Titre officiel
A Pilot Trial To Assess The Feasibility And Efficacy Of Subcutaneous Immunoglobulin In Patients With Myasthenia Gravis Exacerbation
Sommaire:
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.
Description de l'essai
Primary Outcome:
- Change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to day 42 after treatment.
Secondary Outcome:
- Quality of life will be assessed through the Quality of Life (QOL) score, a qualitative questionnaire.
- Change in Manual Muscle Testing (MMT) score from baseline to day 42 after treatment.
- Adverse events related to SCIG infusions will be recorded if/when they occur.
- Patient satisfaction with the treatment modality will be assessed using a questionnaire.
- Serious Adverse Events related to SCIG infusions will be recorded if/when they occur.
- Proportion of participants successfully trained will be recorded indicating feasibility based on patient compliance.
- Proportion of participants completing will be recorded indicating feasibility based on patient compliance.
- Myasthenia
Gravis (MG) Composite scores will be used to evaluate disease severity
through a number of functional assessments, including muscle strength
and ability to complete activities of daily living.
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.
Voir cet essai sur ClinicalTrials.gov
