Clinical trial NCT01465958: Pharmacokinetics, Safety, and Tolerability of Subcutaneous GAMUNEX-C in Pediatric Subjects With Primary Immunodeficiency
Official title: An Open-label, Single-sequence, Crossover Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Subcutaneous GAMUNEX®-C in Pediatric Subjects With Primary Immunodeficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Primary Immunodeficiency
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2011-11-06
Enrollment: 12
Sex: ALL
Minimum age (years): 2
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this open-label study is to evaluate the pharmacokinetics, safety, and tolerability of subcutaneously (SC; under the skin) administered GAMUNEX-C compared to intravenously (IV; through the vein) administered GAMUNEX-C in subjects 2-16 years of age with Primary Immunodeficiency.

Detailed description: This study was a multi-center, open-label, single-sequence, crossover study to evaluate the pharmacokinetics (PK), safety and tolerability of SC-administered GAMUNEX-C in pediatric PI subjects (ages 2-16). The study consisted of a Screening Phase, Run-in Phase, two treatment phases (an IV Phase and a SC Phase), and an End of Study/Early Termination (EOS/ET) visit. Run-in phase: 3 - 4 months, IV Phase: \~ 4 - 5 weeks, SC Phase: 12 weeks, and End of Study/Early Termination (EOS/ET) visit: one week after SC Week #12.

Eligibility criteria: Inclusion Criteria:

* Aged 2-16 years old, inclusive.
* Documented and confirmed pre-existing diagnosis of PI with features of hypogammaglobulinemia requiring immunoglobulin replacement.
* Currently on IgG replacement therapy with a serum IgG trough concentration of ≥ 500 mg/dL at the Screening Visit.
* Adequate normal skin to allow for SC infusions.
* Signs an assent form, if applicable (per Institutional Review Board \[IRB\] requirements). Parent or legal guardian must sign an informed consent form.
* Females of childbearing potential must have a negative urine pregnancy test result and must practice an effective form of contraception (which may include abstinence).

Exclusion Criteria:

* History of anaphylaxis or severe systemic response to an immunoglobulin or blood product.
* History of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, recurrent skin infections or other disorders where subcutaneous therapy could be contraindicated.
* Has a specific antibody deficiency disorder, IgG subclass deficiency, or transient hypogammaglobulinemia of infancy.
* History of severe adverse reaction to parenteral products containing immunoglobulin A (IgA).
* Significant proteinuria and/or has a history of acute renal failure and/or severe renal impairment (serum creatinine more than 2.5 times the upper limit of normal \[ULN\] for age and gender) and/or is on dialysis.
* Known substance or prescription drug abuse in the past 12 months.
* Acquired medical condition that is known to cause secondary immune deficiency.
* Receiving any of the following medications: systemic corticosteroids (long term daily, \>1 mg of prednisone equivalent/kg/day for \>30 days) (intermittent courses would not exclude subject); immunosuppressants (i.e., antimetabolites and systemic calcineurin inhibitors; NOTE: inhaled steroids are allowed); or immunomodulators.
* Non-controlled arterial hypertension at a level of ≥ the 90th percentile blood pressure (either systolic or diastolic) for age and height (based on http://www.nhlbi.nih.gov/guidelines/hypertension/child_tbl.pdf ).
* History or current diagnosis of thrombotic episodes; venous thrombus that occurred in association with a medical device \> 2 years prior to screening are allowed.
* Currently receiving anti-coagulation therapy.
* History of Kawasaki disease.
* Participated in another clinical trial involving exposure to an investigational product or device 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.
* Unable or unwilling to comply with any aspect of the protocol, including blood sampling and completion of the Infusion Site Reactions pages in the SC Infusion Diary.
* In the opinion of the Investigator the subject may have compliance problems with the protocol and the procedures of the protocol.
* Pregnant or lactating.
* Clinical evidence of any significant acute or chronic disease that, in the opinion of the Investigator, may interfere with successful completion of the study.

Primary outcomes:
measure: Steady-state Area Under the Curve (AUC) for Serum Total Immunoglobulin (IgG)
timeFrame: 4 to 5 weeks for IV administration; 12 weeks for SC administration
measure: Mean Trough of Serum Total IgG
timeFrame: 4 - 5 weeks of IV administration and 12 weeks for SC administration
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Centennial
country: United States
facility: IMMUNOe International Research Centers
state: Colorado
city: Hollywood
country: United States
facility: Joe DiMaggio Children's Hospital
state: Florida
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
References:
citation: Heimall J, Chen J, Church JA, Griffin R, Melamed I, Kleiner GI. Pharmacokinetics, Safety, and Tolerability of Subcutaneous Immune Globulin Injection (Human), 10 % Caprylate/Chromatography Purified (GAMUNEX(R)-C) in Pediatric Patients with Primary Immunodeficiency Disease. J Clin Immunol. 2016 Aug;36(6):600-9. doi: 10.1007/s10875-016-0311-4. Epub 2016 Jun 25.