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Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases (SCIG03)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01884311
Recruitment Status : Completed
First Posted : June 24, 2013
Results First Posted : September 12, 2018
Last Update Posted : September 12, 2018
Information provided by (Responsible Party):
Bio Products Laboratory

Brief 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.

Condition or disease Intervention/treatment Phase
Primary Immune Deficiency Disorders Common Variable Immunodeficiency X-linked Agammaglobulinaemia Hyperimmunoglobulin M Syndrome Biological: Subgam Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase III, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Subgam-VF in Primary Immunodeficiency Diseases
Actual Study Start Date : August 20, 2015
Actual Primary Completion Date : May 25, 2017
Actual Study Completion Date : May 25, 2017

Arm Intervention/treatment
Experimental: Subgam-VF
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks.
Biological: Subgam
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.
Other Name: Subgam-VF

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs) [ Time Frame: 30 weeks ]
    TEAEs defined as those events with onset date between the first infusion date and 28 days after the last infusion.

  2. Dose Refinement in Switching From Gammaplex 5% IGIV to Subgam-VF [ Time Frame: Week 26 ]

    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.

  3. Number of Infusion Site Reactions [ Time Frame: 30 weeks ]
    Infusion site reactions are defined as those events with onset date between the first infusion date and 28 days after the last infusion.

Other Outcome Measures:
  1. Population PK Model for IgG in PID Patients for Alternative Dosing Schedules. [ Time Frame: 30 months ]

    Develop a population pharmacokinetic (PK) model for IgG in PID patients following IV (Gammaplex 5%) or SC (Subgam-VF) administration;

    • Conduct a formal covariate analysis to assess the impact of patient demographics, and disease-related factors on the PK of IgG following IV or SC administration and to identify those patient covariates which may be utilized in or require dose adjustment;
    • Use the final population PK model to simulate serum IgG concentration-time profiles in a population of PID patients in order to:

      • Assess switching from various IgG IV and SC dosing regimens; and
      • Derive the weight-adjusted dose increment required to achieve a specified difference in serum IgG trough levels when Subgam-VF is administered either weekly or biweekly

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Aged between 2 and 75 years (at time of initial consent).
  2. Body Mass Index (BMI) < 46 for adults (aged 16 years & older), & BMI < 28 for children.
  3. Diagnosed with primary immunodeficiency disease e.g. common variable immunodeficiency, X-linked & autosomal forms of agammaglobulinaemia, hyper-IgM syndrome, Wiskott-Aldrich syndrome.
  4. Currently receiving a licensed (or investigational stage III, IIIb) IGIV or SCIG and

    1. IGIV dose is between 300 and 800 mg/kg/month. SCIG dose is between 110 & 300 mg/kg/week;
    2. Dose is stable for at least the past three months (i.e. consistent mg/kg +/- 5%);
    3. The infusion interval is every 21 or 28 days for IGIV & seven days for SCIG;
    4. 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).
  5. Female subjects who are (or become) sexually active must practice contraception by using a method of proven reliability for the duration of the study.
  6. 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.
  7. Willing to comply with all aspects of the protocol, including blood sampling, for the duration of the study.
  8. 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.

Exclusion Criteria:

  1. Has a history of any severe anaphylactic reaction to blood or any blood-derived product.
  2. Has selective IgA deficiency or has a history of antibodies to IgA.
  3. Has clinically significant impairment of cellular or innate immunity at the discretion of the Investigator
  4. 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.
  5. Has previously completed or withdrawn from this study.
  6. 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.
  7. Is pregnant (confirmed by a positive result on an HCG-based pregnancy test) or is nursing.
  8. Is positive for any of the following at screening:

    • Serological test for HIV 1&2, HCV, or HBsAg

  9. 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)
  10. 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.
  11. Is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.
  12. Has a history of DVT, or thrombotic complications of IgG therapy, or a prior diagnosis of thrombophilia.
  13. 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.
  14. Has an acquired medical condition, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (ANC < 1 x 109/L).
  15. 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
  16. 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.
  17. Has anemia (hemoglobin < 10 g/dL) at screening.
  18. Has severe dermatitis that would preclude sites for safe product administration.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01884311

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United States, Arizona
Arizona Allergy Associates
Chandler, Arizona, United States, 85224
United States, California
University of California, Irvine
Irvine, California, United States, 92697
University of California San Diego-- Rady's Children's Hospital
San Diego, California, United States, 92123
United States, Colorado
Immunoe International Research
Centennial, Colorado, United States, 80112
United States, Florida
Allergy Associate of the Palm Beaches
North Palm Beach, Florida, United States, 33408
United States, Illinois
Ann and Robert H Lurie Children's Hospital
Chicago, Illinois, United States, 60611
United States, Minnesota
Cardinal Glennon Children's Medical Center
Minneapolis, Minnesota, United States, 63104
United States, Ohio
Optimed Research
Columbus, Ohio, United States, 43235
United States, Oklahoma
Oklahoma Institute of Allergy & Asthma Clinical Research, LLC
Oklahoma City, Oklahoma, United States, 73131
United States, Pennsylvania
Pennsylvania State University
Hershey, Pennsylvania, United States, 174033
United States, Texas
Dallas Allergy Immunology
Dallas, Texas, United States, 75230
AARA Research Center
Dallas, Texas, United States, 75231
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
United States, Virginia
O&O Alpan, LLC
Fairfax, Virginia, United States, 22030
United States, Washington
Bellingham Asthma Allergy Clinic
Bellingham, Washington, United States, 98225
United States, Wisconsin
The Medical College of Wisconsin/Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Bio Products Laboratory
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Study Director: Eric Wolford Bio Products Laboratory Limited
  Study Documents (Full-Text)

Documents provided by Bio Products Laboratory:
Study Protocol  [PDF] March 22, 2017
Statistical Analysis Plan  [PDF] January 12, 2017

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Responsible Party: Bio Products Laboratory Identifier: NCT01884311    
Other Study ID Numbers: SCIG03
First Posted: June 24, 2013    Key Record Dates
Results First Posted: September 12, 2018
Last Update Posted: September 12, 2018
Last Verified: August 2018
Keywords provided by Bio Products Laboratory:
Primary Immune Deficiency Disorders
Common Variable Immunodeficiency
X-linked agammaglobulinaemia
Hyper-IgM Syndrome
Additional relevant MeSH terms:
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Hyper-IgM Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Common Variable Immunodeficiency
Immune System Diseases
Blood Protein Disorders
Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Genetic Diseases, Inborn