search
Back to results

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

Primary Purpose

Primary Immune Deficiency Disorders, Common Variable Immunodeficiency, X-linked Agammaglobulinaemia

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Subgam
Sponsored by
Bio Products Laboratory
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Primary Immune Deficiency Disorders focused on measuring Primary Immune Deficiency Disorders, Common Variable Immunodeficiency, X-linked agammaglobulinaemia, Hyper-IgM Syndrome, Subcutaneous, Immunoglobulins

Eligibility Criteria

2 Years - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Arizona Allergy Associates
  • University of California, Irvine
  • University of California San Diego-- Rady's Children's Hospital
  • Immunoe International Research
  • Allergy Associate of the Palm Beaches
  • Ann and Robert H Lurie Children's Hospital
  • Cardinal Glennon Children's Medical Center
  • Optimed Research
  • Oklahoma Institute of Allergy & Asthma Clinical Research, LLC
  • Pennsylvania State University
  • Dallas Allergy Immunology
  • AARA Research Center
  • University of Utah
  • O&O Alpan, LLC
  • Bellingham Asthma Allergy Clinic
  • The Medical College of Wisconsin/Children's Hospital of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Subgam-VF

Arm Description

Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
June 14, 2013
Last Updated
August 14, 2018
Sponsor
Bio Products Laboratory
search

1. Study Identification

Unique Protocol Identification Number
NCT01884311
Brief Title
Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
Acronym
SCIG03
Official Title
A Phase III, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Subgam-VF in Primary Immunodeficiency Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
August 20, 2015 (Actual)
Primary Completion Date
May 25, 2017 (Actual)
Study Completion Date
May 25, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bio Products Laboratory

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Other
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Subgam-VF
Arm Type
Experimental
Arm Description
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks.
Intervention Type
Biological
Intervention Name(s)
Subgam
Other Intervention Name(s)
Subgam-VF
Intervention Description
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.
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
1 week
Secondary Outcome Measure Information:
Title
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
Description
TEAEs defined as those events with onset date between the first infusion date and 28 days after the last infusion.
Time Frame
30 weeks
Title
Dose Refinement in Switching From Gammaplex 5% IGIV to Subgam-VF
Description
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.
Time Frame
Week 26
Title
Number of Infusion Site Reactions
Description
Infusion site reactions are defined as those events with onset date between the first infusion date and 28 days after the last infusion.
Time Frame
30 weeks
Other Pre-specified Outcome Measures:
Title
Population PK Model for IgG in PID Patients for Alternative Dosing Schedules.
Description
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
Time Frame
30 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: 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%); 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. Exclusion Criteria: 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. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Wolford
Organizational Affiliation
Bio Products Laboratory Limited
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Allergy Associates
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
University of California, Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Facility Name
University of California San Diego-- Rady's Children's Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Immunoe International Research
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Allergy Associate of the Palm Beaches
City
North Palm Beach
State/Province
Florida
ZIP/Postal Code
33408
Country
United States
Facility Name
Ann and Robert H Lurie Children's Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Cardinal Glennon Children's Medical Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
63104
Country
United States
Facility Name
Optimed Research
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Facility Name
Oklahoma Institute of Allergy & Asthma Clinical Research, LLC
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73131
Country
United States
Facility Name
Pennsylvania State University
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
174033
Country
United States
Facility Name
Dallas Allergy Immunology
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
AARA Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
O&O Alpan, LLC
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22030
Country
United States
Facility Name
Bellingham Asthma Allergy Clinic
City
Bellingham
State/Province
Washington
ZIP/Postal Code
98225
Country
United States
Facility Name
The Medical College of Wisconsin/Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs