SCIG03

Principal Investigator: Karin Chen
Keywords: Immunodeficiency , PID , Subgam Department: Pediatric Administration
IRB Number: 00085874 Co Investigator:  
Specialty: Pediatric Immunology
Sub Specialties:
Recruitment Status: Recruiting

Contact Information

Suzy Jones
Suzy.Jones@hsc.utah.edu
801-585-5067

Brief Summary

This will be a Phase III, multicenter, open-label, non-randomized study. Up to 50 subjects
will be enrolled to ensure 30 evaluable subjects. At least 18 subjects will be adults* (aged 16-
75 years) and 12 will be children split between the age groups 2 to 5 years (i.e. not reached
their 6th birthday), 6 to 11 years (i.e. not reached their 12th birthday) and 12 to 15 years (i.e.
not reached their 16th birthday), 
 
All children who receive at least one infusion of Subgam-VF will be included in the safety analysis. Due to the potential for early withdrawals, PK data may not be available on all 12 children and there may be fewer than 12 evaluable children in the PK analysis. The total number of subjects (adults plus children) evaluable for PK analysis will be at least 30.
 
*The definition of an adult as ≥ 16 years is as per the FDA guidance for PK studies2. Note
this does not affect the requirements for consent/assent, for which each site should follow
their IRB guidelines.
 
This study has two objectives and one exploratory objective:

Primary Objective:

To determine the PK profiled of Subgram-WF and compare the AUC with historical AUC data from Gammaplex 5% IGIV PID studies (GMX01 and GMX04)

Secondary Objective:

       a). To assess the safety of Subgam-VF, including the incidence of adverse events and site infusion reactions in subjects with PID.

       b). To refine the dose adjustment coefficient for Subgam-VF

Exploratory Objective:

To explore PK modelling for alternative dosing schedules. 

 

 

Inclusion 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 and older), and BMI < 28 for children.
 
3) Diagnosed with primary immunodeficiency disease e.g. common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinaemia, hyper-IgM syndrome, Wiskott-Aldrich syndrome.
 
4) Currently receiving a licensed (or investigational stage III, IIIb) IGIV or SCIG and
    a) IGIV dose is between 300 and 800 mg/kg/month. SCIG dose is between 110 and 300                           mg/kg/week;
    b) Dose is stable for at least the past three months (i.e. consistent mg/kg +/- 5%);
    c) The infusion interval is every 21 or 28 days for IGIV and seven days for SCIG;
    d) 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 and where appropriate the subject will sign an assent form.
 
 

Exclusion Criteria

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 and/or diastolic blood pressure > 100 mmHg). For younger subjects refer to current guidelines for diagnosis of blood pressure
 
17) Has anemia (hemoglobin < 10 g/dL) at screening.
 
 
18) Has severe dermatitis that would preclude sites for safe product administration.