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

Study Description

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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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	38 participants
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

Arms and Interventions

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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

Outcome Measures

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Primary Outcome Measures :

1. 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 ]

Secondary Outcome Measures :

1. 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 ]
   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.
2. To explore PK modelling for alternative dosing schedules [ Time Frame: Week 26 ]

Eligibility Criteria

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Ages Eligible for Study:	2 Years to 75 Years (Child, Adult, Senior)
Sexes Eligible for Study:	All
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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

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

Investigators

Study Director:	Eric Wolford	Bio Products Laboratory Limited

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Bio Products Laboratory
ClinicalTrials.gov Identifier:	NCT01884311 History of Changes
Other Study ID Numbers:	SCIG03
First Posted:	June 24, 2013
Last Update Posted:	August 7, 2017
Last Verified:	August 2017

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:

Immunologic Deficiency Syndromes; Common Variable Immunodeficiency; Agammaglobulinemia; Genetic Diseases, X-Linked; Hyper-IgM Immunodeficiency Syndrome; Immune System Diseases; Blood Protein Disorders; Hematologic Diseases	Lymphoproliferative Disorders; Lymphatic Diseases; Genetic Diseases, Inborn; Dysgammaglobulinemia; Immunoglobulins; Immunologic Factors; Physiological Effects of Drugs