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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase III, Multicenter, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Subgam-VF in Primary Immunodeficiency Diseases

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 Summary:

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.


Sponsor: Bio Products Laboratory

Current Primary Outcome: Determine the PK profile of Subgam-VF and compare the Area under the curve to a given treatment period (AUC [0-t)]) with historical data all standardized to 1 week at steady state from Gammaplex 5% IGIV Primary Immune studies (GMX01 and GMX04) [ Time Frame: 26 weeks ]

Original Primary Outcome: Number of serious bacterial infections (SBIs) per subject per year [ Time Frame: 12 months ]

Current Secondary Outcome:

  • Assess the safety of Subgam-VF including the incidence of adverse events (AEs) and site infusion reactions in subjects with primary immunodeficiency [ Time Frame: 26 weeks ]
    Adverse events: Number and percent of infusions associated with 1 or more AEs during the study and specifically AEs that begin during the infusion or within 72 hours after completion of the infusion.
  • To explore PK modelling for alternative dosing schedules [ Time Frame: Week 26 ]


Original Secondary Outcome:

  • Average concentration at steady state (Cav) and IgG trough levels determined at steady state [ Time Frame: Week 26 ]
  • Dose of Subgam-VF [ Time Frame: Week 26 ]
    Dose of Subgam-VF per week needed to maintain the Cav at a value that is not inferior to that with IGIV
  • Trough serum IgG levels [ Time Frame: Screening and Routine IgG, Weeks 1-4,10, 11, 13, 17, 21, 36, 41, 46, 51 and 61 ]
    Trough serum IgG levels (measured before every infusion administered at the study site and certain visits at home)
  • IgG subclasses [ Time Frame: Weeks 1, 13, 21, 41, 51 and 61 ]
  • Other pharmacokinetic parameters for IgG [ Time Frame: Screening and Routine IgG, Weeks 10-11, 26-27 ]
    AUC(0-t )- area under the plasma concentration-time curve of the dosing period; Cmax - maximum concentration in plasma; tmax - time to reach the maximum concentration in plasma
  • Therapeutic efficacy: Number of infection episodes [ Time Frame: 12 months ]
  • Therapeutic efficacy: Number of episodes of fever [ Time Frame: 12 months ]
  • Therapeutic efficacy: Number of days missed from work/school/day care or inability to perform normal activities due to infections [ Time Frame: 12 months ]
  • Therapeutic efficacy: Number of days of hospitalization due to infections [ Time Frame: 12 months ]
  • Therapeutic efficacy: Duration of use of antibiotics for infection (prophylaxis or treatment) [ Time Frame: 12 months ]
  • Levels of specific antibodies (haemophilus influenzae B, streptococcus pneumonia) [ Time Frame: Screening and Routine IgG, Weeks 1, 10, 13, 21, 61 and 65 ]
  • Quality of Life [ Time Frame: Weeks 1 and 61 ]
    Quality of Life (QoL) will be assessed using Short Form-36 version 2 (SF-36v2) in subjects > 18 years of age
  • Adverse events: Number and percent of infusions associated with one or more AEs that begin during the infusion or within 72 hours after completion of the infusion [ Time Frame: Up to 64 weeks ]
  • Adverse events: Nature, severity, and frequency of AEs (tolerability) [ Time Frame: Up to 68 weeks ]
  • Adverse events: Number of suspected unexpected serious adverse reactions (SUSARs) [ Time Frame: Up to 68 weeks ]
  • Vital signs [ Time Frame: Screening and Routine IgG, Weeks 1, 2, 3, 4, 10, 11, 13, 17, 21, 26, 27, 31,, 36, 41, 46, 61, and 65 ]
    Clinically significant changes in vital signs will be classified as adverse events
  • Laboratory testing [ Time Frame: Screening and Routine IgG, Weeks 1, 4, 13, 17, 21, 61 and 65 ]
    Clinically significant changes in laboratory tests, hematology, clinical chemistry and Direct Coombs' Test
  • Assessment of viral safety [ Time Frame: Weeks 1, 2, 61, and 65 ]
    Tests for HBV, HCV, HIV, and Parvovirus B19
  • Physical examination [ Time Frame: Screening and Routine IgG, Weeks 1-4, 10, 13, 26, 61 and 65 ]
    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 1 and 4 ]
    Haptoglobin and urine hemosiderin


Information By: Bio Products Laboratory

Dates:
Date Received: June 14, 2013
Date Started: August 2015
Date Completion: May 2017
Last Updated: January 3, 2017
Last Verified: January 2017