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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Bio Products Laboratory
Sponsor:
Information provided by (Responsible Party):
Bio Products Laboratory
ClinicalTrials.gov Identifier:
NCT01963143
First received: September 13, 2013
Last updated: August 19, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Primary Immune Deficiency Disorders
Common Variable Immunodeficiency
X-linked Agammaglobulinaemia
Hyper-IgM Syndrome
Biological: Gammaplex (5%)
Biological: Gammaplex 10
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bio Products Laboratory:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    AUC0-τ - area under the concentration versus time curve within a dosing interval

  • Adverse events [ Time Frame: Up to 10 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Number of thrombotic events

  • Adverse events - product-related AEs [ Time Frame: Up to 10 months ] [ Designated as safety issue: Yes ]
    Nature, severity, and frequency of product-related AEs

  • Adverse events - SUSARS [ Time Frame: Up to 10 months ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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. ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    Urine hemosiderin


Estimated Enrollment: 48
Study Start Date: February 2014
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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
Biological: Gammaplex 10

  Eligibility

Ages Eligible for Study:   2 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01963143

Locations
United States, Arizona
Arizona Allergy Associates Not yet recruiting
Chandler, Arizona, United States, 85224
Contact: Linda Lentini, RN    480-850-2872    Linda_L@azallergy.com   
Principal Investigator: Duane Wong, MD         
United States, California
Childrens Hospital Los Angeles Not yet recruiting
Los Angeles, California, United States, 90027
Contact: Dalila Ortega    323-361-4537    Dlopez@chla.usc.edu   
Principal Investigator: Joseph Church, MD         
UCLA Medical Center Not yet recruiting
Los Angeles,, California, United States, 90095
Contact: Stephanie Okimoto    310-267-1040    Sokimoto@mednet.ucla.edu   
Principal Investigator: Robert Roberts, MD         
United States, Colorado
IMMUNOe International Research Centers Recruiting
Centennial, Colorado, United States, 80112
Contact: Maninder Sethi    303-224-4673    msethi@immunoe.com   
Principal Investigator: Isaac Melamed, MD         
United States, Florida
Joe DiMaggio Children's Hospital Not yet recruiting
Hollywood, Florida, United States, 33021
Contact: Paulette Smith, RN, BSN    954-265-6388    Psmith@mhs.net   
Principal Investigator: Gary Kleiner, MD         
Allergy Associates of the Palm Beaches, PA Recruiting
N Palm Beach, Florida, United States, 33408
Contact: Kelly Farnan    561-626-4561    kellyfarnan@pballergy.com   
Principal Investigator: Mark Stein, MD         
Sarasota Clinical Research Recruiting
Sarasota, Florida, United States, 34233
Contact: Sally Kastes    941-927-4888    research@windomallergy.com   
Principal Investigator: Hugh Windom, MD         
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Grace Li    312-942-8701    Jia_li@rush.edu   
Contact: Samantha N Zitzer    312-563-4178    Samantha_N_Zitzer@Rush.edu   
Principal Investigator: James Moy, MD         
United States, Maryland
Institute for Asthma and Allergy Recruiting
Chevy Chase, Maryland, United States, 20815
Contact: Lakeesha Kosh    301-986-0670    iaaresearchlakeesha@gmail.com   
Principal Investigator: Michael Kaliner, MD         
United States, Ohio
Asthma and Allergy Center Recruiting
Toledo, Ohio, United States, 43617
Contact: Patricia Bak    419-843-8815    coral_expressions@yahoo.com   
Principal Investigator: Syed Rehman, MD         
United States, Texas
Dallas Allergy Immunology Research Recruiting
Dallas, Texas, United States, 75230
Contact: Rebecca Martin    972-566-6801    rebecca.martin@dallasallergy.net   
Principal Investigator: Richard Wasserman, MD         
Allergy Asthma & Immunology Clinic PA Recruiting
Irving, Texas, United States, 75063
Contact: Catherine Perkins    214-254-4395    catherine@dsallergy.com   
Principal Investigator: Daniel Suez, MD         
United States, Virginia
O&O Alpan, LLC Recruiting
Fairfax,, Virginia, United States, 22030
Contact: Chidima Ioanou    571-308-1905      
Principal Investigator: Oral Alpan, MD         
United States, Washington
Bellingham Asthma Allergy and Immunology Clinic Recruiting
Bellingham, Washington, United States, 98225
Contact: Jill Elkayam    360-733-7533    jselkayam@hinet.org   
Principal Investigator: David Elkayam, MD         
United Kingdom
University Hospital of Wales Recruiting
Cardiff, Wales, United Kingdom, CF14 4XW
Contact: Emily Carne    +44 2920745814    Emily.Carne@wales.nhs.uk   
Principal Investigator: Stephen Jolles, MD         
The Royal Free Hospital and Medical School Recruiting
London, United Kingdom, NW3 2QG
Contact: Sarita Workman    +44 20 7794 0500 ext 33832    sarita.workman@nhs.net   
Principal Investigator: Ronnie Chee, MD         
Sponsors and Collaborators
Bio Products Laboratory
Investigators
Study Director: Tim J. Aldwinckle, MD Bio Products Laboratory
  More Information

No publications provided

Responsible Party: Bio Products Laboratory
ClinicalTrials.gov Identifier: NCT01963143     History of Changes
Other Study ID Numbers: GMX07
Study First Received: September 13, 2013
Last Updated: August 19, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hyper-IgM Immunodeficiency Syndrome
Hyper-IgM Immunodeficiency Syndrome, Type 1
Immunologic Deficiency Syndromes
Agammaglobulinemia
Common Variable Immunodeficiency
Genetic Diseases, X-Linked
Blood Protein Disorders
Dysgammaglobulinemia
Genetic Diseases, Inborn
Hematologic Diseases
Immune System Diseases
Lymphatic Diseases
Lymphoproliferative Disorders
Immunoglobulins, Intravenous
Rho(D) Immune Globulin
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014