Clinical trial NCT02774239: A Pilot Trial To Assess The Feasibility And Efficacy Of SCIG In Patients With MG Exacerbation (SCIG-MG)
Official title: A Pilot Trial To Assess The Feasibility And Efficacy Of Subcutaneous Immunoglobulin In Patients With Myasthenia Gravis Exacerbation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myasthenia Gravis
Lead sponsor: University of Alberta
Sponsor class: OTHER
Collaborators: name: CSL Behring
First posted: 2016-05-17
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Patients between18 to 80 years of age, diagnosed with MG (see below) who have worsening myasthenic symptoms - (defined as increasing diplopia, ptosis, dysarthria, dysphagia, difficulty chewing, or limb weakness severe enough to warrant immunoglobulin therapy.
* MG diagnosis will be based upon the clinical evaluation by a neuromuscular expert and meeting any two of the following supportive criteria:

  1. Abnormal Tensilon test
  2. Abnormal repetitive nerve stimulation studies
  3. Abnormal single fiber electromyography (EMG)
  4. Increased serum acetylcholine receptor or anti-MuSK antibodies
  5. Prior response to immunotherapy

Exclusion Criteria:

1. Respiratory distress requiring ICU admission or a vital capacity \<1 L
2. Severe swallowing difficulties with a high risk of aspiration
3. Change in corticosteroid dosage in the 4 weeks prior to screening
4. Known immunoglobulin A (IgA) deficiency
5. Pregnant or breast feeding women
6. Active renal or hepatic insufficiency, clinically significant cardiac disease
7. Patients with worsening weakness associated with an infectious process
8. Previous lack of responsiveness to IVIG
9. History of previous MG crises

Primary outcomes:
measure: Change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to day 42 after treatment.
timeFrame: Baseline - Day 42
Secondary outcomes:
measure: Quality of life will be assessed through the Quality of Life (QOL) score, a qualitative questionnaire.
timeFrame: Baseline - Day 42
measure: Change in Manual Muscle Testing (MMT) score from baseline to day 42 after treatment.
timeFrame: Baseline - Day 42
measure: Adverse events related to SCIG infusions will be recorded if/when they occur.
timeFrame: Baseline - Day 42
measure: Patient satisfaction with the treatment modality will be assessed using a questionnaire.
timeFrame: Day 42
measure: Serious Adverse Events related to SCIG infusions will be recorded if/when they occur.
timeFrame: Baseline - Day 42
measure: Proportion of participants successfully trained will be recorded indicating feasibility based on patient compliance.
timeFrame: Baseline - Week 2
measure: Proportion of participants completing will be recorded indicating feasibility based on patient compliance.
timeFrame: Baseline - Day 42
measure: 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.
timeFrame: Baseline - Day 42
Other outcomes:
measure: Cost effectiveness of SCIG therapy will be calculated in comparison to standard IVIG therapy. This will indicate health economics.
timeFrame: Baseline - Day 42
measure: Change in QOL 36 score from Baseline to day 42)
timeFrame: Baseline - Day 42
measure: Time required for the treatments.
timeFrame: Baseline - Day 42
measure: Preference for treatments (Treatment Satisfaction Questionnaire for Medication (TSQM).
timeFrame: Day 42
measure: Intent to continue using SCIG if necessary (Via pt. interview)
timeFrame: Day 42
measure: Proportion of participants successfully trained in self-administration of SCIG.
timeFrame: Day 2, Day 3.
measure: Proportion of participants completing the study.
timeFrame: Day 42
measure: Infusion nurse's assessment of this participant population's ability to use this treatment modality (Written impression)
timeFrame: Day 42
measure: Speed of treatment onset of SCIG.
timeFrame: Day 1
measure: Speed of treatment onset of IVIG.
timeFrame: Day 1
Locations:
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver General Hospital - Gordon & Leslie Diamond Health Care Centre
state: British Columbia
Study officials:
affiliation: University of Alberta
name: Zaeem A Siddiqi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: