A Pilot Trial To Assess The Feasibility And Efficacy Of SCIG In Patients With MG Exacerbation (SCIG-MG)
Condition: Myasthenia Gravis
MeSH terms: Myasthenia Gravis
Study type: Interventional
Phase: Phase 3

Summary: 
      This is a prospective open-label, uncontrolled, single-blind, pilot clinical trial.

      The primary objective is to assess the efficacy, safety, feasibility and tolerability of SCIG
      in patients with worsening MG.

      Participants with moderate worsening of MG symptoms (MGFA Class II and III) who are
      considered to be appropriate for immunoglobulin therapy will be screened for the study by the
      treating neurologist.

      Patients will be receive 2gm/kg (150gm for a 75kg patient) of 20% SCIG (Hizentra) infused
      over 4 weeks in a dose escalating manner.

      Additionally, this study will be assessing the feasibility of employing SCIG as an
      alternative therapy to IVIG in patients with MG exacerbation. The cost-effectiveness of SCIG
      versus IVIG will be evaluated, and the impact of SCIG therapy will be assessed from both a
      health-resource perspective and from a patient perspective.
    

Detailed description: 
      This is a prospective open-label, uncontrolled, single-blind, pilot clinical trial.

      The primary objective is to assess the efficacy, safety, feasibility and tolerability of SCIG
      in patients with worsening MG.

      Study Rationale and Significance

      Subcutaneous immunoglobulin (SCIG) is a novel form of immune therapy for neuromuscular
      diseases and may offer several advantages over intravenous immunoglobulin (IVIG).

      Although no large-scale studies have been in conducted in MG patients, pilot studies with
      SCIG in multifocal motor neuropathy indicate that it may be a feasible, effective and safe
      alternative to IVIG in a condition, which like MG, shows excellent response to IVIG infusion.

      Patients are able to tolerate it better and have improved quality of life due to added
      flexibility to the treatment schedule. SCIG is also potentially less expensive than IVIG
      since the costs associated with inpatient treatment as well as nursing support are saved.

      SCIG also has the potential to be more effective and durable since the serum levels of
      immunoglobulin show a more sustained increase compared to IVIG. A drawback associated with
      SCIG is the small amount of immunoglobulin that can be infused over a short period. As
      compared to IVIG where the usual dose (2gm/kg for neuromuscular diseases) can be infused over
      2 - 5 days, the same dose of SCIG would require 3 - 4 weeks to be administered with the
      currently available formulations. This may mean a delayed onset of peak-dose effect and SCIG
      may not be feasible for MG patients who are rapidly worsening or in MG crisis.

      Nevertheless, SCIG may be an attractive option in a large subpopulation of MG patients who
      have mild to moderate disease exacerbations or who are on maintenance IVIG therapy provided
      its efficacy, tolerability and feasibility is determined in this patient population.

      Methodology

      Participants with moderate worsening of MG symptoms (MGFA Class II and III) who are
      considered to be appropriate for immunoglobulin therapy at the MG clinic at the University of
      Alberta will be screened for the study by the treating neurologist.

      Patients will be receive 2gm/kg (150gm for a 75kg patient) of 20% SCIG (Hizentra) infused
      over 4 weeks in a dose escalating manner. Participants will undergo infusions two to four
      times a week, depending on their tolerance, beginning with a dose of 10 ml per site at four
      injection sites, increasing by 5 ml per week for a total of 25 ml per site at four injection
      sites after four weeks.

      The dose is flexible and will vary based on the patient's tolerance to the medication and the
      total amount of medication the patient will be receiving based on their body weight. The
      initial (one or two) doses will be infused within the medical outpatient facility at the
      University of Alberta Hospital. This will allow for the observation of any infusion reactions
      and will also serve as nurse-provided self- infusion training sessions for patients.

      Participants will be assessed weekly for symptomatic change and reports of satisfaction and
      quality of life. The primary outcome variable is the change in the Quantitative Myasthenia
      Gravis (QMG) Score for Disease Severity from baseline to day 42 (6 weeks). A change of 3.5
      points will be considered to be clinically significant.

      Safety and pharmacokinetic assessments of SCIG will be performed weekly throughout the study.

      Additionally, this study will be assessing the feasibility of employing SCIG as an
      alternative therapy to IVIG in patients with MG exacerbation. The cost-effectiveness of SCIG
      versus IVIG will be evaluated, and the impact of SCIG therapy will be assessed from both a
      health-resource perspective and from a patient perspective.

      The practicality of using SCIG in patients with MG will be determined by documenting the
      number of patients who are able to be trained for self- administration of SCIG, and by the
      patients' self-reported satisfaction with SCIG treatment.

      The speed of SCIG treatment onset will also be assessed and compared to IVIG treatment onset.
      All of these described measures will be used to determine the feasibility and practicality of
      using SCIG in patients with MG exacerbation and its impact on the healthcare system.
    

Intervention name(s): Human normal immunoglobulin G (IgG)
Intervention type(s): Drug
Intervention description(s): Study medication is available in the following forms: 5 mL (1 g IgG) in a 5 mL infusion bottle, 10 mL (2 g IgG) in a 10 mL infusion bottle, 20 mL (4 g IgG) in a 20 mL infusion bottle, 50 mL (10 g IgG) in a 50 mL infusion bottle.
Patients will be receiving 2gm/kg (150gm for a 75kg patient) of 20% SCIG (Hizentra) infused over four weeks in a dose escalating manner.
Other intervention name(s): Hizentra®
Intervention MeSH terms: Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; Immunoglobulin G
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment