Study to Evaluate Safety and Pharmacokinetics of BIVIGAM® in Primary Immune Deficiency Subjects Aged 2 to 16

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

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.

Study Overview

• Status: Completed
• Conditions: Humoral Immune Response
• Intervention / Treatment: Biological: Bivigam

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe Research Centers
  • Florida
    • Durham, Florida, United States, 27710
      • Duke University Medical Center
    • North Palm Beach, Florida, United States, 33408
      • Allergy Associates of the Palm Beaches
    • Saint Petersburg, Florida, United States, 33701
      • USF Health, Pediatric Allergy, Immunology & Rheumatology
  • Ohio
    • Mayfield Heights, Ohio, United States, 44124
      • Ohio Clinical Research Associates
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73131
      • Oklahoma Institute of Allergy and Asthma Clinical Research
  • Texas
    • Dallas, Texas, United States, 75225
      • Discovery Clinical Trials
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Lysosomal Rare Disorders Research & Treatment Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 16 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Active Drug; All subjects will receive Bivigam based on their prior dosing to be adjusted as clinically necessary.	Biological: Bivigam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporally Associated Adverse Events	Incidence of adverse events (During or within 1 hour, 24 hours and 72 hours of completion of an infusion)	During each infusion (During or within 1 hour, 24 hours and 72 hours of completion of an infusion)
Number of Temporally Associated Adverse Events	Mean number of temporally associated per infusion	Up to 72 hours of completion of an infusion
Serious Adverse Events	Incidence of serious adverse events	Up to approximately 7 months
Related Serious Adverse Events	Incidence of related serious adverse events	Up to approximately 7 months
Treatment Emergent Adverse Events	Incidence of treatment emergent adverse events	Up to approximately 7 months
Related Treatment Emergent Averse Events	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	Within 72 hours of infusion
Non-treatment Emergent Adverse Events	Incidence of adverse events which do not have a causal relationship with study treatment	Up to approximately 7 months
Temporally Associated Infusion Adverse Events	Incidence of adverse events which have a causal relationship with infusion treatment	Up to approximately 7 months
Adverse Reactions	Number and incidence of adverse reactions plus suspected adverse reactions combined	Up to approximately 7 months
Related Adverse Reactions	Incidence of adverse infusion related reactions	Up to approximately 7 months
Infusion Site Reactions	Incidence reactions occuring at the infusion site	Up to approximately 7 months
Vital Signs	Change in vital signs	Before and after each administration of study drug through study completion, up to approximately 7 months
Temporally Associated Adverse Events Following Infusions	Incidence of adverse events	Up to 72 hours after each infusion through study completion, up tp approximately 7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total IgG Trough	Levels taken before any infusion	At each visit through study completion, up tp approximately 7 months
IgG subclasses	Levels of subclasses 1- 4 before infusion	Prior to first and last infusion, up tp approximately 7 months
Total IgG Post	End of infusion level of Total IgG	At each infusion through study completion, up tp approximately 7 months
Cmax	Pharmacokinetic measure at 5th or 7th infusion	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
Tmax	Pharmacokinetic measure at 5th or 7th infusion	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
AUC(0-ʈ)	Pharmacokinetic measure at 5th or 7th infusion	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
AUC(0-∞)	Pharmacokinetic measure at 5th or 7th infusion	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
Terminal phase elimination half-life (ʈ½)	Pharmacokinetic measure at 5th or 7th infusion	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
Antibodies	Levels of specific antibodies (antipneumococcal capsular polysaccharide, antihaemophilus influenza B	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
Infections	Number of infections of any kind, serious and non-serious	Up to approximately 7 months
First Serious Bacterial Infection	Time to first Serious Bacterial Infections in days	Up to approximately 7 months
Serious Bacterial Infections	Incidence of Serious Bacterial Infections	Up to approximately 7 months
Other Infections	Incidence of infections other than Serious Bacterial Infections	Up to approximately 7 months
Resolution of Infections	Time to resolution of Infections in days	Up to approximately 7 months
Fever	Episodes of Fever	Up to approximately 7 months
Missed Days	Number of days missed of school or work due to infections and treatment	Up to approximately 7 months
Hospitalizations	Number of hospitalizations due to infections	Up to approximately 7 months
Terminal phase elimination rate (λZ)	Pharmacokinetic measure at 5th or 7th infusion	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

Collaborators and Investigators

• Sponsor: ADMA Biologics, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 29, 2016
• Primary Completion (ACTUAL): August 30, 2022
• Study Completion (ACTUAL): December 31, 2022

Study Registration Dates

• First Submitted: January 30, 2017
• First Submitted That Met QC Criteria: May 23, 2017
• First Posted (ACTUAL): May 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2023
• Last Update Submitted That Met QC Criteria: January 30, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulin G
• Other Study ID Numbers: 994

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Not yet determined

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No