Common Variable Hypogammaglobulinemia, Hypogammaglobulinemia, Immunodeficiency With Hyper-IgM, Primary Immunodeficiency, Wiskott-Aldrich Syndrome, X-linked Hypogammaglobulinemia
Conditions
Keywords
Primary Antibody Deficiency, Common variable hypogammaglobulinemia, X-linked hypogammaglobulinemia, Hypogammaglobulinemia, Immunodeficiency with hyper-IgM, Wiskott-Aldrich Syndrome
Brief summary
The main objective of this study is to see if GAMMAPLEX is efficacious with respect to Food and Drug Administration (FDA) minimal requirements (no more than 1 serious, acute, bacterial infection per subject per year) in subjects with Primary Immunodeficiency Diseases (PID). The secondary objectives are to assess the safety and tolerability of GAMMAPLEX and to determine if GAMMAPLEX has a pharmacokinetic (PK) profile comparable with that of intact Immunoglobulin G (IgG) in subjects with PID.
Detailed description
Primary Efficacy Variable The primary variable is the number of serious, acute, bacterial infections/subject/year, and it will be based on the total of all of the following events as defined by the FDA: bacterial Pneumonia, bacteremia/sepsis, osteomyelitis/septic arthritis, visceral abscess, and bacterial meningitis. Secondary Efficacy Variables Secondary efficacy will be determined by using the following variables: number of days of work/school missed because of infection per subject year; number and days of hospitalizations because of infection per subject year; number of visits to physicians for acute problems and/or number of visits to hospital emergency rooms per subject year; other infections documented by fever or a positive result on a radiograph and/or culture; number of infectious episodes per subject per year; number of days on therapeutic antibiotics.These data will be entered into the subject diary, confirmed by the physician, and entered on the electronic-CRF (e-CRF). Safety Variables. The variables used to assess safety will be the following: adverse events (AEs); vital signs; clinical laboratory tests and Direct Coombs' Test; transmission of viruses; physical examination. Test product, dose/mode of administration, batch number(s): The GAMMAPLEX dose is 300-800 mg/kg/infusion (milligram per killgram per infusion) every 21 or 28 days, intravenously. At least 2 batches will be used in this study and no more than 1 batch in any given infusion. Duration of treatment: The total duration of treatment is 12 months.
Interventions
BIOLOGICALGammaplex (Intravenous immunoglobulin)
GAMMAPLEX 5g/100 mL, dose is 300-800 mg/kg/infusion every 21 or 28 days, intravenously for 12 months.
Sponsors
Bio Products Laboratory
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. The subject is 3 years of age or older, of either sex, belonging to any ethnic group, and above a minimum weight of 27.5 kg. This weight is based on the amount of blood required for testing. If subject is participating in the PK segment, the minimum weight required is 37 kg. 2\. The subject has a primary immunodeficiency disease, which has as a significant component of hypogammaglobulinemia and/or antibody deficiency (e.g. (exempli gratia / for example), common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-immunoglobulin M (hyper-IgM) syndrome, Wiskott-Aldrich Syndrome). Isolated deficiency of a single IgG subclass, or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion. 3\. The subject has been receiving licensed or investigational (Phase III or IIIb) immunoglobulin intravenous (IGIV) replacement therapy at a dose that has not changed by + 50% of the mean dose for at least 3 months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be between 21 and 28 days inclusive. The subject must have maintained a trough level at least 300 mg/dL (milligram per decilitre) above baseline serum IgG levels (defined as before initiation of any gamma globulin treatment for that subject). The trough level must be 600 mg/dL. 4\. Trough levels of IgG and dose of IGIV, treatment intervals, and the trade name of the IGIV treatments used for the last 2 consecutive routine (licensed or investigational product) must be documented for each subject before the first infusion in this study can be administered. 5\. If a subject is a female of child-bearing potential, she must have a negative result on an Human Chorionic Gonadotrophin (HCG)-based pregnancy test. 6\. If a subject is a female who is or becomes sexually active, she must practice contraception by using a method of proven reliability for the duration of the study. 7\. The subject is willing to comply with all aspects of the protocol, including blood sampling, for the duration of the study. 8\. The subject has signed an informed consent form (if at least 18 years old) or the subject's parent or legal guardian has signed the informed consent form. If appropriate, the subject has signed a child assent form (See Section 12.3).
Exclusion criteria
* Subjects will be excluded if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease. | 12 months | By assessing the number of serious, acute, bacterial infections per subject per year in subjects with Primary Immunodeficiency disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Pharmacokinetic (PK) Half-Life of Immunoglobulin G (IgG) | -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days | Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment. |
| The Pharmacokinetic (PK) Clearance of Immunoglobulin G (IgG) | -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days | Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment. |
| The Pharmacokinetic (PK) Volume of Distribution (Vz)of Immunoglobulin G (IgG) | -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days | Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment. |
| The Pharmacokinetic (PK) Mean Residence Time (MRT) for Inmuunoglobulin G (IgG) | -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days | Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment. |
Countries
United States
Participant flow
Recruitment details
First enrollment: 06 February 2006 Last subject completed: 06 November 2007 Seven investigative sites, all hospital clinics
Pre-assignment details
This was an open study. All enrolled subjects received study medication.
Participants by arm
| Arm | Count |
|---|---|
| Gammaplex All subjects received between 300 to 800 mg/kg/infusion of Gammaplex intravenously, every 21 day or 28 days. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Gammaplex |
|---|---|
| Age, Categorical <=18 years | 6 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants |
| Age Continuous | 44.0 years STANDARD_DEVIATION 19.1 |
| Region of Enrollment United States | 50 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 47 / 50 |
| serious Total, serious adverse events | 6 / 50 |
Outcome results
Primary
Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease.
By assessing the number of serious, acute, bacterial infections per subject per year in subjects with Primary Immunodeficiency disease.
Time frame: 12 months
Population: Intent to Treat (ITT).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gammaplex | Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease. | 0 SABIs/subject/year |
Comparison: The estimated serious acute bacterial infection (SABI) rate was calculated by dividing no. of infections by no.of subject years. The exponential of the upper limit of the 98% 2-sided Confidence Interval (CI) gave the upper, 1-sided, 99% confidence bound, estimated using Poisson regression. The equivalent upper bound per subject year was obtained by dividing this figure by total subject years.p-value: 0.0199% CI: [0, 0.101]Poisson regression with log link
Secondary
The Pharmacokinetic (PK) Clearance of Immunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Time frame: -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days
Population: Only 24 of the 45 evaluable subjects participated in the Pharmacokinetic part of the protocol. No data imputation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gammaplex | The Pharmacokinetic (PK) Clearance of Immunoglobulin G (IgG) | 0.585 mL/day/kg | Standard Deviation 0.2508 |
Secondary
The Pharmacokinetic (PK) Half-Life of Immunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Time frame: -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days
Population: Only 24 of the 45 evaluable subjects participated in the Pharmacokinetic part of the protocol. No data imputation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gammaplex | The Pharmacokinetic (PK) Half-Life of Immunoglobulin G (IgG) | 41.19 Days | Standard Deviation 19.19 |
Secondary
The Pharmacokinetic (PK) Mean Residence Time (MRT) for Inmuunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Time frame: -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gammaplex | The Pharmacokinetic (PK) Mean Residence Time (MRT) for Inmuunoglobulin G (IgG) | 56.1 Days | Standard Deviation 23.06 |
Secondary
The Pharmacokinetic (PK) Volume of Distribution (Vz)of Immunoglobulin G (IgG)
Blood samples for PK analysis were obtained and analysed at 10 different time points, i.e. -5, 0, 60 minutes (min), 24, 48 hours (hrs), 4, 7, 14, 21 and 28 days, at an infusion visit following 6 months of treatment.
Time frame: -5, 0, 60 min, 24, 48 hrs, 4, 7, 14, 21 and 28 days
Population: Only 24 of the 45 evaluable subjects participated in the Pharmacokinetic part of the protocol. No data imputation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gammaplex | The Pharmacokinetic (PK) Volume of Distribution (Vz)of Immunoglobulin G (IgG) | 0.297 dL/kg | Standard Deviation 0.0539 |