Primary Immune Deficiency DisordersPhase 3SCIG03NCT01884311
Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
A Phase 3 study testing Subgam in people with Primary Immune Deficiency Disorders and Common Variable Immunodeficiency, run by Bio Products Laboratory at 16 sites in United States.
Trial summary
The main objective of the study is to determine the pharmacokinetics profile of Subgam-VF. The secondary objectives are to assess the safety of Subgam-VF and refine the dose adjustment coefficient for Subgam-VF needed for subjects switching from prior intravenous immunoglobulin (IGIV) therapy. Read more about this study
- Who is it for?
- Ages 2 to 75 years
- Conditions the study is for
- Primary Immune Deficiency Disorders, Common Variable Immunodeficiency, X-linked Agammaglobulinaemia
- What is being tested?
- Subgam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 16 sitesUnited States
- Study dates
- 20 Aug 2015to 25 May 2017
- 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 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Aged between 2 and 75 years (at time of initial consent).
- Body Mass Index (BMI) < 46 for adults (aged 16 years \& older), \& BMI < 28 for children.
- Diagnosed with primary immunodeficiency disease e.g. common variable immunodeficiency, X-linked \& autosomal forms of agammaglobulinaemia, hyper-IgM syndrome, Wiskott-Aldrich syndrome.
- Currently receiving a licensed (or investigational stage III, IIIb) IGIV or SCIG and
- IGIV dose is between 300 and 800 mg/kg/month. SCIG dose is between 110 \& 300 mg/kg/week;
- Dose is stable for at least the past three months (i.e. consistent mg/kg +/- 5%);
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- The infusion interval is every 21 or 28 days for IGIV \& seven days for SCIG;
- Has a documented trough level of ≥ 6 g/L (600 mg/dL) on current IgG therapy. If not available can be obtained at the screening visit, Visit 1 (Week 0).
- Female subjects who are (or become) sexually active must practice contraception by using a method of proven reliability for the duration of the study.
- Females of child-bearing potential, (defined from the onset of menstruation to one year post menopause), must have a negative result on a urine HCG-based pregnancy test.
- Willing to comply with all aspects of the protocol, including blood sampling, for the duration of the study.
- Signed an informed consent form. In the case of subjects under the legal age the parent/guardian will sign an informed consent form \& where appropriate the subject will sign an assent form.
Who cannot join
- Has a history of any severe anaphylactic reaction to blood or any blood-derived product.
- Has selective IgA deficiency or has a history of antibodies to IgA.
- Has clinically significant impairment of cellular or innate immunity at the discretion of the Investigator
- Has evidence of an active infection at the time of enrolment (i.e. on day of first infusion). Subjects who are asymptomatic but have not completed their course of antibiotics are eligible.
- Has previously completed or withdrawn from this study.
- Is currently receiving, or has received, any investigational agent within the prior three months, unless it is an investigational stage III, IIIb IGIV or SCIG.
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- Is pregnant (confirmed by a positive result on an HCG-based pregnancy test) or is nursing.
- Is positive for any of the following at screening:
- Serological test for HIV 1\&2, HCV, or HBsAg
- Has levels at screening greater than 2.5 times the upper limit of normal as defined at the central laboratory of any of the following:
- Alanine transaminase (ALT)
- Aspartate transaminase (AST)
- Has severe renal impairment (defined as serum creatinine greater than two times the upper limit of normal or BUN greater than two times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; or has a history of acute renal failure.
- Is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.
- Has a history of DVT, or thrombotic complications of IgG therapy, or a prior diagnosis of thrombophilia.
- 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, proteinuria) that the Investigator feels may interfere with the conduct of the study.
- Has an acquired medical condition, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (ANC < 1 x 109/L).
- Is receiving the following medication:
- Steroids (long-term daily, > 0.15 mg of prednisone equivalent/kg/day). Requirement for short or intermittent courses of > 0.15mg/kg/day would not exclude a subject.
- Immunosuppressive drugs
- Immunomodulatory drugs
- If ≥ 18 years of age, has non-controlled arterial hypertension (systolic blood pressure > 160 mmHg \&/or diastolic blood pressure > 100 mmHg). For younger subjects refer to current guidelines for diagnosis of blood pressure1.
- Has anemia (hemoglobin < 10 g/dL) at screening.
- Has severe dermatitis that would preclude sites for safe product administration.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Bellingham Asthma Allergy Clinic
Bellingham, Washington, 98225
Immunoe International Research
Centennial, Colorado, 80112
Arizona Allergy Associates
Chandler, Arizona, 85224
Ann and Robert H Lurie Children's Hospital
Chicago, Illinois, 60611
Optimed Research
Columbus, Ohio, 43235
Dallas Allergy Immunology
Dallas, Texas, 75230
AARA Research Center
Dallas, Texas, 75231
O&O Alpan, LLC
Fairfax, Virginia, 22030
Pennsylvania State University
Hershey, Pennsylvania, 174033
University of California, Irvine
Irvine, California, 92697
The Medical College of Wisconsin/Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Cardinal Glennon Children's Medical Center
Minneapolis, Minnesota, 63104
Allergy Associate of the Palm Beaches
North Palm Beach, Florida, 33408
Oklahoma Institute of Allergy & Asthma Clinical Research, LLC
Oklahoma City, Oklahoma, 73131
University of Utah
Salt Lake City, Utah, 84112
University of California San Diego-- Rady's Children's Hospital
San Diego, California, 92123
About this study
Official title: A Phase III, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Subgam-VF in Primary Immunodeficiency Diseases
The main objective of the study is to determine the pharmacokinetics profile of Subgam-VF. The secondary objectives are to assess the safety of Subgam-VF and refine the dose adjustment coefficient for Subgam-VF needed for subjects switching from prior intravenous immunoglobulin (IGIV) therapy.
Read the detailed description
This will be a Phase III, multicenter, open-label, non-randomized study.
Following a screening period, eligible subjects will commence weekly Subgam-VF treatment; this is a 16% subcutaneous IgG product.
Subjects will receive Subgam-VF for 26 weeks during which time safety will be assessed.
After Week 21, PK sampling will commence.
Follow-up visit (one week after the last Subgam-VF infusion, Week 27). All AEs will be monitored up to 28 days after the last Subgam-VF infusion by telephone contact (Week 30).
Subgam-VF will be administered subcutaneously using infusion pumps.
Subjects will be given diaries to record adverse event data as well as any infusions administered at home. In addition there will be a telephone follow up by an appropriately qualified site staff member on day 3 after each site administered and home administered infusion to check for any adverse reactions including infusion site reactions and remind subjects to document these in their subject study diary.
- Conditions
- Primary Immune Deficiency Disorders, Common Variable Immunodeficiency, X-linked Agammaglobulinaemia, Hyperimmunoglobulin M Syndrome
- Being tested
- Subgam
- Keywords
- Primary Immune Deficiency Disorders, Common Variable Immunodeficiency, X-linked agammaglobulinaemia, Hyper-IgM Syndrome, Subcutaneous, Immunoglobulins
- 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.
SubgamBiological
Also called Subgam-VF
Subgam-VF dose will be given as 1.37 of the established IGIV dose (expressed in mg/kg/week) for 26 weeks (26 infusions) beginning one week after the last IGIV infusion. Dose of Subgam-VF will then be adjusted based on the ratio of the Immunoglobulin G (IgG) average concentration achieved with Subgam-VF compared to IGIV.
| Study group | Role | What they receive |
|---|---|---|
| Subgam-VF | Experimental | Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks. Receives: Biological: Subgam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Data (Derived From Absolute Concentration) Were Pooled With Historical Data and a Treatment Variable Defined (Subgam-VF or Gammaplex 5% IGIV). Outcome Measure Defined as Log Transformed sAUC0-t Standardized to One Week.
Log transformed sAUC0-t, (AUC0-t standardized to one week) were analysed using a multiple linear regression model fitted including treatment, allowing for variability between treatment groups. The mean difference (Subgam-VF or Gammaplex IGIV 5%) between treatments with 90% Confidence Interval (CI) were back transformed to give an estimate of the ratio (Subgam-VF/ Gammaplex 5% IGIV) of sAUC(0-t). Data was collected at the following timepoints after week 21 of the clinical trial over a period of 1 week: Pre-dose on Day 0 and post-dose at days 1, 2, 3, 5 and 7.
Measured: 1 week
Secondary outcomes (3)
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
TEAEs defined as those events with onset date between the first infusion date and 28 days after the last infusion.
Measured: 30 weeks
Dose Refinement in Switching From Gammaplex 5% IGIV to Subgam-VF
The initial weekly dose of Subgam-VF administered was calculated by taking the average weekly equivalent of the subject's IGIV dose, divided by the average dosing interval in weeks (i.e. 3 or 4), multiplied by 1.37, a dose adjustment coefficient based on other licensed subcutaneous IgG products. If the subject was already receiving a weekly SCIG IgG there will be no dose adjustment.
A refined dose adjustment was estimated as 1.37/the ratio (Subgam-VF/ Gammaplex 5% IGIV) of geometric means for sAUC0-t and presented with 90% CI.
Measured: Week 26
Number of Infusion Site Reactions
Infusion site reactions are defined as those events with onset date between the first infusion date and 28 days after the last infusion.
Measured: 30 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2013 (estimated)
- Study start20 Aug 2015
- Primary completion25 May 2017
- Study completion25 May 2017
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.
- 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 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 Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01884311
- Sponsor's protocol ID
- SCIG03
- Acronym
- SCIG03
- Status last verified
- Aug 2018
- First submitted
- 14 Jun 2013
- Last updated
- 12 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Subgam-VF in Primary Immunodeficiency Diseases
- ClinicalTrials.gov ID
- NCT01884311
- Acronym / sponsor ID
- SCIG03 / SCIG03
- Conditions
- Primary Immune Deficiency Disorders, Common Variable Immunodeficiency, X-linked Agammaglobulinaemia, Hyperimmunoglobulin M Syndrome
- Keywords
- Primary Immune Deficiency Disorders, Common Variable Immunodeficiency, X-linked agammaglobulinaemia, Hyper-IgM Syndrome, Subcutaneous, Immunoglobulins
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Bio Products LaboratoryUniversity, hospital or other
- Study start
- 20 Aug 2015 (actual)
- Primary completion
- 25 May 2017 (actual)
- Study completion
- 25 May 2017 (actual)
- First posted
- 24 Jun 2013 (estimated)
- Results
- Posted 12 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of the study is to determine the pharmacokinetics profile of Subgam-VF. The secondary objectives are to assess the safety of Subgam-VF and refine the dose adjustment coefficient for Subgam-VF needed for subjects switching from prior intravenous immunoglobulin (IGIV) therapy.
Detailed description
This will be a Phase III, multicenter, open-label, non-randomized study.
Following a screening period, eligible subjects will commence weekly Subgam-VF treatment; this is a 16% subcutaneous IgG product.
Subjects will receive Subgam-VF for 26 weeks during which time safety will be assessed.
After Week 21, PK sampling will commence.
Follow-up visit (one week after the last Subgam-VF infusion, Week 27). All AEs will be monitored up to 28 days after the last Subgam-VF infusion by telephone contact (Week 30).
Subgam-VF will be administered subcutaneously using infusion pumps.
Subjects will be given diaries to record adverse event data as well as any infusions administered at home. In addition there will be a telephone follow up by an appropriately qualified site staff member on day 3 after each site administered and home administered infusion to check for any adverse reactions including infusion site reactions and remind subjects to document these in their subject study diary.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subgam-VF | Experimental | Biological: SubgamSubgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks. |
Who may qualify
- Ages
- 2 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Aged between 2 and 75 years (at time of initial consent).
- Body Mass Index (BMI) < 46 for adults (aged 16 years \& older), \& BMI < 28 for children.
- Diagnosed with primary immunodeficiency disease e.g. common variable immunodeficiency, X-linked \& autosomal forms of agammaglobulinaemia, hyper-IgM syndrome, Wiskott-Aldrich syndrome.
- Currently receiving a licensed (or investigational stage III, IIIb) IGIV or SCIG and
- Female subjects who are (or become) sexually active must practice contraception by using a method of proven reliability for the duration of the study.
Key exclusion criteria (24 listed)
- Has a history of any severe anaphylactic reaction to blood or any blood-derived product.
- Has selective IgA deficiency or has a history of antibodies to IgA.
- Has clinically significant impairment of cellular or innate immunity at the discretion of the Investigator
- Has evidence of an active infection at the time of enrolment (i.e. on day of first infusion). Subjects who are asymptomatic but have not completed their course of antibiotics are eligible.
- 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 |
|---|---|---|
| SubgamAlso: Subgam-VFSubgam-VF dose will be given as 1.37 of the established IGIV dose (expressed in mg/kg/week) for 26 weeks (26 infusions) beginning one week after the last IGIV infusion. Dose of Subgam-VF will then be adjusted based on the ratio of the Immunoglobulin G (IgG) average concentration achieved with Subgam-VF compared to IGIV. | Biological | Subgam-VF |
Primary outcome
Data (Derived From Absolute Concentration) Were Pooled With Historical Data and a Treatment Variable Defined (Subgam-VF or Gammaplex 5% IGIV). Outcome Measure Defined as Log Transformed sAUC0-t Standardized to One Week.
Time frame: 1 week
Log transformed sAUC0-t, (AUC0-t standardized to one week) were analysed using a multiple linear regression model fitted including treatment, allowing for variability between treatment groups. The mean difference (Subgam-VF or Gammaplex IGIV 5%) between treatments with 90% Confidence Interval (CI) were back transformed to give an estimate of the ratio (Subgam-VF/ Gammaplex 5% IGIV) of sAUC(0-t). Data was collected at the following timepoints after week 21 of the clinical trial over a period of 1 week: Pre-dose on Day 0 and post-dose at days 1, 2, 3, 5 and 7.
3 secondary outcomes
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
Time frame: 30 weeks
Dose Refinement in Switching From Gammaplex 5% IGIV to Subgam-VF
Time frame: Week 26
Number of Infusion Site Reactions
Time frame: 30 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Eric Wolford study director
Bio Products Laboratory Limited
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Subgam in people with Primary Immune Deficiency Disorders and Common Variable Immunodeficiency, run by Bio Products Laboratory at 16 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 12 inclusion and 24 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 12 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 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 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 12 Sep 2018). 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?
Data (Derived From Absolute Concentration) Were Pooled With Historical Data and a Treatment Variable Defined (Subgam-VF or Gammaplex 5% IGIV). Outcome Measure Defined as Log Transformed sAUC0-t Standardized to One Week. (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Sep 2018.