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

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ClinicalTrials.gov Identifier: NCT01963143
Recruitment Status : Completed
First Posted : October 16, 2013
Results First Posted : March 29, 2017
Last Update Posted : March 29, 2017
Sponsor:
Information provided by (Responsible Party):
Bio Products Laboratory

Tracking Information
First Submitted Date  ICMJE September 13, 2013
First Posted Date  ICMJE October 16, 2013
Results First Submitted Date  ICMJE February 10, 2017
Results First Posted Date  ICMJE March 29, 2017
Last Update Posted Date March 29, 2017
Study Start Date  ICMJE February 2014
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: October 11, 2013)
Primary Bioequivalence Analysis - Area Under the Curve Within a 28-day Dosing Interval (AUC0-28) in Adult Subjects [ Time Frame: Week 15 or 20 and Week 30 or 40 at pre-infusion, 10 minutes before end of infusion, 1,3,6,24,48,84 hours, 14, 21 and 28 days post-infusion ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
  • 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 ]
  • Secondary Bioequivalence Analysis - IgG Trough Levels [ Time Frame: After a minimum 5 infusions on each product, at pre-infusion. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 11, 2013)
  • Secondary Bioequivalence analysis - IgG trough levels [ Time Frame: Week 15 or 20 and Week 30 or 40 at pre-infusion, 10 minutes before end of infusion, 1,3,6,24,48,84 hours, 14, 21 and 28 days post-infusion ]
  • Other pharmacokinetic parameters for IgG [ Time Frame: Week 15 or 20 and Week 30 or 40 at pre-infusion, 10 minutes before end of infusion, 1,3,6,24,48,84 hours, 14, 21 and 28 days post-infusion ]
    AUC0-τ - area under the concentration versus time curve within a dosing interval
  • Adverse events [ Time Frame: Up to 10 months ]
    The number and percent of infusions associated with one or more adverse events (AEs) (irrespective of causality) that begin during the infusion or within 72 hours after completion of the infusion will be calculated
  • Adverse events - Thrombotic events [ Time Frame: Up to 10 months ]
    Number of thrombotic events
  • Adverse events - product-related AEs [ Time Frame: Up to 10 months ]
    Nature, severity, and frequency of product-related AEs
  • Adverse events - SUSARS [ Time Frame: Up to 10 months ]
    Number of Suspected unexpected serious adverse reactions (SUSARS)
  • Vital signs [ Time Frame: Screening and every 21 or 28 days during the study. Also 7 days after the first infusion in each treatment phase. ]
    Clinically significant changes in vitals signs will be classified as adverse events
  • Laboratory testing [ Time Frame: Screening and every 21 or 28 days during the study. Also 7 days after the first infusion in each treatment phase. ]
    Clinically significant changes in laboratory tests, hematology, clinical chemistry
  • Viral transmission [ Time Frame: Screening, Weeks 3 or 4, Weeks 4 or 5, Weeks 18 or 24, Weeks 19 or 25 and end of study (Weeks 34 or 44) ]
    Tests for Hepatitis B (HBV), Hepatitis C (HCV), Human immunodeficiency virus (HIV), and Parvovirus B19
  • Physical Examination [ Time Frame: Screening and every 21 or 28 days during the study. Also 7 days after the first infusion in each treatment phase. ]
    Physical examination will be recorded by body system. Clinically significant changes from baseline in any body system will be classified as adverse events.
  • Tests for hemolysis [ Time Frame: Weeks 3 or 4, Weeks 4 or 5, Weeks 6 or 8 and Weeks 18 or 24, Weeks 19 or 25, Weeks 21 or 28 and end of study (Week 34 or 44) ]
    Direct Coombs' test
  • Other pharmacokinetic parameters for IgG [ Time Frame: Week 15 or 20 and Week 30 or 40 at pre-infusion, 10 minutes before end of infusion, 1,3,6,24,48,84 hours, 14, 21 and 28 days post-infusion ]
    Cmax - peak concentration in plasma tmax - time to reach the peak concentration in plasma
  • Other pharmacokinetic parameters for IgG [ Time Frame: Week 15 or 20 and Week 30 or 40 at pre-infusion, 10 minutes before end of infusion, 1,3,6,24,48,84 hours, 14, 21 and 28 days post-infusion ]
    t1/2 - apparent terminal half-life
  • Other pharmacokinetic parameters for IgG [ Time Frame: Week 15 or 20 and Week 30 or 40 at pre-infusion, 10 minutes before end of infusion, 1,3,6,24,48,84 hours, 14, 21 and 28 days post-infusion ]
    CL - systemic clearance
  • Tests for hemolysis [ Time Frame: Weeks 3 or 4, Weeks 4 or 5, Weeks 6 or 8 and Weeks 18 or 24, Weeks 19 or 25, Weeks 21 or 28 and end of study (Week 34 or 44) ]
    Tests for haptoglobin
  • Tests for hemolysis [ Time Frame: Weeks 3 or 4, Weeks 4 or 5, Weeks 6 or 8 and Weeks 18 or 24, Weeks 19 or 25, Weeks 21 or 28 and end of study (Week 34 or 44) ]
    plasma free hemoglobin
  • Tests for hemolysis [ Time Frame: Weeks 3 or 4, Weeks 4 or 5, Weeks 6 or 8 and Weeks 18 or 24, Weeks 19 or 25, Weeks 21 or 28 and end of study (Week 34 or 44) ]
    Urine hemosiderin
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Primary Immune Deficiency Disorders
  • Common Variable Immunodeficiency
  • X-linked Agammaglobulinaemia
  • Hyper-IgM Syndrome
Intervention  ICMJE
  • Biological: Gammaplex (5%)
  • Biological: Gammaplex 10
Study Arms  ICMJE
  • Experimental: Treatment Sequence 1 - Adults
    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
    Interventions:
    • Biological: Gammaplex (5%)
    • Biological: Gammaplex 10
  • Experimental: Treatment Sequence 2 - Adults
    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
    Interventions:
    • Biological: Gammaplex (5%)
    • Biological: Gammaplex 10
  • Experimental: Pediatrics
    Gammaplex 10 - 5 intravenous infusions at a dose of 300 to 800 mg/kg/infusion, given every 21 to 28 days
    Intervention: Biological: Gammaplex 10
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 11, 2013)
48
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE May 2016
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 55 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Hungary,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01963143
Other Study ID Numbers  ICMJE GMX07
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bio Products Laboratory
Study Sponsor  ICMJE Bio Products Laboratory
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Eric Wolford Bio Products Laboratory
PRS Account Bio Products Laboratory
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP