Immunologic Deficiency Syndrome
Conditions
Keywords
Primary immune deficiency
Brief summary
This study will compare the blood level of Gamunex in patients. Patients will take it as an injection under the skin or in a vein. The study will compare how safe and tolerable the two methods are in the patients. The patients in this study have a defect in their immune system from a genetic cause.
Detailed description
This is an open-label, single-sequence, multi-center trial with subjects previously diagnosed with primary immune deficiency. Subjects will be on IGIV until a steady state is reached at which time PK profiling during the IV phase will occur. Subjects will begin SC administration 1 week following last IV dose and followed for a period of six months. PK profiling in SC phase will occur when subject reaches approximate steady-state on SC administration.
Interventions
BIOLOGICALImmune Globulin Intravenous (Human)
This trial was an open-label, single-sequence, study. The enrolled subjects received IGIV-C via two routes of administration (IV for 4 -5 weeks and SC for 24 weeks) in order to compare the PK variables, safety and tolerability of SC administration of IGIV-C. Certain subjects required IV IGIV-C dosing during a Run-in Phase (3 - 4 months) for steady-state conditions prior to the IV phase. Subjects received two IV infusions of IGIV (between 200 - 600 mg based on the subject's previous IgG dosing regimen, 3 to 4 weeks apart) until a steady-state was reached at which time PK profiling was performed. Subjects began weekly SC administration (1.37 times the weekly equivalency of each subject's monthly IV dose) 1 week following last IV dose and followed for a period of six months.
Sponsors
Grifols Therapeutics LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adults and adolescents (age 13-75 inclusive) with a documented and confirmed pre-existing diagnosis of chronic primary immunodeficiency * Previously or currently on IgG replacement therapy * Documented (within 3 months) plasma IgG level of ≥500 mg/dL on current IgG therapy (IgG level can be obtained at the screening visit if documentation is not available) * The medical records for all subjects within the previous 2 years should be available to document previous infections and treatment
Exclusion criteria
* Clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with successful completion of the trial * The subject has a known adverse reaction to Gamunex or other blood products * The subject has a history of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections or other disorders where subcutaneous therapy would be contraindicated * The subject has known selective IgA deficiency with the exception of a known selective IgA deficient subject who has no previous documented eventful reaction to products containing IgA * The subject is pregnant or lactating * The subject has significant proteinuria and/or has a history of acute renal failure and/or severe renal impairment (BUN or creatinine more than 2.5 times the upper limit of normal) and/or on dialysis * The subject has known substance or prescription drug abuse in the past 12 months * The subject has a history of or current diagnosis of deep venous thrombosis * The subject has an acquired medical condition that is known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (absolute neutrophil count less than 1000 x 10e6/L), or HIV infection/AIDS * The subject is receiving any of the following medications: corticosteroids (long-term daily, \>1 mg of prednisone equivalent/kg/day for \>30 days) (intermittent courses would not exclude subject); immunosuppressants; or immunomodulators * The subject has non-controlled arterial hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg) * The subject has anemia (hemoglobin \<10 g/dL) at screening * The subject has participated in another clinical trial within 30 days prior to screening (imaging studies without investigative treatments are permitted) or has received any investigational blood product within the previous 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Least Square Means of Area Under the Curve (AUC) for Plasma Total Immunoglobulin G (IgG) | IV Phase (21 or 28 days) at IV Visit #1, pre- and post-dose: 0 hr., 1 hr., and 1, 2, 3, 5, 7, 14, 21, and 28 days; SC Phase at Week #17, pre- and post-dose: 0 hr., and 1, 3, 4, 5, and 7 days | Geometric least-squares mean of steady-state plasma concentration of total IgG vs. time profile (AUC). |
Countries
Canada, United States
Participant flow
Recruitment details
First Patient, First Visit: Nov. 21, 2006, Last patient, Last visit: Aug. 26, 2008. This study was performed at medical clinics.
Participants by arm
| Arm | Count |
|---|---|
| Safety Population The safety population included all subjects who received any amount of study medication (IGIV-C) via intravenous (IV) and/or subcutaneous (SC) routes of administration. As such, the safety population included all study participants combined (who received any dose), whether they entered the study in the Run-In or Intravenous Phase. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Run-In Phase | Adverse Event | 1 |
| Run-In Phase | Lost to Follow-up | 1 |
| Run-In Phase | Withdrawal by Subject | 1 |
| Subcutaneous Phase | Adverse Event | 2 |
| Subcutaneous Phase | Lost to Follow-up | 1 |
| Subcutaneous Phase | Non-compliance with study medication | 2 |
| Subcutaneous Phase | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Categorical <=18 years | 3 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age, Continuous | 42.5 years STANDARD_DEVIATION 15.8 |
| Region of Enrollment Canada | 9 participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 21 | 9 / 32 | 29 / 32 |
| serious Total, serious adverse events | 2 / 21 | 0 / 32 | 1 / 32 |
Outcome results
Primary
Geometric Least Square Means of Area Under the Curve (AUC) for Plasma Total Immunoglobulin G (IgG)
Geometric least-squares mean of steady-state plasma concentration of total IgG vs. time profile (AUC).
Time frame: IV Phase (21 or 28 days) at IV Visit #1, pre- and post-dose: 0 hr., 1 hr., and 1, 2, 3, 5, 7, 14, 21, and 28 days; SC Phase at Week #17, pre- and post-dose: 0 hr., and 1, 3, 4, 5, and 7 days
Population: A total of 32 subjects in the IV phase and 26 subjects in the SC phase had sufficient plasma concentration of total IgG vs. time profiles (AUC) for assessment of steady-state PK parameters.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Gamunex Intravenous (IV) Administration | Geometric Least Square Means of Area Under the Curve (AUC) for Plasma Total Immunoglobulin G (IgG) | 7549 mg*hr/ml | Standard Deviation 1217 |
| Gamunex Subcutaneous (SC) Administration | Geometric Least Square Means of Area Under the Curve (AUC) for Plasma Total Immunoglobulin G (IgG) | 6706 mg*hr/ml | Standard Deviation 1241 |
Comparison: The IV phase was considered as the Reference study phase and the SC phase as the Test study phase. The ANOVA included calculation of least-squares means (LSM), differences between adjusted means and the standard error associated with these differences.90% CI: [0.861, 0.917]ANOVA