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Safety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)

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ClinicalTrials.gov Identifier: NCT00322556
Recruitment Status : Completed
First Posted : May 8, 2006
Results First Posted : October 26, 2012
Last Update Posted : October 26, 2012
Sponsor:
Information provided by (Responsible Party):
CSL Behring

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Agammaglobulinemia
IgG Deficiency
Common Variable Immunodeficiency
Intervention Drug: Immunoglobulins Intravenous (Human)
Enrollment 55
Recruitment Details  
Pre-assignment Details  
Arm/Group Title IgPro10
Hide Arm/Group Description A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
Period Title: Overall Study
Started 55
Completed 43
Not Completed 12
Reason Not Completed
Adverse Event             1
Withdrawal by Subject             1
Lost to Follow-up             3
Other Reason             7
Arm/Group Title IgPro10
Hide Arm/Group Description A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
Overall Number of Baseline Participants 55
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 55 participants
30  (21)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 55 participants
3 to < 12 years 13
12 to < 16 years 8
16 to < 65 years 30
>= 65 years 4
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 55 participants
Female
29
  52.7%
Male
26
  47.3%
1.Primary Outcome
Title The Proportion of Infusions With One or More Temporally-associated Adverse Events (AEs).
Hide Description AEs were considered temporally-associated AEs if they occurred during the infusion or in the period from the start of the infusion until either 48 or 72 hours after the end of the infusion.
Time Frame During each infusion, and within 48 or 72 hours after the end of each infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Data Set (SDS) comprised all subjects treated with the study drug.
Arm/Group Title IgPro10
Hide Arm/Group Description:
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
Overall Number of Participants Analyzed 55
Overall Number of Units Analyzed
Type of Units Analyzed: Infusions
771
Measure Type: Number
Unit of Measure: Proportion of infusions
During infusion 0.073
Within 48 hours after infusion 0.141
Within 72 hours after infusion 0.150
2.Primary Outcome
Title Influence of Infusion Rate on Temporally-Associated AEs
Hide Description

The total and most frequent (1% or more) number of infusions for which subjects experienced temporally-associated AEs occurring within 72 hours of infusion, by infusion rate (≤ 4 mg/kg/min, ≤ 8 mg/kg/min, and > 8 and ≤ 12 mg/kg/min).

AEs were considered to be temporally-associated AEs if they occurred in the period from the start of the infusion until 72 hours after the end of the infusion.

Time Frame Within 72 hours after each infusion
Hide Outcome Measure Data
Hide Analysis Population Description
'New subjects’ could receive IgPro10 at up to 4 mg/kg/min. 'Old' subjects (ie, those treated with the study drug who participated in a preceding, pivotal, Phase III clinical study with intravenous IgPro10 [study number ZLB03_002CR, NCT00168025]), could receive IgPro10 at up to 12 mg/kg/min at the discretion of the Investigator.
Arm/Group Title IgPro10 (≤ 4 mg/kg/Min) IgPro10 (≤ 8 mg/kg/Min) IgPro10 (> 8 to ≤ 12 mg/kg/Min)
Hide Arm/Group Description:
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study, at the maximum infusion rate (≤ 4 mg/kg/min) for new subjects.
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study, at the low maximum infusion rate (≤ 8 mg/kg/min) for old subjects.
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study, at the high maximum infusion rate (> 8 and ≤ 12 mg/kg/min) for old subjects.
Overall Number of Participants Analyzed 10 22 23
Overall Number of Units Analyzed
Type of Units Analyzed: Infusions
81 423 265
Measure Type: Number
Unit of Measure: Infusions
All temporally-associated AEs 23 153 30
Headache 10 54 2
Pyrexia 0 9 1
Nausea 0 8 2
Back pain 0 8 0
Chills 0 7 0
Pain 0 6 0
Anaemia 1 0 0
Constipation 2 0 0
Fatigue 3 0 0
Influenza like illness 3 1 0
Myalgia 1 0 0
Pharyngolaryngeal pain 1 1 2
Eczema 1 0 0
Night sweats 1 0 0
3.Primary Outcome
Title Rate of AEs by Severity and Relationship
Hide Description

The AE rate was the number of AEs over the number of infusions administered.

Mild AEs: Did not interfere with daily activities; Moderate AEs: Interfered with routine daily activities; Severe AEs: Impossible to perform routine daily activities.

At least possibly related AEs included possibly related AEs, probably related AEs, and related AEs.

Time Frame For the duration of the study, up to approximately 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
The SDS comprised all subjects treated with the study drug.
Arm/Group Title IgPro10
Hide Arm/Group Description:
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
Overall Number of Participants Analyzed 55
Overall Number of Units Analyzed
Type of Units Analyzed: Infusions
771
Measure Type: Number
Unit of Measure: AEs per infusion
All mild AEs 0.467
All moderate AEs 0.280
All severe AEs 0.058
Unrelated AEs 0.610
Possibly related AEs 0.088
Probably related AEs 0.048
Related AEs 0.060
At least possibly related mild AEs 0.121
At least possibly related moderate AEs 0.062
At least possibly related severe AEs 0.013
Unrelated mild AEs 0.346
Unrelated moderate AEs 0.218
Unrelated severe AEs 0.045
4.Primary Outcome
Title Number of Subjects With Clinically Significant Changes in Vital Signs.
Hide Description Vital signs included heart rate, systolic blood pressure, diastolic blood pressure, and body temperature.
Time Frame Before, during, and after each infusion.
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Data Set (SDS) comprised all subjects treated with the study drug.
Arm/Group Title IgPro10
Hide Arm/Group Description:
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
Overall Number of Participants Analyzed 55
Measure Type: Number
Unit of Measure: Participants
0
5.Secondary Outcome
Title Annualized Rate of Acute Serious Bacterial Infections.
Hide Description

The annualized rate was based on the total number of infections and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

Acute serious bacterial infections included pneumonia, bacteremia / septicemia, osteomyelitis / septic arthritis, bacterial meningitis, and visceral abscess.

Time Frame For the duration of the study, up to approximately 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
The Intention-To-Treat (ITT) data set comprised all subjects treated with the study drug
Arm/Group Title IgPro10
Hide Arm/Group Description:
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
Overall Number of Participants Analyzed 55
Overall Number of Units Analyzed
Type of Units Analyzed: Subject Study Days
20757
Measure Type: Number
Unit of Measure: Infections per subject year
0.018
6.Secondary Outcome
Title Number of Days Out of Work / School / Kindergarten / Day Care or Inability to Perform Normal Activities Due to Illness.
Hide Description [Not Specified]
Time Frame For the duration of the study, up to approximately 29 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT data set comprised all subjects treated with the study drug. The patient diary (in which the number of days was recorded) was not available for 1 subject so the analyzed population was reduced from 55 to 54 subjects for this outcome measure.
Arm/Group Title IgPro10
Hide Arm/Group Description:
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
Overall Number of Participants Analyzed 54
Median (Full Range)
Unit of Measure: Days
8.5
(0.0 to 104.0)
7.Secondary Outcome
Title Number of Days of Hospitalization.
Hide Description [Not Specified]
Time Frame For the duration of the study, up to approximately 29 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT data set comprised all subjects treated with the study drug. The patient diary (in which the number of days was recorded) was not available for 1 subject so the analyzed population was reduced from 55 to 54 subjects for this outcome measure.
Arm/Group Title IgPro10
Hide Arm/Group Description:
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
Overall Number of Participants Analyzed 54
Median (Full Range)
Unit of Measure: Days
0.0
(0.0 to 17.0)
8.Secondary Outcome
Title Annualized Rate of Any Infection.
Hide Description

The annualized rate was based on the total number of infections and the total number of subject study days for all subjects in the specified analysis population and adjusted to 365 days.

Infections were classified as all AEs with the system organ class “infections and infestations” and AEs with the preferred term “conjunctivitis”.

Time Frame For the duration of the study, up to approximately 29 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT data set comprised all subjects treated with the study drug.
Arm/Group Title IgPro10
Hide Arm/Group Description:
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
Overall Number of Participants Analyzed 55
Overall Number of Units Analyzed
Type of Units Analyzed: Subject Study Days
20757
Measure Type: Number
Unit of Measure: Infections per subject year
1.600
9.Secondary Outcome
Title Trough Levels of Total Immunoglobulin (IgG) Serum Concentrations.
Hide Description Mean IgG trough concentration. For this analysis, each subject’s values were first aggregated to their median and the median values were then analyzed.
Time Frame Prior to each infusion; every 3 or 4 weeks depending upon the dosing schedule.
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT data set comprised all subjects treated with the study drug for which serum IgG information was available.
Arm/Group Title IgPro10
Hide Arm/Group Description:
A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
Overall Number of Participants Analyzed 54
Mean (Full Range)
Unit of Measure: g/L
9.72
(5.72 to 18.01)
Time Frame For the duration of the study, up to approximately 29 months
Adverse Event Reporting Description Only AEs starting at or after the first study drug infusion were included. The SDS comprised all subjects treated with the study drug.
 
Arm/Group Title IgPro10
Hide Arm/Group Description A 10% liquid formulation of human immunoglobulin G (stabilized with 250 millimole per liter of L-proline) administered as an intravenous infusion, every 3 or 4 weeks for the duration of the study.
All-Cause Mortality
IgPro10
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
IgPro10
Affected / at Risk (%) # Events
Total   11/55 (20.00%)    
Blood and lymphatic system disorders   
Splenomegaly  1  1/55 (1.82%)  1
Gastrointestinal disorders   
Gastrointestinal hemorrhage  1  1/55 (1.82%)  1
Small intestinal obstruction  1  1/55 (1.82%)  2
Intestinal obstruction  1  1/55 (1.82%)  1
Infections and infestations   
Clostridial infection  1  1/55 (1.82%)  1
Giardiasis  1  1/55 (1.82%)  1
Pneumonia  1  1/55 (1.82%)  1
Sinusitis  1  1/55 (1.82%)  1
Cellulitis  1  1/55 (1.82%)  1
Otitis externa fungal  1  1/55 (1.82%)  1
Musculoskeletal and connective tissue disorders   
Muscular weakness  1  1/55 (1.82%)  1
Joint effusion  1  1/55 (1.82%)  1
Nervous system disorders   
Transient ischemic attack  1  1/55 (1.82%)  1
Psychiatric disorders   
Aggression  1  1/55 (1.82%)  1
Skin and subcutaneous tissue disorders   
Angioedema  1  1/55 (1.82%)  1
Surgical and medical procedures   
Ileostomy closure  1  1/55 (1.82%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IgPro10
Affected / at Risk (%) # Events
Total   48/55 (87.27%)    
Ear and labyrinth disorders   
Ear pain  1  3/55 (5.45%)  4
Eye disorders   
Conjunctivitis  1  3/55 (5.45%)  3
Gastrointestinal disorders   
Nausea  1  11/55 (20.00%)  16
Diarrhea  1  10/55 (18.18%)  13
Vomiting  1  8/55 (14.55%)  12
Abdominal pain  1  3/55 (5.45%)  4
Abdominal pain upper  1  3/55 (5.45%)  5
Toothache  1  3/55 (5.45%)  3
General disorders   
Pyrexia  1  8/55 (14.55%)  22
Fatigue  1  5/55 (9.09%)  9
Pain  1  5/55 (9.09%)  10
Chest pain  1  3/55 (5.45%)  4
Chills  1  3/55 (5.45%)  7
Influenza-like illness  1  3/55 (5.45%)  9
Infections and infestations   
Sinusitis  1  14/55 (25.45%)  15
Upper respiratory tract infection  1  6/55 (10.91%)  6
Nasopharyngitis  1  5/55 (9.09%)  5
Pneumonia  1  3/55 (5.45%)  3
Bronchitis  1  3/55 (5.45%)  3
Gastroenteritis viral  1  3/55 (5.45%)  5
Injury, poisoning and procedural complications   
Joint sprain  1  3/55 (5.45%)  5
Procedural pain  1  3/55 (5.45%)  3
Musculoskeletal and connective tissue disorders   
Back pain  1  6/55 (10.91%)  12
Nervous system disorders   
Headache  1  21/55 (38.18%)  147
Dizziness  1  4/55 (7.27%)  4
Psychiatric disorders   
Insomnia  1  4/55 (7.27%)  4
Respiratory, thoracic and mediastinal disorders   
Cough  1  12/55 (21.82%)  17
Pharyngolaryngeal pain  1  9/55 (16.36%)  11
Epistaxis  1  5/55 (9.09%)  9
Rhinorrhea  1  4/55 (7.27%)  5
Asthma  1  3/55 (5.45%)  4
Skin and subcutaneous tissue disorders   
Eczema  1  6/55 (10.91%)  6
Rash  1  6/55 (10.91%)  7
Urticaria  1  3/55 (5.45%)  4
Vascular disorders   
Hypertension  1  4/55 (7.27%)  6
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
CSL agreements and restrictions on publishing may vary with individual investigators; however, CSL will not prohibit any investigator from publishing. CSL supports the publication of results from all centers of a multi-center trial and generally requires that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trial Disclosure Manager
Organization: CSL Behring
Phone: Use email contact
EMail: clinicaltrials@cslbehring.com
Layout table for additonal information
Responsible Party: CSL Behring
ClinicalTrials.gov Identifier: NCT00322556     History of Changes
Other Study ID Numbers: ZLB05_006CR
First Submitted: May 5, 2006
First Posted: May 8, 2006
Results First Submitted: September 27, 2012
Results First Posted: October 26, 2012
Last Update Posted: October 26, 2012