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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified June 2015 by Bio Products Laboratory
Sponsor:
Information provided by (Responsible Party):
Bio Products Laboratory
ClinicalTrials.gov Identifier:
NCT01884311
First received: June 14, 2013
Last updated: June 5, 2015
Last verified: June 2015
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: A Phase III, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Subgam®VF in Primary Immunodeficiency Diseases

Resource links provided by NLM:


Further study details as provided by Bio Products Laboratory:

Primary Outcome Measures:
  • Determine the PK profile of Subgam-VF and compare the Area under the curve to a given treatment period (AUC [0-t)]) with historical data all standardized to 1 week at steady state from Gammaplex 5% IGIV Primary Immune studies (GMX01 and GMX04) [ Time Frame: 26 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the safety of Subgam-VF including the incidence of adverse events (AEs) and site infusion reactions in subjects with primary immunodeficiency [ Time Frame: 26 weeks ] [ Designated as safety issue: Yes ]
    Adverse events: Number and percent of infusions associated with 1 or more AEs during the study and specifically AEs that begin during the infusion or within 72 hours after completion of the infusion.

  • To explore PK modelling for alternative dosing schedules [ Time Frame: Week 26 ] [ Designated as safety issue: No ]

Estimated Enrollment: 35
Study Start Date: August 2015
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   2 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01884311

Contacts
Contact: Sarah Jenkins +44 20 895 72293 sarah.jenkins@bpl.co.uk

Locations
United States, California
University of California, Irvine Not yet recruiting
Irvine, California, United States, 92697
Contact: Sudhir Gupta    949-824-5818      
Principal Investigator: Sudhir Gupta         
United States, Colorado
Immunoe International Research Not yet recruiting
Centennial, Colorado, United States, 80112
Contact: Isaac Melamed    303-773-9000      
Principal Investigator: Isaac Melamed         
United States, Florida
Allergy Associate of the Palm Beaches Not yet recruiting
North Palm Beach, Florida, United States, 33408
Contact: Mark Stein    561-626-4561      
Principal Investigator: Mark Stein         
United States, Illinois
Rush University Medical Center Not yet recruiting
Chicago, Illinois, United States, 60612
Contact: James Moy    312-942-6176      
Principal Investigator: James Moy         
United States, North Carolina
Duke University Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: John Sleasman         
Principal Investigator: John Sleasman         
United States, Ohio
Optimed Research Not yet recruiting
Columbus, Ohio, United States, 43235
Contact: Donald McNeil    614-430-8022      
Principal Investigator: Donald McNeil         
United States, Oklahoma
Oklahoma Institute of Allergy & Asthma Clinical Research, LLC Not yet recruiting
Oklahoma City, Oklahoma, United States, 73131
Contact: Amy Darter    405-607-8159      
Principal Investigator: Amy Darter         
United States, Texas
AARA Research Center Not yet recruiting
Dallas, Texas, United States, 75231
Contact: William Lumry    214-373-7374      
Principal Investigator: William Lumry         
Dallas Allergy Immunology Not yet recruiting
Dallas, Texas, United States, 75230
Contact: Richard Wasserman    972-566-7788      
Principal Investigator: Richard Wasserman         
United States, Virginia
O&O Alpan, LLC Not yet recruiting
Fairfax, Virginia, United States, 22030
Contact: Oral Alpan    571-308-1900      
Principal Investigator: Oral Alpan         
United States, Washington
Bellingham Asthma Allergy Clinic Not yet recruiting
Bellingham, Washington, United States, 98225
Contact: David Elkayam    360-733-5733      
Principal Investigator: David Elkayam         
United States, Wisconsin
The Medical College of Wisconsin/Children's Hospital of Wisconsin Not yet recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: John Routes    414-266-6840      
Principal Investigator: John Routes         
Sponsors and Collaborators
Bio Products Laboratory
Investigators
Study Director: Eric Wolford Bio Products Laboratory Limited
  More Information

No publications provided

Responsible Party: Bio Products Laboratory
ClinicalTrials.gov Identifier: NCT01884311     History of Changes
Other Study ID Numbers: SCIG03
Study First Received: June 14, 2013
Last Updated: June 5, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Bio Products Laboratory:
Primary Immune Deficiency Disorders
Common Variable Immunodeficiency
X-linked agammaglobulinaemia
Hyper-IgM Syndrome
Subcutaneous
Immunoglobulins

Additional relevant MeSH terms:
Common Variable Immunodeficiency
Hyper-IgM Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Agammaglobulinemia
Genetic Diseases, X-Linked
Blood Protein Disorders
Dysgammaglobulinemia
Genetic Diseases, Inborn
Hematologic Diseases
Immune System Diseases
Lymphatic Diseases
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on July 07, 2015