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| ID | Type | Description | Link |
|---|---|---|---|
| ZLB06_001CR | Other Identifier | CSL Behring |
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The objective of this study is to assess the efficacy, tolerability, safety and pharmacokinetics of IgPro20 in patients with primary humoral immunodeficiency (PID).
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| IgPro20 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Human Normal Immunoglobulin for Subcutaneous Administration (IGSC) | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Concentration (Cmax) of Total Serum IgG | Week 28 (±1week) | |
| Timepoint of Maximum Concentration (Tmax) of Total Serum IgG | Week 28 (±1week) | |
| Area Under the Concentration-Time Curve (AUC_last) of Total Serum IgG |
Inclusion Criteria:
Exclusion Criteria:
Additional criteria may apply and examination by an investigator is required to determine eligibility.
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| Name | Affiliation | Role |
|---|---|---|
| Stephen Jolles, MD | University Hospital of Wales, Cardiff, UK | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Study site | Paris | 75743 | France | |||
| Study site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21705277 | Result | 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. | |
| 21674136 |
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Screening took place 1 to 4 weeks prior to the first IgPro20 infusion.
This multinational study enrolled subjects at 15 of the participating study centers in Europe.
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| ID | Title | Description |
|---|---|---|
| FG000 | IgPro20 (All Treated) | All subjects receiving at least 1 infusion of IgPro20 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Wash in / Wash Out Period |
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| 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. | 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. | 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. | 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. | 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. | Efficacy period: week 12 to week 40 after study start or to the completion visit |
AUC_last = Area under the concentration-time curve until last measured concentration. |
| Week 28 (±1week) |
| Area Under the Concentration-Time Curve (AUCτ) of Total Serum IgG | AUCτ = Area under the concentration-time curve during regular dosing interval; | Week 28 (±1week) |
| Berlin |
| 13353 |
| Germany |
| Study site | Düsseldorf | 40001 | Germany |
| Study site | Freiburg im Breisgau | 79095 | Germany |
| Study site | Hanover | 30625 | Germany |
| Study site | Leipzig | 04129 | Germany |
| Study site | Mainz | 55131 | Germany |
| Study site | Munich | 80337 | Germany |
| Study site | Brescia | 25123 | Italy |
| Study site | Warsaw | 04-736 | Poland |
| Study site | Bucharest | 020393 | Romania |
| Study site | Cluj-Napoca | 400162 | Romania |
| Study site | Timișoara | 300011 | Romania |
| Study site | Barcelona | 08036 | Spain |
| Study site | Seville | 41013 | Spain |
| Study site | Gothenburg | 41685 | Sweden |
| Study site | Bern | 3010 | Switzerland |
| Study site | Cardiff | CF 14 4XW | United Kingdom |
| Study site | London | NW3 2QG | United Kingdom |
| Result |
| Borte 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. |
| COMPLETED |
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| NOT COMPLETED |
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| Efficacy Period |
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| ID | Title | Description |
|---|---|---|
| BG000 | IgPro20 (All Treated) | All subjects enrolled and treated with subcutaneous infusion of IgPro20 |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Number | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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| Type of Primary Immunodeficiency | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Intention-to-treat (ITT) population analysis. The ITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with Week 12). For 2 subjects in the ITT population, the pre-study treatment IgG trough levels were not available. | Posted | Mean | Standard Deviation | g/L | Up to 6 months prior to first IgPro20 treatment (Pre-study treatment) and Week 12 to 17 (IgPro20 treatment) |
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| Secondary | 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. | Intention-to-treat (ITT) population analysis. The ITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with Week 12). | Posted | Number | SBIs/subject/year | Efficacy period: week 12 to week 40 after study start or to the completion visit | Subject Days | Participants |
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| Secondary | 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. | Per Protocol Efficacy (PPE) population analysis. The PPE population included all subjects who completed the 28-week efficacy period according to protocol. | Posted | Number | SBIs/subject/year | Efficacy period: week 12 to week 40 after study start or to the completion visit | Subject Days | Participants |
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| Secondary | 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. | Intention-to-treat (ITT) population analysis. The ITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with Week 12). | Posted | Number | 95% Confidence Interval | episodes/subject/year | Efficacy period: week 12 to week 40 after study start or to the completion visit | Subject Days | Participants |
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| Secondary | 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. | Intention-to-treat (ITT) population analysis. The ITT population included all subjects who were treated with IgPro20 during the efficacy period (starting with Week 12). | Posted | Number | days/subject/year | Efficacy period: week 12 to week 40 after study start or to the completion visit | Subject Days | Participants |
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| Secondary | 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. | ITT population analysis. The intention-to-treat (ITT) data set comprises all subjects treated with the study drug during the efficacy period (week 13 to week 40 after study start or to the completion visit). | Posted | Number | days/subject/year | Efficacy period: week 12 to week 40 after study start or to the completion visit | Subject Days | Participants |
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| Secondary | 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. | ITT population analysis. The intention-to-treat (ITT) data set comprises all subjects treated with the study drug during the efficacy period (week 13 to week 40 after study start or to the completion visit). | Posted | Number | days/subject/year | Efficacy period: week 12 to week 40 after study start or to the completion visit | Subject Days | Participants |
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| Other Pre-specified | Maximum Concentration (Cmax) of Total Serum IgG | Per Protocol Pharmacokinetic (PPK) population analysis. A total of 24 of the 51 enrolled subjects were included in a pharmacokinetic (PK) sub-study. 23 subjects completed the PK sub-study per protocol and were included in the PPK analysis population. | Posted | Mean | Standard Deviation | g/L | Week 28 (±1week) |
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| Other Pre-specified | Timepoint of Maximum Concentration (Tmax) of Total Serum IgG | Per Protocol Pharmacokinetic (PPK) population analysis. A total of 24 of the 51 enrolled subjects were included in a pharmacokinetic (PK) sub-study. 23 subjects completed the PK sub-study per protocol and were included in the PPK analysis population. | Posted | Median | Full Range | day | Week 28 (±1week) |
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| Other Pre-specified | Area Under the Concentration-Time Curve (AUC_last) of Total Serum IgG | AUC_last = Area under the concentration-time curve until last measured concentration. | Per Protocol Pharmacokinetic (PPK) population analysis. A total of 24 of the 51 enrolled subjects were included in a pharmacokinetic (PK) sub-study. 23 subjects completed the PK sub-study per protocol and were included in the PPK analysis population. | Posted | Mean | Standard Deviation | day x g/L | Week 28 (±1week) |
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| Other Pre-specified | Area Under the Concentration-Time Curve (AUCτ) of Total Serum IgG | AUCτ = Area under the concentration-time curve during regular dosing interval; | Per Protocol Pharmacokinetic (PPK) population analysis. A total of 24 of the 51 enrolled subjects were included in a pharmacokinetic (PK) sub-study. 23 subjects completed the PK sub-study per protocol and were included in the PPK analysis population. 7 subjects were missing data for AUCτ. | Posted | Mean | Standard Deviation | day x g/L | Week 28 (±1week) |
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The observation period for adverse events was from the time the subjects had given informed consent until they had the final examination (completion visit up to 40 weeks) or extended when serious adverse events were reported.
A total of 1831 infusions of IgPro20 were administered to 51 subjects during the course of the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | IgPro20 (All Treated) | All subjects receiving at least 1 infusion of IgPro20 | 5 | 51 | 50 | 51 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Bronchiolitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Sciatica | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 12.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Injection site reaction | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Infusion site pain | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Injection site pruritus | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Injection site swelling | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Acute sinusitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Conjunctivitis | Eye disorders | MedDRA 12.0 | Systematic Assessment |
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| Erythema | Skin and subcutaneous tissue disorders | MedDRA 12.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Infusion site haematoma | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 12.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 12.0 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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| Rhinitis | Infections and infestations | MedDRA 12.0 | Systematic Assessment |
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The investigator must provide a copy of any results communication to the sponsor for review at least 30 days prior to public release. The sponsor may request any changes necessary to prevent forfeiture of patent rights to data not in the public domain. For a multi-center study, the investigator must wait (i) at least 1 year after the study is completed at all sites or (ii) until notified by the sponsor that no multi-center publication is planned before seeking publication review.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Program Director, Clinical R&D | CSL Behring | Use email contact | clinicaltrials@cslbehring.com |
| ID | Term |
|---|---|
| D017074 | Common Variable Immunodeficiency |
| C537409 | Bruton type agammaglobulinemia |
| C538056 | Agammaglobulinemia, non-Bruton type |
| ID | Term |
|---|---|
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D005719 | gamma-Globulins |
| C558471 | Hizentra |
| ID | Term |
|---|---|
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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| 16 to < 65 years |
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| Autosomal recessive agammaglobulinemia (ARAG) |
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