bacterial meningitis, and visceral abscess. Diagnosis of the SBIs was based on the presence of predefined clinical signs and symptoms as well as on laboratory parameters.
The annual rate was calculated based on the total number of SBIs and the total number of study days during the efficacy period for all subjects in the PPE population and adjusted to 365 days.
Measured: Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Infection Episodes
The annual rate of episodes was calculated based on the total number of any infection type and the total number of study days during the efficacy period for all subjects in the ITT population and adjusted to 365 days.
Measured: Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections
The annual rate was calculated based on the total number of days out of work/school/kindergarten/day care or unable to perform normal activities due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Measured: Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of the Number of Days of Hospitalization Due to Infections
The annual rate was calculated based on the total number of days of hospitalization due to infections in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Measured: Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Antibiotic Use for Infection Prophylaxis and Treatment
The annual rate was calculated based on the total number of days of antibiotic use in the efficacy period divided by the total number of days in the efficacy period for all subjects and adjusted to 365 days.
Measured: Efficacy period: week 12 to week 40 after study start or to the completion visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2007 (estimated)
- Study startSep 2007
- Primary completionAug 2009
- Study completionAug 2009
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 Common Variable 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- CSL Behring
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Stephen Jolles, MD, Principal investigator, University Hospital of Wales, Cardiff, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00542997
- Sponsor's protocol ID
- 1460
- Other IDs
- ZLB06_001CR
- Status last verified
- Aug 2011
- First submitted
- 11 Oct 2007
- Last updated
- 1 Sep 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Jolles S, Bernatowska E, de Gracia J, Borte M, Cristea V, Peter HH, Belohradsky BH, Wahn V, Neufang-Huber J, Zenker O, Grimbacher B. Efficacy and safety of Hizentra((R)) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy. Clin Immunol. 2011 Oct;141(1):90-102. doi: 10.1016/j.clim.2011.06.002. Epub 2011 Jun 12.
PubMed 21705277Borte M, Pac M, Serban M, Gonzalez-Quevedo T, Grimbacher B, Jolles S, Zenker O, Neufang-Hueber J, Belohradsky B. Efficacy and safety of hizentra(R), a new 20% immunoglobulin preparation for subcutaneous administration, in pediatric patients with primary immunodeficiency. J Clin Immunol. 2011 Oct;31(5):752-61. doi: 10.1007/s10875-011-9557-z. Epub 2011 Jun 15.
PubMed 21674136
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentre Study of the Efficacy, Tolerability, Safety, and Pharmacokinetics of Immune Globulin Subcutaneous (Human) IgPro20 in Subjects With Primary Immunodeficiency
- ClinicalTrials.gov ID
- NCT00542997
- Acronym / sponsor ID
- 1460
- Conditions
- Common Variable Immunodeficiency, X-linked Agammaglobulinemia, Autosomal Recessive Agammaglobulinemia
- Keywords
- Subcutaneous immune globulin, SCIG
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- CSL BehringIndustry (pharma, biotech, devices)
- Study start
- Sep 2007
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 12 Oct 2007 (estimated)
- Results
- Posted 15 Mar 2011
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
This study consisted of a 12-week wash-in/wash-out period followed by a 28-week efficacy period. During the 28-week efficacy period, subjects visited the study site at least every 4 weeks for efficacy and safety evaluations and additionally recorded details regarding IgPro20 dose and certain aspects of efficacy and safety in a diary. Pharmacokinetic (PK) parameters were assessed in a sub-group of subjects during 1 treatment interval at steady-state (Week 28 ± 1).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IgPro20 | Experimental | Biological: Human Normal Immunoglobulin for Subcutaneous Administration (IGSC) |
Who may qualify
- Ages
- 2 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Subjects with primary humoral immunodeficiency, namely with a diagnosis of Common Variable Immunodeficiency (CVID) as defined by the Pan-American Group for Immunodeficiency (PAGID) and European Society for Immunodeficiencies (ESID), X-linked agammaglobulinemia (XLA) as defined by PAGID and ESID, or Autosomal Recessive Agammaglobulinemia
- Chest X-ray or CT scan obtained within 1 year prior to enrolment
Key exclusion criteria (5 listed)
- Newly diagnosed PID, i.e. subjects who have not previously received immunoglobulin replacement therapy
- Ongoing serious bacterial infection at the time of screening
- Malignancies of lymphoid cells such as lymphocytic leukemia, Non-Hodgkin's lymphoma and immunodeficiency with thymoma
- Allergic or other severe reactions to immunoglobulins or other blood products associated with high anti-IgA
- Additional criteria may apply and examination by an investigator is required to determine eligibility.
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 Administration (IGSC)Also: Hizentra, SCIGIgPro20 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. | Biological | IgPro20 |
Primary outcome
Total Serum IgG Trough Levels
Time frame: Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment)
Total IgG trough levels for IgPro20 treatment at steady state were compared with documented trough level data for IgG treatment received prior to enrolling in the study (either subcutaneous or intravenous IgG). For this purpose, 6 consecutive IgPro20 trough values (obtained prior to infusions 12 to 17) per subject were aggregated to the subject's median value and then median values across subjects were summarised using descriptive statistics. The same procedure was applied to pre-study treatment using the 3 most recent IgG trough values ≥ 5 g/L obtained prior to the first IgPro20 infusion.
6 secondary outcomes
Annual Rate of Clinically Documented Serious Bacterial Infections (ITT Population)
Time frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Clinically Documented Serious Bacterial Infections (PPE Population)
Time frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Infection Episodes
Time frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Days Out of Work / School / Kindergarten / Day Care or Unable to Perform Normal Activities Due to Infections
Time frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of the Number of Days of Hospitalization Due to Infections
Time frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
Annual Rate of Antibiotic Use for Infection Prophylaxis and Treatment
Time frame: Efficacy period: week 12 to week 40 after study start or to the completion visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21705277Jolles S, Bernatowska E, de Gracia J, Borte M, Cristea V, Peter HH, Belohradsky BH, Wahn V, Neufang-Huber J, Zenker O, Grimbacher B. Efficacy and safety of Hizentra((R)) in patients with primary immunodeficiency after a dose-equivalent switch from intravenous or subcutaneous replacement therapy. Clin Immunol. 2011 Oct;141(1):90-102. doi: 10.1016/j.clim.2011.06.002. Epub 2011 Jun 12.
- Results publication: PubMed 21674136Borte M, Pac M, Serban M, Gonzalez-Quevedo T, Grimbacher B, Jolles S, Zenker O, Neufang-Hueber J, Belohradsky B. Efficacy and safety of hizentra(R), a new 20% immunoglobulin preparation for subcutaneous administration, in pediatric patients with primary immunodeficiency. J Clin Immunol. 2011 Oct;31(5):752-61. doi: 10.1007/s10875-011-9557-z. Epub 2011 Jun 15.
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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.
Stephen Jolles, MD principal investigator
University Hospital of Wales, Cardiff, UK
19 sites in 9 countries: 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 (IGSC) in people with Common Variable Immunodeficiency and X-linked Agammaglobulinemia, run by CSL Behring at 19 sites in 9 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 2 inclusion and 5 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 1 Sep 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Germany, Romania, Spain, United Kingdom, France and 4 more countries. 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 15 Mar 2011). 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?
Total Serum IgG Trough Levels (time frame: Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment)). 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 NCT00542997, 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 1 Sep 2011.