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

Humoral Immune Response Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03164967
• Other study ID #: 994
• Status: Completed
• Phase: Phase 4
• Start date: December 29, 2016
• Est. completion date: December 31, 2022

Study information

• Verified date: January 2023
• Source: ADMA Biologics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 31, 2022
• Est. primary completion date: August 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 16 Years

Eligibility

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.

Related Conditions & MeSH terms

• Humoral Immune Response
• Immunologic Deficiency Syndromes
• Primary Immunodeficiency Diseases

Intervention

Biological:
• Bivigam

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
ADMA Biologics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Number of Temporally Associated Adverse Events	Mean number of temporally associated per infusion	Up to 72 hours of completion of an infusion
Primary	Serious Adverse Events	Incidence of serious adverse events	Up to approximately 7 months
Primary	Related Serious Adverse Events	Incidence of related serious adverse events	Up to approximately 7 months
Primary	Treatment Emergent Adverse Events	Incidence of treatment emergent adverse events	Up to approximately 7 months
Primary	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
Primary	Non-treatment Emergent Adverse Events	Incidence of adverse events which do not have a causal relationship with study treatment	Up to approximately 7 months
Primary	Temporally Associated Infusion Adverse Events	Incidence of adverse events which have a causal relationship with infusion treatment	Up to approximately 7 months
Primary	Adverse Reactions	Number and incidence of adverse reactions plus suspected adverse reactions combined	Up to approximately 7 months
Primary	Related Adverse Reactions	Incidence of adverse infusion related reactions	Up to approximately 7 months
Primary	Infusion Site Reactions	Incidence reactions occuring at the infusion site	Up to approximately 7 months
Primary	Vital Signs	Change in vital signs	Before and after each administration of study drug through study completion, up to approximately 7 months
Primary	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	Total IgG Trough	Levels taken before any infusion	At each visit through study completion, up tp approximately 7 months
Secondary	IgG subclasses	Levels of subclasses 1- 4 before infusion	Prior to first and last infusion, up tp approximately 7 months
Secondary	Total IgG Post	End of infusion level of Total IgG	At each infusion through study completion, up tp approximately 7 months
Secondary	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
Secondary	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
Secondary	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 final infusion, up tp approximately 7 months
Secondary	AUC(0-8)	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
Secondary	Terminal phase elimination half-life (?½)	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
Secondary	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
Secondary	Infections	Number of infections of any kind, serious and non-serious	Up to approximately 7 months
Secondary	First Serious Bacterial Infection	Time to first Serious Bacterial Infections in days	Up to approximately 7 months
Secondary	Serious Bacterial Infections	Incidence of Serious Bacterial Infections	Up to approximately 7 months
Secondary	Other Infections	Incidence of infections other than Serious Bacterial Infections	Up to approximately 7 months
Secondary	Resolution of Infections	Time to resolution of Infections in days	Up to approximately 7 months
Secondary	Fever	Episodes of Fever	Up to approximately 7 months
Secondary	Missed Days	Number of days missed of school or work due to infections and treatment	Up to approximately 7 months
Secondary	Hospitalizations	Number of hospitalizations due to infections	Up to approximately 7 months
Secondary	Terminal phase elimination rate (?Z)	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