Clinical trial NCT03164967: Study to Evaluate Safety and Pharmacokinetics of BIVIGAM® in Primary Immune Deficiency Subjects Aged 2 to 16
Official title: A Phase IV, Multicenter, Open-label Study to Evaluate the Safety and Pharmacokinetics of BIVIGAM® in Primary Immune Deficiency Disorders in Subjects Aged 2 to 16
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Humoral Immune Response
Lead sponsor: ADMA Biologics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-05-24
Enrollment: 16
Sex: ALL
Minimum age (years): 2
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Temporally Associated Adverse Events
timeFrame: During each infusion (During or within 1 hour, 24 hours and 72 hours of completion of an infusion)
measure: Number of Temporally Associated Adverse Events
timeFrame: Up to 72 hours of completion of an infusion
measure: Serious Adverse Events
timeFrame: Up to approximately 7 months
measure: Related Serious Adverse Events
timeFrame: Up to approximately 7 months
measure: Treatment Emergent Adverse Events
timeFrame: Up to approximately 7 months
measure: Related Treatment Emergent Averse Events
timeFrame: Within 72 hours of infusion
measure: Non-treatment Emergent Adverse Events
timeFrame: Up to approximately 7 months
measure: Temporally Associated Infusion Adverse Events
timeFrame: Up to approximately 7 months
measure: Adverse Reactions
timeFrame: Up to approximately 7 months
measure: Related Adverse Reactions
timeFrame: Up to approximately 7 months
measure: Infusion Site Reactions
timeFrame: Up to approximately 7 months
measure: Vital Signs
timeFrame: Before and after each administration of study drug through study completion, up to approximately 7 months
measure: Temporally Associated Adverse Events Following Infusions
timeFrame: Up to 72 hours after each infusion through study completion, up tp approximately 7 months
Secondary outcomes:
measure: Total IgG Trough
timeFrame: At each visit through study completion, up tp approximately 7 months
measure: IgG subclasses
timeFrame: Prior to first and last infusion, up tp approximately 7 months
measure: Total IgG Post
timeFrame: At each infusion through study completion, up tp approximately 7 months
measure: Cmax
timeFrame: 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
measure: Tmax
timeFrame: 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
measure: AUC(0-ʈ)
timeFrame: 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
measure: AUC(0-∞)
timeFrame: 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
measure: Terminal phase elimination half-life (ʈ½)
timeFrame: 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
measure: Antibodies
timeFrame: 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
measure: Infections
timeFrame: Up to approximately 7 months
measure: First Serious Bacterial Infection
timeFrame: Up to approximately 7 months
measure: Serious Bacterial Infections
timeFrame: Up to approximately 7 months
measure: Other Infections
timeFrame: Up to approximately 7 months
measure: Resolution of Infections
timeFrame: Up to approximately 7 months
measure: Fever
timeFrame: Up to approximately 7 months
measure: Missed Days
timeFrame: Up to approximately 7 months
measure: Hospitalizations
timeFrame: Up to approximately 7 months
measure: Terminal phase elimination rate (λZ)
timeFrame: 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
Other outcomes:
Locations:
city: Centennial
country: United States
facility: IMMUNOe Research Centers
state: Colorado
city: Durham
country: United States
facility: Duke University Medical Center
state: Florida
city: North Palm Beach
country: United States
facility: Allergy Associates of the Palm Beaches
state: Florida
city: Saint Petersburg
country: United States
facility: USF Health, Pediatric Allergy, Immunology & Rheumatology
state: Florida
city: Mayfield Heights
country: United States
facility: Ohio Clinical Research Associates
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Institute of Allergy and Asthma Clinical Research
state: Oklahoma
city: Dallas
country: United States
facility: Discovery Clinical Trials
state: Texas
city: Fairfax
country: United States
facility: Lysosomal Rare Disorders Research & Treatment Center
state: Virginia
Study officials:
References: