Primary ImmunodeficiencyPhase 4KIDSNCT01465958
Pharmacokinetics, Safety, and Tolerability of Subcutaneous GAMUNEX-C in Pediatric Subjects With Primary Immunodeficiency
A Phase 4 study testing GAMUNEX-C in people with Primary Immunodeficiency, run by Grifols Therapeutics LLC at 4 sites in United States.
Trial summary
The purpose of this open-label study is to evaluate the pharmacokinetics, safety, and tolerability of subcutaneously (SC; under the skin) administered GAMUNEX-C compared to intravenously (IV; through the vein) administered GAMUNEX-C in subjects 2-16 years of age with Primary Immunodeficiency. Read more about this study
- Who is it for?
- Ages 2 to 16 years
- Conditions the study is for
- Primary Immunodeficiency
- What is being tested?
- GAMUNEX-C
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 4 sitesUnited States
- Study dates
- Nov 2011to Oct 2013
- Phase
- Phase 4
- 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 16 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Aged 2-16 years old, inclusive.
- Documented and confirmed pre-existing diagnosis of PI with features of hypogammaglobulinemia requiring immunoglobulin replacement.
- Currently on IgG replacement therapy with a serum IgG trough concentration of ≥ 500 mg/dL at the Screening Visit.
- Adequate normal skin to allow for SC infusions.
- Signs an assent form, if applicable (per Institutional Review Board [IRB] requirements). Parent or legal guardian must sign an informed consent form.
- Females of childbearing potential must have a negative urine pregnancy test result and must practice an effective form of contraception (which may include abstinence).
Who cannot join
- History of anaphylaxis or severe systemic response to an immunoglobulin or blood product.
- History of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, recurrent skin infections or other disorders where subcutaneous therapy could be contraindicated.
- Has a specific antibody deficiency disorder, IgG subclass deficiency, or transient hypogammaglobulinemia of infancy.
- History of severe adverse reaction to parenteral products containing immunoglobulin A (IgA).
- Significant proteinuria and/or has a history of acute renal failure and/or severe renal impairment (serum creatinine more than 2.5 times the upper limit of normal [ULN] for age and gender) and/or is on dialysis.
- Known substance or prescription drug abuse in the past 12 months.
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- Acquired medical condition that is known to cause secondary immune deficiency.
- Receiving any of the following medications: systemic corticosteroids (long term daily, >1 mg of prednisone equivalent/kg/day for >30 days) (intermittent courses would not exclude subject); immunosuppressants (i.e., antimetabolites and systemic calcineurin inhibitors; NOTE: inhaled steroids are allowed); or immunomodulators.
- Non-controlled arterial hypertension at a level of ≥ the 90th percentile blood pressure (either systolic or diastolic) for age and height (based on http://www.nhlbi.nih.gov/guidelines/hypertension/child_tbl.pdf ).
- History or current diagnosis of thrombotic episodes; venous thrombus that occurred in association with a medical device > 2 years prior to screening are allowed.
- Currently receiving anti-coagulation therapy.
- History of Kawasaki disease.
- Participated in another clinical trial involving exposure to an investigational product or device within 30 days prior to screening (imaging studies without investigative treatments are permitted) or has received any investigational blood product within the previous 3 months.
- Unable or unwilling to comply with any aspect of the protocol, including blood sampling and completion of the Infusion Site Reactions pages in the SC Infusion Diary.
- In the opinion of the Investigator the subject may have compliance problems with the protocol and the procedures of the protocol.
- Pregnant or lactating.
- Clinical evidence of any significant acute or chronic disease that, in the opinion of the Investigator, may interfere with successful completion of the study.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
IMMUNOe International Research Centers
Centennial, Colorado, 80112
Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021
Childrens Hospital Los Angeles
Los Angeles, California, 90027
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: An Open-label, Single-sequence, Crossover Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Subcutaneous GAMUNEX®-C in Pediatric Subjects With Primary Immunodeficiency
The purpose of this open-label study is to evaluate the pharmacokinetics, safety, and tolerability of subcutaneously (SC; under the skin) administered GAMUNEX-C compared to intravenously (IV; through the vein) administered GAMUNEX-C in subjects 2-16 years of age with Primary Immunodeficiency.
Read the detailed description
This study was a multi-center, open-label, single-sequence, crossover study to evaluate the pharmacokinetics (PK), safety and tolerability of SC-administered GAMUNEX-C in pediatric PI subjects (ages 2-16). The study consisted of a Screening Phase, Run-in Phase, two treatment phases (an IV Phase and a SC Phase), and an End of Study/Early Termination (EOS/ET) visit. Run-in phase: 3 - 4 months, IV Phase: ~ 4 - 5 weeks, SC Phase: 12 weeks, and End of Study/Early Termination (EOS/ET) visit: one week after SC Week #12.
- Conditions
- Primary Immunodeficiency
- Being tested
- GAMUNEX-C
- Medical subject headings
- Primary Immunodeficiency Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GAMUNEX-CBiological
GAMUNEX-C Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified, Intravenous Administration: 200-600 mg/kg per intravenous infusion every 3-4 weeks
GAMUNEX-CBiological
GAMUNEX-C Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified, Subcutaneous Administration: weekly subcutaneous infusion at a mg/kg dose based on subject's intravenous dose and dosing interval x 1.37 conversion factor
| Study group | Role | What they receive |
|---|---|---|
| Intravenous GAMUNEX-C | Active comparator | Not described Receives: Biological: GAMUNEX-C |
| Subcutaneous GAMUNEX-C | Experimental | Not described Receives: Biological: GAMUNEX-C |
What is being measured
The primary outcome is the main question the study is designed to answer.
Steady-state Area Under the Curve (AUC) for Serum Total Immunoglobulin (IgG)
Steady-state area under the curve (AUC): For the IV phase, the mean adjusted AUC was calculated for all 11 subjects, which included subjects on both 3 and 4 week intravenous (IV) dosing schedules and who had sufficient immunoglobulin G (IgG) data. For the SC phase, the mean AUC was calculated for 10 subjects on weekly subcutaneous (SC) administration and who had sufficient IgG data.
Measured: 4 to 5 weeks for IV administration; 12 weeks for SC administration
Mean Trough of Serum Total IgG
Mean trough serum total IgG values were calculated for each subject for the IV Phase (IV #1 and IV #2) and the SC phase (SC Weeks #9 and #12, and End of Treatment/Early termination visit). Mean trough concentration values of serum total IgG during the IV and SC phases were calculated based on the IgG population (subjects who received any amount of study drug and had serum total IgG concentration data).
Measured: 4 - 5 weeks of IV administration and 12 weeks for SC administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2011 (estimated)
- Study startNov 2011
- Primary completionOct 2013
- Study completionOct 2013
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 (1)Papers the sponsor has linked to this study.
- Other trials for Primary ImmunodeficiencyStudies 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grifols Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01465958
- Sponsor's protocol ID
- T5004-401
- Acronym
- KIDS
- Status last verified
- Feb 2015
- First submitted
- 24 Oct 2011
- Last updated
- 13 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Heimall J, Chen J, Church JA, Griffin R, Melamed I, Kleiner GI. Pharmacokinetics, Safety, and Tolerability of Subcutaneous Immune Globulin Injection (Human), 10 % Caprylate/Chromatography Purified (GAMUNEX(R)-C) in Pediatric Patients with Primary Immunodeficiency Disease. J Clin Immunol. 2016 Aug;36(6):600-9. doi: 10.1007/s10875-016-0311-4. Epub 2016 Jun 25.
PubMed 27342758
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Single-sequence, Crossover Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Subcutaneous GAMUNEX®-C in Pediatric Subjects With Primary Immunodeficiency
- ClinicalTrials.gov ID
- NCT01465958
- Acronym / sponsor ID
- KIDS / T5004-401
- Conditions
- Primary Immunodeficiency
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Grifols Therapeutics LLCIndustry (pharma, biotech, devices)
- Study start
- Nov 2011
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 7 Nov 2011 (estimated)
- Results
- Posted 28 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this open-label study is to evaluate the pharmacokinetics, safety, and tolerability of subcutaneously (SC; under the skin) administered GAMUNEX-C compared to intravenously (IV; through the vein) administered GAMUNEX-C in subjects 2-16 years of age with Primary Immunodeficiency.
Detailed description
This study was a multi-center, open-label, single-sequence, crossover study to evaluate the pharmacokinetics (PK), safety and tolerability of SC-administered GAMUNEX-C in pediatric PI subjects (ages 2-16). The study consisted of a Screening Phase, Run-in Phase, two treatment phases (an IV Phase and a SC Phase), and an End of Study/Early Termination (EOS/ET) visit. Run-in phase: 3 - 4 months, IV Phase: ~ 4 - 5 weeks, SC Phase: 12 weeks, and End of Study/Early Termination (EOS/ET) visit: one week after SC Week #12.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous GAMUNEX-C | Active comparator | Biological: GAMUNEX-C |
| Subcutaneous GAMUNEX-C | Experimental | Biological: GAMUNEX-C |
Who may qualify
- Ages
- 2 to 16 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Aged 2-16 years old, inclusive.
- Documented and confirmed pre-existing diagnosis of PI with features of hypogammaglobulinemia requiring immunoglobulin replacement.
- Currently on IgG replacement therapy with a serum IgG trough concentration of ≥ 500 mg/dL at the Screening Visit.
- Adequate normal skin to allow for SC infusions.
- Signs an assent form, if applicable (per Institutional Review Board [IRB] requirements). Parent or legal guardian must sign an informed consent form.
Key exclusion criteria (17 listed)
- History of anaphylaxis or severe systemic response to an immunoglobulin or blood product.
- History of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, recurrent skin infections or other disorders where subcutaneous therapy could be contraindicated.
- Has a specific antibody deficiency disorder, IgG subclass deficiency, or transient hypogammaglobulinemia of infancy.
- History of severe adverse reaction to parenteral products containing immunoglobulin A (IgA).
- Significant proteinuria and/or has a history of acute renal failure and/or severe renal impairment (serum creatinine more than 2.5 times the upper limit of normal [ULN] for age and gender) and/or is on dialysis.
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 |
|---|---|---|
| GAMUNEX-CGAMUNEX-C Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified, Intravenous Administration: 200-600 mg/kg per intravenous infusion every 3-4 weeks | Biological | Intravenous GAMUNEX-C |
| GAMUNEX-CGAMUNEX-C Immune Globulin Injection (Human), 10%, Caprylate/Chromatography Purified, Subcutaneous Administration: weekly subcutaneous infusion at a mg/kg dose based on subject's intravenous dose and dosing interval x 1.37 conversion factor | Biological | Subcutaneous GAMUNEX-C |
Primary outcome
Steady-state Area Under the Curve (AUC) for Serum Total Immunoglobulin (IgG)
Time frame: 4 to 5 weeks for IV administration; 12 weeks for SC administration
Steady-state area under the curve (AUC): For the IV phase, the mean adjusted AUC was calculated for all 11 subjects, which included subjects on both 3 and 4 week intravenous (IV) dosing schedules and who had sufficient immunoglobulin G (IgG) data. For the SC phase, the mean AUC was calculated for 10 subjects on weekly subcutaneous (SC) administration and who had sufficient IgG data.
Mean Trough of Serum Total IgG
Time frame: 4 - 5 weeks of IV administration and 12 weeks for SC administration
Mean trough serum total IgG values were calculated for each subject for the IV Phase (IV #1 and IV #2) and the SC phase (SC Weeks #9 and #12, and End of Treatment/Early termination visit). Mean trough concentration values of serum total IgG during the IV and SC phases were calculated based on the IgG population (subjects who received any amount of study drug and had serum total IgG concentration data).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27342758Heimall J, Chen J, Church JA, Griffin R, Melamed I, Kleiner GI. Pharmacokinetics, Safety, and Tolerability of Subcutaneous Immune Globulin Injection (Human), 10 % Caprylate/Chromatography Purified (GAMUNEX(R)-C) in Pediatric Patients with Primary Immunodeficiency Disease. J Clin Immunol. 2016 Aug;36(6):600-9. doi: 10.1007/s10875-016-0311-4. Epub 2016 Jun 25.
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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.
4 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 GAMUNEX-C in people with Primary Immunodeficiency, run by Grifols Therapeutics LLC at 4 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 6 inclusion and 17 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 13 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
Yes. Results are posted in the registry (first posted 28 Jan 2015). 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?
Steady-state Area Under the Curve (AUC) for Serum Total Immunoglobulin (IgG) (time frame: 4 to 5 weeks for IV administration; 12 weeks for SC administration). The study lists 2 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 NCT01465958, 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 13 Mar 2015.