Humoral Immune Response
Conditions
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.
Interventions
BIOLOGICALBivigam
Sponsors
ADMA Biologics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Number of Temporally Associated Adverse Events | Up to 72 hours of completion of an infusion | Mean number of temporally associated per infusion |
| Serious Adverse Events | Up to approximately 7 months | Incidence of serious adverse events |
| 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 |
| 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 |
| Non-treatment Emergent Adverse Events | Up to approximately 7 months | Incidence of adverse events which do not have a causal relationship with study treatment |
| Temporally Associated Infusion Adverse Events | Up to approximately 7 months | Incidence of adverse events which have a causal relationship with infusion 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 |
| Infusion Site Reactions | Up to approximately 7 months | Incidence reactions occuring at the infusion site |
| Vital Signs | Before and after each administration of study drug through study completion, up to approximately 7 months | Change in vital signs |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| First Serious Bacterial Infection | Up to approximately 7 months | Time to first Serious Bacterial Infections in days |
| Serious Bacterial Infections | Up to approximately 7 months | Incidence of Serious Bacterial Infections |
| Resolution of Infections | Up to approximately 7 months | Time to resolution of Infections in days |
| Hospitalizations | Up to approximately 7 months | Number of hospitalizations due to infections |
| 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 |
| Missed Days | Up to approximately 7 months | Number of days missed of school or work due to infections and treatment |
| Fever | Up to approximately 7 months | Episodes of Fever |
| Other Infections | Up to approximately 7 months | Incidence of infections other than Serious Bacterial Infections |
| Total IgG Trough | At each visit through study completion, up tp approximately 7 months | Levels taken before any infusion |
| IgG subclasses | Prior to first and last infusion, up tp approximately 7 months | Levels of subclasses 1- 4 before infusion |
| Total IgG Post | At each infusion through study completion, up tp approximately 7 months | End of infusion level of Total IgG |
| 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 |
| 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-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 |
| 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 |
| 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 |
| Infections | Up to approximately 7 months | Number of infections of any kind, serious and non-serious |
Countries
United States
Outcome results
None listed