A Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Immune Globulin (Human) 10% (Gamunex-C) PEG Process (IVIG-PEG) Compared to Gamunex-C in Participants With Primary Humoral Immunodeficiency
Study Details
Study Description
Brief Summary
The purpose of this study is to demonstrate bioequivalence of IVIG-PEG with Gamunex-C (IVIG-C) at steady-state as determined by comparing total Immunoglobulin G (IgG) area under the concentration-time curve during the defined dosing interval ([AUC0-τ] either every 3 weeks [AUC0-21 days] or every 4 weeks [AUC0-28 days]) and maximum concentration in a dosing interval (Cmax) in participants diagnosed with primary humoral immunodeficiency (PI) currently receiving chronic IVIG replacement treatment.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Gamunex-C Participants will receive Gamunex-C by means of an infusion pump at an individualized dose (based on historical IVIG treatment dose) between 200 to 800 mg/kg per infusion at an infusion rate of 1 mL/kg/min or up to 8 mL/kg/min depending on participant tolerance. The subject's usual mg/kg dose (given on either a 3 or 4 week repeating schedule) will be the same mg/kg dose and schedule that the subject was receiving prior to entering screening. This mg/kg dose and schedule will be used throughout the study duration. Note that the weight of the subject will be measured at each visit and if the subject's weight changes, the actual weight at each visit will be used to calculate amount of drug (mg) to be administered. Gamunex-C will be administered every 3 weeks or 4 weeks for at least 6 or 5 doses for an approximate maximum duration of up to 6 months. |
Biological: Gamunex-C
Intravenous infusion.
Other Names:
|
| Experimental: IVIG-PEG Following treatment with Gamunex-C, participants will receive IVIG-PEG by means of an infusion pump at an equivalent dose between 200 to 800 mg/kg per infusion at an infusion rate of 1 mL/kg/min or up to 8 mL/kg/min depending on participant tolerance. IVIG-PEG will be administered every 3 weeks or 4 weeks for at least 6 or 5 doses for an approximate maximum duration of up to 6 months. |
Biological: IVIG-PEG
Intravenous infusion.
|
Outcome Measures
Primary Outcome Measures
- Area Under the Concentration Time Curve Over a Regular Dosing Interval of Every 3 Weeks (AUC0-21) [Pre-dose, within 10 minutes of last infusion completion, 1, 3, 6, 24, 48 hours, 4, 7, 14 and 21 days post-infusion (up to 3 weeks)]
- Area Under the Concentration Time Curve Over a Regular Dosing Interval of Every 4 Weeks (AUC0-28) [Pre-dose, within 10 minutes of last infusion completion, 1, 3, 6, 24, 48 hours, 4, 7, 14, 21 and 28 days post-infusion (up to 4 weeks)]
- Maximum Concentration in a Dosing Interval (Cmax) [Pre-dose, within 10 minutes of last infusion completion, 1, 3, 6, 24, 48 hours, 4, 7, 14, 21 and 28 days post-infusion (up to 4 weeks)]
Secondary Outcome Measures
- Rate of Serious Bacterial Infections (SBIs) [Baseline up to Week 54]
- Number of Participants with Any kind of Infection [Baseline up to Week 54]
- Number of Days on Antibiotics [Baseline up to Week 54]
- Number of Hospitalizations due to Infection [Baseline up to Week 54]
- Number of Days of Work/School/Daily Activities Missed per Participant per year due to Infections and Their Treatment [Baseline up to Week 54]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female between 18 and 75 years of age (inclusive) at Screening
-
Documented and confirmed pre-existing diagnosis of PI with features of hypogammaglobulinemia requiring IV IgG replacement therapy including but not limited to the following humoral-based immunodeficiency syndromes (example, X-linked agammaglobulinemia, common variable immunodeficiency), and combined immunodeficiency syndromes without lymphocytopenia (example, hyper immunoglobulin M [IgM] immunodeficiency syndrome).
-
IgG trough level ≥500 milligrams per deciliter (mg/dL) at screening visit. Note: Patients entering Group 1 must additionally have trough levels ≥500 mg/dL documented within the previous year. For patients entering Group 2, if Screening trough levels are not ≥500 mg/dL, the subject will be a Screen Failure, but may be rescreened following dose adjustment of their original IV IgG replacement therapy regimen and recording an IgG trough level ≥500 mg/dL
-
Has not had an SBI within the last 6 months prior to screening or during the screening phase.
-
Medical records are available to document diagnosis, previous infections, and treatment.
-
Willing to comply with all aspects of the study protocol, including blood sampling, for the duration of the study.
-
Signed and dated a written informed consent form (ICF) confirming his or her willingness to participate in study.
Exclusion Criteria:
-
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 1000per microliters (1000/μL) [1.0 x 10^9/L]), or human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS).
-
Has known selective Immunoglobulin A (IgA) deficiency (with or without antibodies to IgA).
-
Has isolated IgG subclass deficiency or an isolated specific antibody deficiency disorder, or transient hypogammaglobulinemia of infancy
-
The subject has had a known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction to blood or any blood-derived product.
-
Has a history of thrombotic complications following IVIG therapy.
-
Has a history of or current diagnosis of deep venous thrombosis (DVT) or thromboembolism (example, myocardial infarction, cerebrovascular accident or transient ischemic attack).
-
Has a known hyperviscosity syndrome or hypercoagulable states.
-
Has liver enzyme levels (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gammaglutamyl transferase [GGT], or lactate dehydrogenase [LDH]) greater than 2.5 times the upper limit of normal (ULN) at the screening visit as defined by the testing laboratory.
-
Has pre-existing renal impairment (defined by serum creatinine greater than 1.5 times the ULN or blood urea nitrogen [BUN] greater than 2.5 times the ULN, or any subject who is on dialysis) at the screening visit or any history of acute renal injury.
-
Has clinically significant history of drug or alcohol abuse or dependence in the opinion of the Investigator (must be within the past 12 months and noted in the subject's medical records or documented at screening).
-
Clinical evidence of any significant acute or chronic medical condition (example, renal disease or predisposing conditions for renal disease, coronary artery disease, or protein losing state) that, in the opinion of the Investigator, may interfere with the conduct of the study or may place the subject at undue medical risk.
-
Females of childbearing potential who are pregnant, have a positive pregnancy test at Screening (human chorionic gonadotropin [HCG]-based assay), are breastfeeding, or unwilling to practice a highly effective method of contraception (eg, oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device [IUD] or intrauterine system [IUS], condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study
-
Receiving any of the following medications: (a) immunosuppressants including chemotherapeutic agents, (b) immunomodulators, (c) long-term systemic corticosteroids defined as daily dose >1 mg of prednisone equivalent/kg/day for >30 days
-
Has uncontrolled arterial hypertension (systolic blood pressure [SBP] >160 mm Hg and/or diastolic blood pressure [DBP] >100 mm Hg)
-
Has hemoglobin <11 g/dL at the Screening Visit
-
Unable or unwilling to provide a storage serum sample at the Screening Visit
-
Received any live virus vaccine within 5 months prior to the Screening Visit and not willing to postpone receiving any live virus vaccines until 6 months after completing study treatment
-
Has a known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
-
Has participated in another clinical trial within 30 days prior to Screening or has received any investigational product, with the exception of other IgG products, within the previous 3 months prior to the Screening Visit
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Alabama Allergy & Asthma Center | Birmingham | Alabama | United States | 35209 |
| 2 | Allergy Associates of the Palm Beaches PA | North Palm Beach | Florida | United States | 33408 |
| 3 | The South Bend Clinic Center for Research | South Bend | Indiana | United States | 56617 |
| 4 | Institute for Asthma and Allergy | Chevy Chase | Maryland | United States | 20815 |
| 5 | Washington University | Saint Louis | Missouri | United States | 63141 |
| 6 | Optimed Research, LLC | Columbus | Ohio | United States | 43235 |
| 7 | OIAA Clinical Research, LLC | Oklahoma City | Oklahoma | United States | 73131 |
| 8 | Allergy, Asthma and Immunology Center, P.C. | Tulsa | Oklahoma | United States | 74136 |
| 9 | Allergy Partners of North Texas Research | Dallas | Texas | United States | 75230 |
| 10 | AARA Research Center | Dallas | Texas | United States | 75231 |
| 11 | Allergy, Asthma & Immunology Clinic, P.A. | Irving | Texas | United States | 75063 |
Sponsors and Collaborators
- Grifols Therapeutics LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GC1902