Primary Immune Deficiency DisordersPhase 3GMX07NCT01963143
Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
A Phase 3 study testing Gammaplex (5%) and Gammaplex 10 in people with Primary Immune Deficiency Disorders and Common Variable Immunodeficiency, run by Bio Products Laboratory at 17 sites in 3 countries.
Trial summary
The primary objective is to demonstrate the bioequivalence of Gammaplex® 10 intravenous immunoglobulin (IGIV) and Gammaplex® 5% IGIV with respect to area under the curve within a 28-day dosing interval (AUC0-28) in a cohort of adult subjects. Read more about this study
- Who is it for?
- Ages 2 to 55 years
- Conditions the study is for
- Primary Immune Deficiency Disorders, Common Variable Immunodeficiency, X-linked Agammaglobulinaemia
- What is being tested?
- Gammaplex (5%) and Gammaplex 10
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 17 sitesin 3 countries
- Study dates
- Feb 2014to May 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Adult cohort: The subject is aged 16 to 55 years inclusive, is of either sex, and belongs to any ethnic group.
- Pediatric cohort: The subject is aged 2 to 15 years inclusive, is of either sex, weighs at least 10 kg, and belongs to any ethnic group.
- The subject has primary immunodeficiency disease, e.g. common variable immunodeficiency, X linked and autosomal forms of agammaglobulinemia, hyper IgM (Immunoglobulin M) syndrome. Isolated deficiency of a single IgG subclass or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion.
- The subject is currently receiving a licensed IGIV (or investigational stage III, IIIb IGIV) at a dose that has not changed by ± 50% of the mean dose for at least three months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be either every 21 or every 28 days.
- The subject must have a trough level ≥ 6 g/L (600 mg/dL). At least one documented trough level must be available from the three months before Screening.
- The subject must have documentation from the last three consecutive routine IGIV infusions for the following, before the first infusion in this study: dose of IGIV, treatment intervals, and trade name (or identity) of the IGIV treatment.
Show all 10Show fewer
- Female subjects of childbearing potential must have a negative result on an HCG (human chorionic gonadotropin) based pregnancy test at Screening.
- Females who are or become sexually active must practice contraception using a method of proven reliability for the study duration.
- The subject is willing to comply with all aspects of the protocol for the duration of the study.
- The subject has signed an informed consent form and assent form (if applicable).
Who cannot join
- The subject has a history of any severe anaphylactic reaction to blood or any blood derived product.
- The subject has selective IgA deficiency, history of reaction to products containing IgA (Immunoglobulin A), or has a history of antibodies to IgA.
- The subject has cellular or innate impaired immunity (i.e. only subjects with humoral impaired immunity may be included).
- The subject has evidence of an active infection at the time of enrolment.
- The subject has previously completed or withdrawn from this study.
- The subject is currently receiving, or has received, any investigational agent other than an IGIV within the prior three months.
Show all 27Show fewer
- The subject is pregnant or is nursing.
- The subject has positive results for any of the following at Screening:
- Serological test for HIV 1 and 2, HCV, or HBsAg
- NAT (Nucleic acid amplification technique)for HCV
- NAT for HIV
- The subject has levels > 2.5 times the upper limit of normal, as defined at the central laboratory, of any of the following at Screening:
- Alanine amino transaminase
- Aspartate amino transaminase
- The subject has severe renal impairment (defined as serum creatinine greater than two times the upper limit of normal or blood urea nitrogen greater than 2.5 times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; the subject has a history of acute renal failure.
- The subject is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.
- The subject has a history of deep vein thrombosis or thrombotic complications of IGIV therapy.
- The subject suffers from any acute or chronic* medical condition (e.g. renal disease or predisposing conditions for renal disease, coronary artery disease, or protein losing state) that the Investigator feels may interfere with the conduct of the study.
- The subject has an acquired immunodeficiency condition such as chronic* lymphocytic leukemia, lymphoma, multiple myeloma, or chronic or recurrent neutropenia (absolute neutrophil count < 1 × 109/L).
- The subject is receiving the following medication:
- Steroids (long term daily, ≥ 0.15 mg of prednisone equivalent/kg/day). Requirement for short or intermittent courses of steroids would not exclude a subject.
- Immunosuppressive drugs
- Immunomodulatory drugs
- The subject has uncontrolled arterial hypertension (systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg).
- The subject has anemia (hemoglobin < 10 g/dL) at Screening.
- The subject is known to be intolerant to any component of Gammaplex, such as sorbitol (i.e. hereditary intolerance to fructose) or glycine.
- Chronic conditions would be as per the Investigator's opinion however for this study the guidance is that the condition has been present for at least 6 months.
Trial locations and contacts
17 sites in 3 countries.
17 sites in 3 countries
United States14 sites
Bellingham Asthma Allergy and Immunology Clinic
Bellingham, Washington, 98225
IMMUNOe International Research Centers
Centennial, Colorado, 80112
Arizona Allergy Associates
Chandler, Arizona, 85224
Institute for Asthma and Allergy
Chevy Chase, Maryland, 20815
Rush University Medical Center
Chicago, Illinois, 60612
Dallas Allergy Immunology Research
Dallas, Texas, 75230
O&O Alpan, LLC
Fairfax, Virginia, 22030
Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Miller Children's Hospital
Long Beach, California, 90806
Childrens Hospital Los Angeles
Los Angeles, California, 90027
UCLA Medical Center
Los Angeles, California, 90095
Allergy Associates of the Palm Beaches, PA
North Palm Beach, Florida, 33408
University of Utah Primary Children's Hospital
Salt Lake City, Utah, 84113
Asthma and Allergy Center
Toledo, Ohio, 43617
United Kingdom2 sites
University Hospital of Wales
Cardiff, Wales, CF14 4XW
The Royal Free Hospital and Medical School
London, NW3 2QG
About this study
Official title: A Phase III, Multicenter, Open-label, Randomized, Two-Period, Crossover Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
The primary objective is to demonstrate the bioequivalence of Gammaplex® 10 intravenous immunoglobulin (IGIV) and Gammaplex® 5% IGIV with respect to area under the curve within a 28-day dosing interval (AUC0-28) in a cohort of adult subjects.
The secondary objectives are to demonstrate the bioequivalence of Gammaplex® 10 IGIV and Gammaplex® 5% IGIV with respect to area under the curve within a 21-day dosing interval (AUC0-21) in adult subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV and Gammaplex 5% IGIV including Immunoglobulin G (IgG) trough levels and to investigate the safety and tolerability of Gammaplex 10 IGIV and Gammaplex 5% IGIV in adults subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV including IgG trough levels and to investigate the safety and tolerability of Gammaplex 10 IGIV in pediatric subjects.
- Conditions
- Primary Immune Deficiency Disorders, Common Variable Immunodeficiency, X-linked Agammaglobulinaemia, Hyper-IgM Syndrome
- Being tested
- Gammaplex (5%), Gammaplex 10
- Medical subject headings
- Primary Immunodeficiency Diseases, Common Variable Immunodeficiency, Bruton type agammaglobulinemia, Hyper-IgM Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gammaplex (5%)Biological
Gammaplex 10Biological
| Study group | Role | What they receive |
|---|---|---|
| Treatment Sequence 1 - Adults | Experimental | Gammaplex 5% - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days, followed by Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days Receives: Biological: Gammaplex (5%); Biological: Gammaplex 10 |
| Treatment Sequence 2 - Adults | Experimental | Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days, followed by Gammaplex 5% - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days Receives: Biological: Gammaplex (5%); Biological: Gammaplex 10 |
| Pediatrics | Experimental | Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days Receives: Biological: Gammaplex 10 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Bioequivalence Analysis - Area Under the Curve Within a 28-day Dosing Interval (AUC0-28) in Adult Subjects
Measured: After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14, 21 and 28 days post-infusion
Secondary outcomes (2)
Secondary Bioequivalence Analysis - Area Under the Curve Within a 21-Day Dosing Interval (AUC0-21) in Adult Subjects
Measured: After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14 and 21 days post-infusion
Secondary Bioequivalence Analysis - IgG Trough Levels
Measured: After a minimum 5 infusions on each product, at pre-infusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2013 (estimated)
- Study startFeb 2014
- Primary completionJan 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Primary Immune Deficiency DisordersStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bio Products Laboratory
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Eric Wolford, Study director, Bio Products Laboratory
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01963143
- Sponsor's protocol ID
- GMX07
- Acronym
- GMX07
- Status last verified
- Feb 2017
- First submitted
- 13 Sep 2013
- Last updated
- 29 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Geng B, Clark K. Plain language summary: Headache and migraine experiences in people with primary immunodeficiency receiving GAMMAPLEX(R) 5% or 10% intravenous immunoglobulin therapy. Immunotherapy. 2026 Feb;18(2):65-74. doi: 10.1080/1750743X.2026.2633976. Epub 2026 Mar 3.
PubMed 41773292Rajendram V, Paddick M, More J. Measles neutralising antibody levels in patients receiving intravenous immunoglobulin treatment - a sub-analysis of a randomized, cross-over bioequivalence trial. PLoS One. 2025 Feb 7;20(2):e0316926. doi: 10.1371/journal.pone.0316926. eCollection 2025.
PubMed 39919133Paddick M, Clark K, Wolford E, More J. Protective antibody concentrations in primary immunodeficiency following infusion with 5% or 10% intravenous immunoglobulin. Allergy Asthma Proc. 2024 Nov 1;45(6):414-420. doi: 10.2500/aap.2024.45.240033. Epub 2024 Sep 13.
PubMed 39271296Geng B, Clark K, Evangelista M, Wolford E. Low rates of headache and migraine associated with intravenous immunoglobulin infusion using a 15-minute rate escalation protocol in 123 patients with primary immunodeficiency. Front Immunol. 2023 Feb 2;13:1075527. doi: 10.3389/fimmu.2022.1075527. eCollection 2022.
PubMed 36818468
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicenter, Open-label, Randomized, Two-Period, Crossover Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
- ClinicalTrials.gov ID
- NCT01963143
- Acronym / sponsor ID
- GMX07 / GMX07
- Conditions
- Primary Immune Deficiency Disorders, Common Variable Immunodeficiency, X-linked Agammaglobulinaemia, Hyper-IgM Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Bio Products LaboratoryUniversity, hospital or other
- Study start
- Feb 2014
- Primary completion
- Jan 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 16 Oct 2013 (estimated)
- Results
- Posted 29 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective is to demonstrate the bioequivalence of Gammaplex® 10 intravenous immunoglobulin (IGIV) and Gammaplex® 5% IGIV with respect to area under the curve within a 28-day dosing interval (AUC0-28) in a cohort of adult subjects.
The secondary objectives are to demonstrate the bioequivalence of Gammaplex® 10 IGIV and Gammaplex® 5% IGIV with respect to area under the curve within a 21-day dosing interval (AUC0-21) in adult subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV and Gammaplex 5% IGIV including Immunoglobulin G (IgG) trough levels and to investigate the safety and tolerability of Gammaplex 10 IGIV and Gammaplex 5% IGIV in adults subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV including IgG trough levels and to investigate the safety and tolerability of Gammaplex 10 IGIV in pediatric subjects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Treatment Sequence 1 - Adults | Experimental | Biological: Gammaplex (5%), Biological: Gammaplex 10Gammaplex 5% - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days, followed by Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days |
| Treatment Sequence 2 - Adults | Experimental | Biological: Gammaplex (5%), Biological: Gammaplex 10Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days, followed by Gammaplex 5% - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days |
| Pediatrics | Experimental | Biological: Gammaplex 10Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days |
Who may qualify
- Ages
- 2 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- Adult cohort: The subject is aged 16 to 55 years inclusive, is of either sex, and belongs to any ethnic group.
- Pediatric cohort: The subject is aged 2 to 15 years inclusive, is of either sex, weighs at least 10 kg, and belongs to any ethnic group.
- The subject has primary immunodeficiency disease, e.g. common variable immunodeficiency, X linked and autosomal forms of agammaglobulinemia, hyper IgM (Immunoglobulin M) syndrome. Isolated deficiency of a single IgG subclass or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion.
- The subject is currently receiving a licensed IGIV (or investigational stage III, IIIb IGIV) at a dose that has not changed by ± 50% of the mean dose for at least three months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be either every 21 or every 28 days.
- The subject must have a trough level ≥ 6 g/L (600 mg/dL). At least one documented trough level must be available from the three months before Screening.
Key exclusion criteria (27 listed)
- The subject has a history of any severe anaphylactic reaction to blood or any blood derived product.
- The subject has selective IgA deficiency, history of reaction to products containing IgA (Immunoglobulin A), or has a history of antibodies to IgA.
- The subject has cellular or innate impaired immunity (i.e. only subjects with humoral impaired immunity may be included).
- The subject has evidence of an active infection at the time of enrolment.
- The subject has previously completed or withdrawn from this study.
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 |
|---|---|---|
| Gammaplex (5%) | Biological | Treatment Sequence 1 - Adults, Treatment Sequence 2 - Adults |
| Gammaplex 10 | Biological | Pediatrics, Treatment Sequence 1 - Adults, Treatment Sequence 2 - Adults |
Primary outcome
Primary Bioequivalence Analysis - Area Under the Curve Within a 28-day Dosing Interval (AUC0-28) in Adult Subjects
Time frame: After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14, 21 and 28 days post-infusion
2 secondary outcomes
Secondary Bioequivalence Analysis - Area Under the Curve Within a 21-Day Dosing Interval (AUC0-21) in Adult Subjects
Time frame: After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14 and 21 days post-infusion
Secondary Bioequivalence Analysis - IgG Trough Levels
Time frame: After a minimum 5 infusions on each product, at pre-infusion.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41773292Geng B, Clark K. Plain language summary: Headache and migraine experiences in people with primary immunodeficiency receiving GAMMAPLEX(R) 5% or 10% intravenous immunoglobulin therapy. Immunotherapy. 2026 Feb;18(2):65-74. doi: 10.1080/1750743X.2026.2633976. Epub 2026 Mar 3.
- Derived from this study: PubMed 39919133Rajendram V, Paddick M, More J. Measles neutralising antibody levels in patients receiving intravenous immunoglobulin treatment - a sub-analysis of a randomized, cross-over bioequivalence trial. PLoS One. 2025 Feb 7;20(2):e0316926. doi: 10.1371/journal.pone.0316926. eCollection 2025.
- Derived from this study: PubMed 39271296Paddick M, Clark K, Wolford E, More J. Protective antibody concentrations in primary immunodeficiency following infusion with 5% or 10% intravenous immunoglobulin. Allergy Asthma Proc. 2024 Nov 1;45(6):414-420. doi: 10.2500/aap.2024.45.240033. Epub 2024 Sep 13.
- Derived from this study: PubMed 36818468Geng B, Clark K, Evangelista M, Wolford E. Low rates of headache and migraine associated with intravenous immunoglobulin infusion using a 15-minute rate escalation protocol in 123 patients with primary immunodeficiency. Front Immunol. 2023 Feb 2;13:1075527. doi: 10.3389/fimmu.2022.1075527. eCollection 2022.
Related trials for Primary Immune Deficiency Disorders
RecruitingObservational study
Natural History of Bronchiectasis
Bronchiectasis, Cystic Fibrosis
RecruitingObservational study
Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Antiretroviral Naive HIV-1 Research Participants
HIV
RecruitingObservational study
Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)
Infections, Pneumonia
RecruitingObservational study
Genetic Basis of Immunodeficiency
Severe Combined Immunodeficiency
RecruitingObservational study
Detection and Characterization of Infections and Infection Susceptibility
Immune Deficiencies
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.
Eric Wolford study director
Bio Products Laboratory
17 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Gammaplex (5%) and Gammaplex 10 in people with Primary Immune Deficiency Disorders and Common Variable Immunodeficiency, run by Bio Products Laboratory at 17 sites in 3 countries.
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 10 inclusion and 27 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 29 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, United Kingdom, Hungary. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Primary Bioequivalence Analysis - Area Under the Curve Within a 28-day Dosing Interval (AUC0-28) in Adult Subjects (time frame: After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14, 21 and 28 days post-infusion). 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 NCT01963143, which also lists 4 linked publications.
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 29 Mar 2017.