Study to Evaluate Safety and Pharmacokinetics of BIVIGAM® in Primary Immune Deficiency Subjects Aged 2 to 16
- Conditions
- Humoral Immune Response
- Interventions
- Biological: Bivigam
- Registration Number
- NCT03164967
- Lead Sponsor
- ADMA Biologics, Inc.
- Brief Summary
This study is part of the BIVIGAM® post marketing requirement (PMR). It is being conducted in subjects aged 2-16 with primary immune deficiency disorders associated with defects in humoral immunity to generate additional data on these populations, and more specifically safety and pharmacokinetic (PK) assessments.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
- Written informed consent/Assent
- Male or female between 2 and 16 years, inclusive, at time of Signing Informed Consent/Assent
- Have a confirmed and documented clinical diagnosis of Primary Immune Deficiency Disorder, including hypogammaglobulinemia or agammaglobulinemia.
- Have received IGIV therapy which was maintained at a steady dose (± 25% of the mean dose) for at least 3 months prior to study entry, and have maintained a trough IgG level at least 500mg/dL prior to receiving BIVIGAM®.
- Subjects and/or parents/legal guardians must be able to understand and adhere to the study visit schedule and all other protocol requirements.
- Known intolerance to immunoglobulins or comparable substances (e.g. vaccination reaction).
- Known intolerance to proteins of human origin or known allergic reactions to components of the study product(s).
- Any previous randomization/participation in this clinical study must be discussed with and approved by the medical director (or designee).
- Inability or lacking motivation to participate in the study.
- Medical condition, laboratory finding, or physical exam finding (specify, e.g., vital signs outside of specific range that precludes participation. Per lab results at the Screening visit through Baseline.
- Confirmed Screening visit laboratory results ˃2.5 X ULN as defined for pediatric populations for any of the following: ALT (alanine aminotransferase/SGPT), AST (aspartate aminotransferase/SGOT), LDH (lactate dehydrogenase), BUN (blood urea nitrogen), Serum creatinine
- Has selective IgA deficiency or demonstrated antibodies to IgA.
- History of thrombotic complications of IGIV therapy or history of (deep vein thrombosis)DVT.
- Current use of daily corticosteroids (>10 mg of prednisone equivalent/day),immunosuppressants or immunomodulators are not allowed unless approved in advance by the medical monitor. Intermittent use of corticosteroids during the study is allowed if medically necessary.
- Positive diagnosis of hepatitis B or hepatitis C.
- Positive human immunodeficiency virus (HIV) test.
- Subject has had a serious bacterial infection (SBI) within the last 3 months.
- Subject has an active infection and is receiving antibiotic therapy for the treatment of this infection at the time of Screening. Note: if the subject is deemed a Screen Failure due to a nonserious active infection requiring antibiotic therapy, the subject may be rescreened 3 or 4 weeks (depending on drug administration schedule) after the initial screening.
- Subject has a history of thrombotic events (including deep vein thrombosis, myocardial infarction, cerebrovascular accident and pulmonary embolism) within 6 months before 1st IGIV dose or has preexisting risk factors for thrombotic events.
- Acquired medical condition known to cause secondary immune deficiency such as chronic lymphacitic leukemia, lymphoma or multiple lymphoma.
- Subjects with protein-losing enteropathies, hypoalbuminaemia.
- Females taking oral contraceptives.
- Pregnancy or unreliable contraceptive measures or lactation period (females of childbearing potential (female capable of becoming pregnant) only. Males capable of reproduction must agree to a double barrier method of contraception during their study participation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Active Drug Bivigam All subjects will receive Bivigam based on their prior dosing to be adjusted as clinically necessary.
- Primary Outcome Measures
Name Time Method Infusion Site Reactions Up to approximately 7 months Incidence reactions occuring at the infusion site
Serious Adverse Events Up to approximately 7 months Incidence of serious adverse events
Temporally Associated Adverse Events During each infusion (During or within 1 hour, 24 hours and 72 hours of completion of an infusion) Incidence of adverse events (During or within 1 hour, 24 hours and 72 hours of completion of an infusion)
Related Serious Adverse Events Up to approximately 7 months Incidence of related serious adverse events
Treatment Emergent Adverse Events Up to approximately 7 months Incidence of treatment emergent adverse events
Temporally Associated Infusion Adverse Events Up to approximately 7 months Incidence of adverse events which have a causal relationship with infusion treatment
Non-treatment Emergent Adverse Events Up to approximately 7 months Incidence of adverse events which do not have a causal relationship with study treatment
Adverse Reactions Up to approximately 7 months Number and incidence of adverse reactions plus suspected adverse reactions combined
Related Adverse Reactions Up to approximately 7 months Incidence of adverse infusion related reactions
Temporally Associated Adverse Events Following Infusions Up to 72 hours after each infusion through study completion, up tp approximately 7 months Incidence of adverse events
Number of Temporally Associated Adverse Events Up to 72 hours of completion of an infusion Mean number of temporally associated per infusion
Related Treatment Emergent Averse Events Within 72 hours of infusion Incidence of adverse events that first appear, or that worsen relative to the pre-treatment state, which occur during and within 72 hours of treatment administration
Vital Signs Before and after each administration of study drug through study completion, up to approximately 7 months Change in vital signs
- Secondary Outcome Measures
Name Time Method Serious Bacterial Infections Up to approximately 7 months Incidence of Serious Bacterial Infections
IgG subclasses Prior to first and last infusion, up tp approximately 7 months Levels of subclasses 1- 4 before infusion
Cmax At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months Pharmacokinetic measure at 5th or 7th infusion
Other Infections Up to approximately 7 months Incidence of infections other than Serious Bacterial Infections
Resolution of Infections Up to approximately 7 months Time to resolution of Infections in days
Missed Days Up to approximately 7 months Number of days missed of school or work due to infections and treatment
Hospitalizations Up to approximately 7 months Number of hospitalizations due to infections
Total IgG Trough At each visit through study completion, up tp approximately 7 months Levels taken before any infusion
Fever Up to approximately 7 months Episodes of Fever
Tmax At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months Pharmacokinetic measure at 5th or 7th infusion
AUC(0-∞) At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after infusion Pharmacokinetic measure at 5th or 7th infusion
Infections Up to approximately 7 months Number of infections of any kind, serious and non-serious
Total IgG Post At each infusion through study completion, up tp approximately 7 months End of infusion level of Total IgG
AUC(0-ʈ) At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months Pharmacokinetic measure at 5th or 7th infusion
Terminal phase elimination half-life (ʈ½) At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months Pharmacokinetic measure at 5th or 7th infusion
Antibodies At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months Levels of specific antibodies (antipneumococcal capsular polysaccharide, antihaemophilus influenza B
First Serious Bacterial Infection Up to approximately 7 months Time to first Serious Bacterial Infections in days
Terminal phase elimination rate (λZ) At prior to, at end of infusion, and 6 hours, 24 hours, 7 days, and 4 days, 21 days and 28 days (if still enrolled) after final infusion, up tp approximately 7 months Pharmacokinetic measure at 5th or 7th infusion
Trial Locations
- Locations (8)
IMMUNOe Research Centers
🇺🇸Centennial, Colorado, United States
Ohio Clinical Research Associates
🇺🇸Mayfield Heights, Ohio, United States
Allergy Associates of the Palm Beaches
🇺🇸North Palm Beach, Florida, United States
USF Health, Pediatric Allergy, Immunology & Rheumatology
🇺🇸Saint Petersburg, Florida, United States
Duke University Medical Center
🇺🇸Durham, Florida, United States
Oklahoma Institute of Allergy and Asthma Clinical Research
🇺🇸Oklahoma City, Oklahoma, United States
Discovery Clinical Trials
🇺🇸Dallas, Texas, United States
Lysosomal Rare Disorders Research & Treatment Center
🇺🇸Fairfax, Virginia, United States