Humoral Immune ResponsePhase 4NCT03164967
Study to Evaluate Safety and Pharmacokinetics of BIVIGAM® in Primary Immune Deficiency Subjects Aged 2 to 16
A Phase 4 study testing Bivigam in people with Humoral Immune Response, run by ADMA Biologics, Inc. at 8 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 2 to 16 years
- Conditions the study is for
- Humoral Immune Response
- What is being tested?
- Bivigam
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 8 sitesUnited States
- Study dates
- 29 Dec 2016to 31 Dec 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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
Show all 18Show fewer
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
IMMUNOe Research Centers
Centennial, Colorado, 80112
Discovery Clinical Trials
Dallas, Texas, 75225
Duke University Medical Center
Durham, Florida, 27710
Lysosomal Rare Disorders Research & Treatment Center
Fairfax, Virginia, 22030
Ohio Clinical Research Associates
Mayfield Heights, Ohio, 44124
Allergy Associates of the Palm Beaches
North Palm Beach, Florida, 33408
Oklahoma Institute of Allergy and Asthma Clinical Research
Oklahoma City, Oklahoma, 73131
USF Health, Pediatric Allergy, Immunology & Rheumatology
St. Petersburg, Florida, 33701
About this study
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
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.
- Conditions
- Humoral Immune Response
- Being tested
- Bivigam
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BivigamBiological
| Study group | Role | What they receive |
|---|---|---|
| Active Drug | Other | All subjects will receive Bivigam based on their prior dosing to be adjusted as clinically necessary. Receives: Biological: Bivigam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Temporally Associated Adverse Events
Incidence of adverse events (During or within 1 hour, 24 hours and 72 hours of completion of an infusion)
Measured: 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
Measured: Up to 72 hours of completion of an infusion
Serious Adverse Events
Incidence of serious adverse events
Measured: Up to approximately 7 months
Related Serious Adverse Events
Incidence of related serious adverse events
Measured: Up to approximately 7 months
Treatment Emergent Adverse Events
Incidence of treatment emergent adverse events
Measured: 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
Measured: Within 72 hours of infusion
Non-treatment Emergent Adverse Events
Incidence of adverse events which do not have a causal relationship with study treatment
Measured: Up to approximately 7 months
Temporally Associated Infusion Adverse Events
Incidence of adverse events which have a causal relationship with infusion treatment
Measured: Up to approximately 7 months
Adverse Reactions
Number and incidence of adverse reactions plus suspected adverse reactions combined
Measured: Up to approximately 7 months
Related Adverse Reactions
Incidence of adverse infusion related reactions
Measured: Up to approximately 7 months
Infusion Site Reactions
Incidence reactions occuring at the infusion site
Measured: Up to approximately 7 months
Vital Signs
Change in vital signs
Measured: 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
Measured: Up to 72 hours after each infusion through study completion, up tp approximately 7 months
Secondary outcomes (18)
Total IgG Trough
Levels taken before any infusion
Measured: At each visit through study completion, up tp approximately 7 months
IgG subclasses
Levels of subclasses 1- 4 before infusion
Measured: Prior to first and last infusion, up tp approximately 7 months
Total IgG Post
End of infusion level of Total IgG
Measured: At each infusion through study completion, up tp approximately 7 months
Cmax
Pharmacokinetic measure at 5th or 7th infusion
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Up to approximately 7 months
First Serious Bacterial Infection
Time to first Serious Bacterial Infections in days
Measured: Up to approximately 7 months
Serious Bacterial Infections
Incidence of Serious Bacterial Infections
Measured: Up to approximately 7 months
Other Infections
Incidence of infections other than Serious Bacterial Infections
Measured: Up to approximately 7 months
Resolution of Infections
Time to resolution of Infections in days
Measured: Up to approximately 7 months
Fever
Episodes of Fever
Measured: Up to approximately 7 months
Missed Days
Number of days missed of school or work due to infections and treatment
Measured: Up to approximately 7 months
Hospitalizations
Number of hospitalizations due to infections
Measured: Up to approximately 7 months
Terminal phase elimination rate (λZ)
Pharmacokinetic measure at 5th or 7th infusion
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2017
- Study start29 Dec 2016
- Primary completion30 Aug 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Humoral Immune ResponseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- ADMA Biologics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03164967
- Sponsor's protocol ID
- 994
- Status last verified
- Jan 2023
- First submitted
- 30 Jan 2017
- Last updated
- 1 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Not yet determined
Publications
Dumas T, Mehr S, Avila R, Doman A, Kestenberg K, Melamed I. Pharmacokinetic Model Based Sensitivity Analysis to Lower Recruitment Burden for Young Children Requiring Intravenous Immunoglobulin G Replacement. CPT Pharmacometrics Syst Pharmacol. 2026 Jun;15(6):e70275. doi: 10.1002/psp4.70275.
PubMed 42218742
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03164967
- Acronym / sponsor ID
- 994
- Conditions
- Humoral Immune Response
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- ADMA Biologics, Inc.Industry (pharma, biotech, devices)
- Study start
- 29 Dec 2016 (actual)
- Primary completion
- 30 Aug 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 24 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active Drug | Other | Biological: BivigamAll subjects will receive Bivigam based on their prior dosing to be adjusted as clinically necessary. |
Who may qualify
- Ages
- 2 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bivigam | Biological | Active Drug |
Primary outcome
Temporally Associated Adverse Events
Time frame: 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
Time frame: Up to 72 hours of completion of an infusion
Mean number of temporally associated per infusion
Serious Adverse Events
Time frame: Up to approximately 7 months
Incidence of serious adverse events
Related Serious Adverse Events
Time frame: Up to approximately 7 months
Incidence of related serious adverse events
Treatment Emergent Adverse Events
Time frame: Up to approximately 7 months
Incidence of treatment emergent adverse events
Related Treatment Emergent Averse Events
Time frame: 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
Time frame: Up to approximately 7 months
Incidence of adverse events which do not have a causal relationship with study treatment
Temporally Associated Infusion Adverse Events
Time frame: Up to approximately 7 months
Incidence of adverse events which have a causal relationship with infusion treatment
Adverse Reactions
Time frame: Up to approximately 7 months
Number and incidence of adverse reactions plus suspected adverse reactions combined
Related Adverse Reactions
Time frame: Up to approximately 7 months
Incidence of adverse infusion related reactions
Infusion Site Reactions
Time frame: Up to approximately 7 months
Incidence reactions occuring at the infusion site
Vital Signs
Time frame: 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
Time frame: Up to 72 hours after each infusion through study completion, up tp approximately 7 months
Incidence of adverse events
18 secondary outcomes
Total IgG Trough
Time frame: At each visit through study completion, up tp approximately 7 months
IgG subclasses
Time frame: Prior to first and last infusion, up tp approximately 7 months
Total IgG Post
Time frame: At each infusion through study completion, up tp approximately 7 months
Cmax
Time frame: 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
Time frame: 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)
Time frame: 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-∞)
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: Up to approximately 7 months
First Serious Bacterial Infection
Time frame: Up to approximately 7 months
Serious Bacterial Infections
Time frame: Up to approximately 7 months
Other Infections
Time frame: Up to approximately 7 months
Resolution of Infections
Time frame: Up to approximately 7 months
Fever
Time frame: Up to approximately 7 months
Missed Days
Time frame: Up to approximately 7 months
Hospitalizations
Time frame: Up to approximately 7 months
Terminal phase elimination rate (λZ)
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2023.
- Derived from this study: PubMed 42218742Dumas T, Mehr S, Avila R, Doman A, Kestenberg K, Melamed I. Pharmacokinetic Model Based Sensitivity Analysis to Lower Recruitment Burden for Young Children Requiring Intravenous Immunoglobulin G Replacement. CPT Pharmacometrics Syst Pharmacol. 2026 Jun;15(6):e70275. doi: 10.1002/psp4.70275.
- Individual participant dataSharing planned: Undecided. Not yet determined
Related trials for Humoral Immune Response
Not yet recruitingObservational study
Characterization of Adaptive Immune Responses to Oropouche Virus (OROV) Infection
Oropouche Infection
RecruitingObservational study
Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Antiretroviral Naive HIV-1 Research Participants
HIV
Active, not recruitingPhase 2
Immunogenicity of the 9-Valent Human Papillomavirus Recombinant Vaccine in People With Idiopathic CD4 T Cell Lymphocytopenia
Idiopathic CD4 T Cell Lymphocytopenia
RecruitingObservational study
Immune Regulation in Patients With Common Variable Immunodeficiency and Related Inborn Errors of Immunity (IEI)
XLA, CVID
RecruitingObservational study
Send-In Sample Collection for Comprehensive Analyses of Innate and Adaptive Immune Responses During Acute COVID-19 and Convalescence
COVID-19 Infection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bivigam in people with Humoral Immune Response, run by ADMA Biologics, Inc. at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Temporally Associated Adverse Events (time frame: During each infusion (During or within 1 hour, 24 hours and 72 hours of completion of an infusion)). The study lists 13 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03164967, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2023.