Safety and Pharmacokinetics of IGSC 20% in Subjects With Primary Immunodeficiency
- Conditions
- Primary Immunodeficiency
- Interventions
- Biological: IGIV-C 10%Biological: IGSC 20%
- Registration Number
- NCT02604810
- Lead Sponsor
- Grifols Therapeutics LLC
- Brief Summary
This study was designed to determine a dose of weekly subcutaneously administered Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (Grifols) (IGSC 20%) that produces steady-state AUC of total IgG that was non-inferior to that of the regularly administered intravenous dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified (Grifols) (IGIV-C 10%) in primary immunodeficiency subjects. This study was also designed to determine steady state trough total IgG levels after IGSC 20% infusion and after IGIV-C 10% infusion for comparison and to assess the safety and tolerability of IGSC 20%.
- Detailed Description
This was a prospective, multi-center, open-label, single-sequence, 6-month, pharmacokinetic, safety and tolerability study of IGSC 20% in subjects with primary immunodeficiency. Approximately 50 subjects were to be enrolled in order to have approximately 30 adult subjects and 12 to 18 pediatric subjects (age 2-16 years) completing treatment with subcutaneously administered IGSC 20%.
This study included 3 treatment phases: Run-In Phase, IV Phase (IV administration of IGIV-C 10% treatment), and SC Phase (SC administration of IGSC 20%).
Subjects, depending on their current IgG treatment regimen, might be required to enter the Run-In Phase to receive IV IGIV-C 10% treatment (Sponsor provided) to achieve an approximately steady-state condition prior to entering the IV Phase. They then entered the IV Phase to determine the AUC profiles of IV infusions of IGIV-C 10%.
Subjects with a qualifying IV IGIV-C 10% treatment regimen (on stable IGIV-C 10% doses of 300-800 mg/kg) entered the IV Phase directly where they will receive IGIV-C 10%. In the IV Phase, steady-state IV PK assessments, including AUC, were to be performed.
After completing the IV Phase, subjects entered the SC Phase to receive weekly SC doses of IGSC 20% for at least 24 weeks.
The PK profiles of total IgG following administration of both IV (IGIV-C 10%) administration and SC (IGSC 20%) administration were determined and compared after reaching approximate steady-state conditions.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 53
- Pre-existing diagnosis of primary immunodeficiency with features of hypogammaglobulinemia requiring IgG replacement therapy
- No serious bacterial infection within the last 3 months prior to or during Screening
- Currently on IgG replacement therapy (via IV or SC infusion) for ≥3 consecutive months. Subjects receiving IGIV must be receiving a dosage of 300 to 800 mg/kg per infusion
- Documented (at least once within previous 3 months) IgG trough level of ≥500 mg/dL on current IgG replacement therapy regimen
- Known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction to blood or any blood-derived product
- History of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections, or other disorders where SC therapy would be contraindicated during the study
- Isolated IgG subclass deficiency, isolated specific antibody deficiency disorder, or transient hypogammaglobulinemia of infancy
- Nephrotic syndrome, and/or a history of acute renal failure and/or severe renal impairment, and/or on dialysis
- History (year prior to Screening or 2 episodes in lifetime ) of or current diagnosis of deep venous thrombosis or thromboembolism (eg, deep vein thrombosis, myocardial infarction, cerebrovascular accident or transient ischemic attack)
- Acquired medical condition known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (absolute neutrophil count less than 1000/μL [1.0 x 10^9/L]), or human immunodeficiency virus infection/acquired immune deficiency syndrome
- Known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus or hepatitis C virus infection
- Non-controlled arterial hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg in adult subjects)
- 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 Note: Intermittent courses of corticosteroids of not more than 10 days would not exclude a subject. Inhaled or topical corticosteroids are allowed.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description IGIV-C 10% IGIV-C 10% IV dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified (Grifols) IGSC 20% IGSC 20% Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (Grifols)
- Primary Outcome Measures
Name Time Method AUC in the IV Phase and SC Phases: Steady-state AUC of Total IgG Over a Regular Dosing Interval For intravenous infusion, predose, 0,1,3-16 hours and 1,2,3,5,7,14,21 or 28 days (2, 7, 21, or 28 days for pediatric subjects) post-dose and for subcutaneous infusion, pre-dose,1,3,4,5,7 days (3 and 7 days for pediatric subjects) post-dose The primary PK endpoint (steady-state AUC values) analysis was performed using analysis of variance (ANOVA) using PK data from a total of 49 subjects from the IV phase and 39 subjects from the SC phase.
- Secondary Outcome Measures
Name Time Method Mean Steady-state Trough (Pre-dose) Concentration of Total IgG Following IV Administration of IGIV-C 10% or SC Administration of IGSC 20% For intravenous infusion, pre-dose at Week 1 and Week 3 or Week 4 and for subcutaneous infusion, predose at Weeks 13, 14, 17, and 21
Trial Locations
- Locations (25)
Allergy Associates of The Palm Beaches, PA
🇺🇸North Palm Beach, Florida, United States
University of South Florida
🇺🇸Saint Petersburg, Florida, United States
CHU Sainte-Justine
🇨🇦Montreal, Quebec, Canada
The Hospital for Sick Children
🇨🇦Toronto, Canada
AARA Research Center
🇺🇸Dallas, Texas, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
McGill University Health Center
🇨🇦Montreal, Canada
University of Miami - Batchelor Children's Research Institute
🇺🇸Miami, Florida, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Midwest Immunology
🇺🇸Plymouth, Minnesota, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
AIRE Medical of Los Angeles
🇺🇸Santa Monica, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Emory Children's Center
🇺🇸Atlanta, Georgia, United States
The South Bend Clinic
🇺🇸South Bend, Indiana, United States
Children's Hospital of Michigan - Wayne State University
🇺🇸Detroit, Michigan, United States
Washington University Medical Center
🇺🇸Saint Louis, Missouri, United States
Vital Prospects Clinical Research Institute, PC
🇺🇸Tulsa, Oklahoma, United States
Oklahoma Institute of Allergy and Asthma Clinical Research
🇺🇸Oklahoma City, Oklahoma, United States
Baylor Texas Children's Hospital
🇺🇸Houston, Texas, United States
Penn State University
🇺🇸Hershey, Pennsylvania, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Children's Hospital of Richmond at VCU, VCU Medical Center
🇺🇸Richmond, Virginia, United States
Ottawa Hospital, Division of Infectious Disease and Respirology
🇨🇦Ottawa, Ontario, Canada
Clinique d'asthme et d'allergie de Quebec
🇨🇦Quebec, Canada