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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:
Sponsor: Bio Products Laboratory

Current Primary Outcome: 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: 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 ]

Current Secondary Outcome:

• 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:

• 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

Information By: Bio Products Laboratory

Dates:
Date Received: September 13, 2013
Date Started: February 2014
Date Completion:
Last Updated: February 10, 2017
Last Verified: February 2017