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Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases (GMX07)

Primary Purpose

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

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Gammaplex (5%)
Gammaplex 10
Sponsored by
Bio Products Laboratory
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Immune Deficiency Disorders

Eligibility Criteria

2 Years - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  1. Adult cohort: The subject is aged 16 to 55 years inclusive, is of either sex, and belongs to any ethnic group.

    Pediatric cohort: The subject is aged 2 to 15 years inclusive, is of either sex, weighs at least 10 kg, and belongs to any ethnic group.

  2. The subject has primary immunodeficiency disease, e.g. common variable immunodeficiency, X linked and autosomal forms of agammaglobulinemia, hyper IgM (Immunoglobulin M) syndrome. Isolated deficiency of a single IgG subclass or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion.
  3. The subject is currently receiving a licensed IGIV (or investigational stage III, IIIb IGIV) at a dose that has not changed by ± 50% of the mean dose for at least three months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be either every 21 or every 28 days.
  4. The subject must have a trough level ≥ 6 g/L (600 mg/dL). At least one documented trough level must be available from the three months before Screening.
  5. The subject must have documentation from the last three consecutive routine IGIV infusions for the following, before the first infusion in this study: dose of IGIV, treatment intervals, and trade name (or identity) of the IGIV treatment.
  6. Female subjects of childbearing potential must have a negative result on an HCG (human chorionic gonadotropin) based pregnancy test at Screening.
  7. Females who are or become sexually active must practice contraception using a method of proven reliability for the study duration.
  8. The subject is willing to comply with all aspects of the protocol for the duration of the study.
  9. The subject has signed an informed consent form and assent form (if applicable).

Exclusion criteria:

  1. The subject has a history of any severe anaphylactic reaction to blood or any blood derived product.
  2. The subject has selective IgA deficiency, history of reaction to products containing IgA (Immunoglobulin A), or has a history of antibodies to IgA.
  3. The subject has cellular or innate impaired immunity (i.e. only subjects with humoral impaired immunity may be included).
  4. The subject has evidence of an active infection at the time of enrolment.
  5. The subject has previously completed or withdrawn from this study.
  6. The subject is currently receiving, or has received, any investigational agent other than an IGIV within the prior three months.
  7. The subject is pregnant or is nursing.
  8. The subject has positive results for any of the following at Screening:

    • Serological test for HIV 1 and 2, HCV, or HBsAg
    • NAT (Nucleic acid amplification technique)for HCV
    • NAT for HIV
  9. The subject has levels > 2.5 times the upper limit of normal, as defined at the central laboratory, of any of the following at Screening:

    • Alanine amino transaminase
    • Aspartate amino transaminase
  10. The subject has severe renal impairment (defined as serum creatinine greater than two times the upper limit of normal or blood urea nitrogen greater than 2.5 times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; the subject has a history of acute renal failure.
  11. The subject is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months.
  12. The subject has a history of deep vein thrombosis or thrombotic complications of IGIV therapy.
  13. The subject 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) that the Investigator feels may interfere with the conduct of the study.
  14. The subject has an acquired immunodeficiency condition such as chronic* lymphocytic leukemia, lymphoma, multiple myeloma, or chronic or recurrent neutropenia (absolute neutrophil count < 1 × 109/L).
  15. The subject is receiving the following medication:

    • Steroids (long term daily, ≥ 0.15 mg of prednisone equivalent/kg/day). Requirement for short or intermittent courses of steroids would not exclude a subject.
    • Immunosuppressive drugs
    • Immunomodulatory drugs
  16. The subject has uncontrolled arterial hypertension (systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg).
  17. The subject has anemia (hemoglobin < 10 g/dL) at Screening.
  18. The subject is known to be intolerant to any component of Gammaplex, such as sorbitol (i.e. hereditary intolerance to fructose) or glycine.

    • Chronic conditions would be as per the Investigator's opinion however for this study the guidance is that the condition has been present for at least 6 months.

Sites / Locations

  • Arizona Allergy Associates
  • Miller Children's Hospital
  • UCLA Medical Center
  • Childrens Hospital Los Angeles
  • IMMUNOe International Research Centers
  • Joe DiMaggio Children's Hospital
  • Allergy Associates of the Palm Beaches, PA
  • Rush University Medical Center
  • Institute for Asthma and Allergy
  • Asthma and Allergy Center
  • Dallas Allergy Immunology Research
  • University of Utah Primary Children's Hospital
  • O&O Alpan, LLC
  • Bellingham Asthma Allergy and Immunology Clinic
  • Egyesitett Szent Istvan es Szent Laszlo Korhaz
  • University Hospital of Wales
  • The Royal Free Hospital and Medical School

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Treatment Sequence 1 - Adults

Treatment Sequence 2 - Adults

Pediatrics

Arm Description

Gammaplex 5% - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days, followed by Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days

Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days, followed by Gammaplex 5% - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days

Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days

Outcomes

Primary Outcome Measures

Primary Bioequivalence Analysis - Area Under the Curve Within a 28-day Dosing Interval (AUC0-28) in Adult Subjects

Secondary Outcome Measures

Secondary Bioequivalence Analysis - Area Under the Curve Within a 21-Day Dosing Interval (AUC0-21) in Adult Subjects
Secondary Bioequivalence Analysis - IgG Trough Levels

Full Information

First Posted
September 13, 2013
Last Updated
February 10, 2017
Sponsor
Bio Products Laboratory
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1. Study Identification

Unique Protocol Identification Number
NCT01963143
Brief Title
Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
Acronym
GMX07
Official Title
A Phase III, Multicenter, Open-label, Randomized, Two-Period, Crossover Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
February 2014 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
May 2016 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The primary objective is to demonstrate the bioequivalence of Gammaplex® 10 intravenous immunoglobulin (IGIV) and Gammaplex® 5% IGIV with respect to area under the curve within a 28-day dosing interval (AUC0-28) in a cohort of adult subjects. The secondary objectives are to demonstrate the bioequivalence of Gammaplex® 10 IGIV and Gammaplex® 5% IGIV with respect to area under the curve within a 21-day dosing interval (AUC0-21) in adult subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV and Gammaplex 5% IGIV including Immunoglobulin G (IgG) trough levels and to investigate the safety and tolerability of Gammaplex 10 IGIV and Gammaplex 5% IGIV in adults subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV including IgG trough levels and to investigate the safety and tolerability of Gammaplex 10 IGIV in pediatric subjects.

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, Hyper-IgM Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Sequence 1 - Adults
Arm Type
Experimental
Arm Description
Gammaplex 5% - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days, followed by Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days
Arm Title
Treatment Sequence 2 - Adults
Arm Type
Experimental
Arm Description
Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days, followed by Gammaplex 5% - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days
Arm Title
Pediatrics
Arm Type
Experimental
Arm Description
Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days
Intervention Type
Biological
Intervention Name(s)
Gammaplex (5%)
Intervention Type
Biological
Intervention Name(s)
Gammaplex 10
Primary Outcome Measure Information:
Title
Primary Bioequivalence Analysis - Area Under the Curve Within a 28-day Dosing Interval (AUC0-28) in Adult Subjects
Time Frame
After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14, 21 and 28 days post-infusion
Secondary Outcome Measure Information:
Title
Secondary Bioequivalence Analysis - Area Under the Curve Within a 21-Day Dosing Interval (AUC0-21) in Adult Subjects
Time Frame
After a minimum 5 infusions on each product, at pre-infusion, 10 minutes before end of infusion, 1, 3, 6, 24, 48 hours, 4, 7, 14 and 21 days post-infusion
Title
Secondary Bioequivalence Analysis - IgG Trough Levels
Time Frame
After a minimum 5 infusions on each product, at pre-infusion.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: Adult cohort: The subject is aged 16 to 55 years inclusive, is of either sex, and belongs to any ethnic group. Pediatric cohort: The subject is aged 2 to 15 years inclusive, is of either sex, weighs at least 10 kg, and belongs to any ethnic group. The subject has primary immunodeficiency disease, e.g. common variable immunodeficiency, X linked and autosomal forms of agammaglobulinemia, hyper IgM (Immunoglobulin M) syndrome. Isolated deficiency of a single IgG subclass or of specific antibodies without hypogammaglobulinemia per se, does not qualify for inclusion. The subject is currently receiving a licensed IGIV (or investigational stage III, IIIb IGIV) at a dose that has not changed by ± 50% of the mean dose for at least three months before study entry and is between 300 and 800 mg/kg/infusion. The infusion interval must be either every 21 or every 28 days. The subject must have a trough level ≥ 6 g/L (600 mg/dL). At least one documented trough level must be available from the three months before Screening. The subject must have documentation from the last three consecutive routine IGIV infusions for the following, before the first infusion in this study: dose of IGIV, treatment intervals, and trade name (or identity) of the IGIV treatment. Female subjects of childbearing potential must have a negative result on an HCG (human chorionic gonadotropin) based pregnancy test at Screening. Females who are or become sexually active must practice contraception using a method of proven reliability for the study duration. The subject is willing to comply with all aspects of the protocol for the duration of the study. The subject has signed an informed consent form and assent form (if applicable). Exclusion criteria: The subject has a history of any severe anaphylactic reaction to blood or any blood derived product. The subject has selective IgA deficiency, history of reaction to products containing IgA (Immunoglobulin A), or has a history of antibodies to IgA. The subject has cellular or innate impaired immunity (i.e. only subjects with humoral impaired immunity may be included). The subject has evidence of an active infection at the time of enrolment. The subject has previously completed or withdrawn from this study. The subject is currently receiving, or has received, any investigational agent other than an IGIV within the prior three months. The subject is pregnant or is nursing. The subject has positive results for any of the following at Screening: Serological test for HIV 1 and 2, HCV, or HBsAg NAT (Nucleic acid amplification technique)for HCV NAT for HIV The subject has levels > 2.5 times the upper limit of normal, as defined at the central laboratory, of any of the following at Screening: Alanine amino transaminase Aspartate amino transaminase The subject has severe renal impairment (defined as serum creatinine greater than two times the upper limit of normal or blood urea nitrogen greater than 2.5 times the upper limit of normal for the range of the laboratory doing the analysis); the subject is on dialysis; the subject has a history of acute renal failure. The subject is known to abuse alcohol, opiates, psychotropic agents, or other chemicals or drugs, or has done so within the past 12 months. The subject has a history of deep vein thrombosis or thrombotic complications of IGIV therapy. The subject 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) that the Investigator feels may interfere with the conduct of the study. The subject has an acquired immunodeficiency condition such as chronic* lymphocytic leukemia, lymphoma, multiple myeloma, or chronic or recurrent neutropenia (absolute neutrophil count < 1 × 109/L). The subject is receiving the following medication: Steroids (long term daily, ≥ 0.15 mg of prednisone equivalent/kg/day). Requirement for short or intermittent courses of steroids would not exclude a subject. Immunosuppressive drugs Immunomodulatory drugs The subject has uncontrolled arterial hypertension (systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg). The subject has anemia (hemoglobin < 10 g/dL) at Screening. The subject is known to be intolerant to any component of Gammaplex, such as sorbitol (i.e. hereditary intolerance to fructose) or glycine. Chronic conditions would be as per the Investigator's opinion however for this study the guidance is that the condition has been present for at least 6 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Wolford
Organizational Affiliation
Bio Products Laboratory
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
Miller Children's Hospital
City
Long Beach,
State/Province
California
ZIP/Postal Code
90806
Country
United States
Facility Name
UCLA Medical Center
City
Los Angeles,
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Childrens Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
IMMUNOe International Research Centers
City
Centennial
State/Province
Colorado
ZIP/Postal Code
80112
Country
United States
Facility Name
Joe DiMaggio Children's Hospital
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33021
Country
United States
Facility Name
Allergy Associates of the Palm Beaches, PA
City
N Palm Beach
State/Province
Florida
ZIP/Postal Code
33408
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Institute for Asthma and Allergy
City
Chevy Chase
State/Province
Maryland
ZIP/Postal Code
20815
Country
United States
Facility Name
Asthma and Allergy Center
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43617
Country
United States
Facility Name
Dallas Allergy Immunology Research
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
University of Utah Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
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 and Immunology Clinic
City
Bellingham
State/Province
Washington
ZIP/Postal Code
98225
Country
United States
Facility Name
Egyesitett Szent Istvan es Szent Laszlo Korhaz
City
Budapest
Country
Hungary
Facility Name
University Hospital of Wales
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
The Royal Free Hospital and Medical School
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases

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