Clinical trial NCT04728425: Subcutaneous Immunoglobulin for Myasthenia Gravis
Official title: Efficacy and Safety of Subcutaneous Immunoglobulin in Patients With Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myasthenia Gravis
Keywords: myasthenia gravis
IVIG
SCIG
subcutaneous immunoglobulin
intravenous immunoglobulin
MG
neuromuscular junction
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2021-01-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a prospective open-label, randomized, parallel arm clinical trial.

The primary objective of the study is to evaluate the safety and efficacy of Cuvitru 20% subcutaneous immunoglobulin in patients with myasthenia gravis (MG). The secondary objective is to evaluate patient preferences and effects on quality of life when treating MG patients with SCIG. Exploratory objectives are to compare de novo administration starting SCIG directly with those starting with a loading dose of IVIG followed by SCIG administration.

Patients over age 18 with moderate to severe MG with MGFA Class II-IV without contraindications to immunoglobulin will be considered for the study.

All patients will be eligible to enter either arm of the study, Arm 1: 10% Gammagard IVIG followed by 20% Cuvitry SCIG and Arm 2: Cuvitru 20% SCIG alone.

Detailed description: Myasthenia gravis (MG) is an autoimmune neuromuscular condition which can cause fatigable weakness of skeletal muscles including bulbar, ocular, limb, axial and respiratory muscles. Symptoms range from mild, transient double vision and ptosis to severe, life threatening diffuse weakness, and treatments which are immunosuppressive or immunomodulatory have been shown to improve outcome in MG. This includes 10% intravenous immunoglobulin (IVIG), which has previous been shown by our group to improve strength at 2 and 4 weeks in patients with MG. Due to delay in the onset of many immunosuppressives and potential side effects from steroids and other immunosuppressive medications, IVIG is also used in clinical practice as bridging of maintenance therapy until other therapies take effect or the patient stabilizes. In addition, there have been other studies suggesting that 20% subcutaneous immunoglobuin (SCIG) can be helpful to improve strength in patients with MG over a relatively short period of time (6 weeks). Some of these studies are ongoing and are further evaluating the ability of IVIG and SCIG to stabilize or improve strength IVIG in patients with MG, however, there is no current published study evaluating different administration routes of immunoglobulin (IVIG and SCIG) in patients with MG over a longer 6 month follow-up period.

The current study aims to be the first to evaluate 20% Cuvitru SCIG formulation in patients with neuromuscular conditions including MG. The study aim is to evaluate the safety and efficacy of 6 months of 20% SCIG Cuvitru treatment vs three months of 10% IVIG "pre-treatment" followed by 3 months of 20% SCIG Cuvitru treatment. The study will also be the first to use the myasthenia gravis impairment index (MGII) as primary outcome in conjunction with standard MG outcomes.

Eligibility criteria: Inclusion Criteria:

1. Patients over age 18
2. Patients with a confirmed diagnosis of myasthenia gravis based on clinical criteria including fatiguable weakness and supported by either serological (acetylcholine receptor, muscle specific kinase or anti-low-density lipoprotein receptor- related protein 4 antibodies or electrophysiological testing (repetitive nerve stimulation of single fiber electromyography)
3. Myasthenia Gravis Federation of America class II-IV
4. Moderate to severe myasthenia gravis as defined by a quantitative myasthenia gravis score \>10 or generalized myasthenia gravis impairment index score \> 11
5. Patient able to give consent and is able and willing to complete all study procedures and activities

Exclusion Criteria:

1. Patients who are pregnant or breastfeeding
2. Patients not able to complete the study procedures or with an alternate diagnosis
3. Patients with recent thymectomy in the past 6 months
4. Patients receiving another biologic agent such as rituximab, belimubab, cyclophosphamide and eculizumab in the past 6 months prior to study entry
5. No IVIG or subcutaneous immunoglobulin within the past month
6. Patients on prednisone who have had alterations in prednisone dose over the past month prior to study entry
7. Patients will previous known allergy or severe adverse reaction to intravenous or subcutaneous immunoglobulin
8. Evidence of renal insufficiency (Cr\>1.5 x elevated) or liver disease (transaminases \> 2.5 x elevation) at screening.

Primary outcomes:
measure: Myasthenia Gravis Impairment Index Efficacy Outcome
timeFrame: 6 months
Secondary outcomes:
measure: Quantitative Myasthenia Gravis Score Efficacy Outcome
timeFrame: 6 months
measure: Myasthenia Gravis Activities of Daily Living Efficacy Outcome
timeFrame: 6 months
measure: Myasthenia Gravis Composite Efficacy Outcome
timeFrame: 6 months
measure: Myasthenia gravis Quality of Life 15 Score Efficacy Outcome
timeFrame: 6 months
measure: Parallel Arm Comparison
timeFrame: 6 months
measure: Safety and Tolerability: total number of adverse events
timeFrame: 6 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Hans Katzberg, MD
role: PRINCIPAL_INVESTIGATOR
References: