Subcutaneous Immunoglobulin for Myasthenia Gravis (MG_SCIG)

Efficacy and Safety of Subcutaneous Immunoglobulin in Patients With Myasthenia Gravis

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.

Study Overview

• Status: Completed
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Drug: intravenous immunoglobulin + subcutaneous immunoglobulin (SCIG); Drug: subcutaneous immunoglobulin (SCIG)

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 96 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IVIG + SCIG; This group of MG patients will start with 2g/kg of IVIG on month 1, 1 g/kg of IVIG 4 and then 8 weeks later, and within 2 weeks switch to SCIG treatment	Drug: intravenous immunoglobulin + subcutaneous immunoglobulin (SCIG); 10% intravenous immunoglobulin + 20% subcutaneous immunoglobulin; Other Names: Gammanorm + Cuvitru
Active Comparator: SCIG alone; This group of MG patients will start with SCIG alone	Drug: subcutaneous immunoglobulin (SCIG); 20% subcutaneous immunoglobulin; Other Names: Cuvitru

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myasthenia Gravis Impairment Index Efficacy Outcome	Change in the Myasthenia Gravis Impairment Index (score 0-84, with 84 being the maximal score indicating the most severe MG status) at baseline compared to end of study	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative Myasthenia Gravis Score Efficacy Outcome	Change in the Quantitative Myasthenia Gravis Score (score 0-39, with 39 indicating the most severe clinical findings related to MG) at baseline compared to end of study	6 months
Myasthenia Gravis Activities of Daily Living Efficacy Outcome	Change in the MG Activities of Daily Living (score 0-24, with 24 indicating the most severe clinical findings related to MG) at baseline compared to end of study	6 months
Myasthenia Gravis Composite Efficacy Outcome	Change in the Myasthenia Gravis Composite Score (score 0-50, with 50 indicating the most severe clinical findings related to MG) at baseline compared to end of study) at baseline compared to end of study	6 months
Myasthenia gravis Quality of Life 15 Score Efficacy Outcome	Change in the 15-Item Myasthenia Gravis Quality of Life Score (score 0-45, with 45 indicating the most severe clinical findings related to MG) at baseline compared to end of study) at baseline compared to end of study	6 months
Parallel Arm Comparison	All the above outcomes including the myasthenia gravis impairment index, quantitative myasthenia gravis score, myasthenia gravis activities of daily living, myasthenia gravis composite score, myasthenia gravis quality of life 15 score in patients receiving de novo administration starting SCIG directly with those starting with a loading dose of IVIG followed by SCIG administration will be compared.	6 months
Safety and Tolerability: total number of adverse events	o evaluate the adverse event profile of high dose (20% Cuvitru) SCIG in MG and compare this with existing published adverse events of 20% high-dose SCIG in neuromuscular diseases. Specifically the total number of adverse events as defined in Part C, Division 5 of the Health Canada Food and Drug Regulations will be compared to existing published adverse events of 20% SCIG and the total number of adverse events occuring in the IVIG vs SCIG arms will also be compared.	6 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: Hans Katzberg, MD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2020
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: July 14, 2020
• First Submitted That Met QC Criteria: January 24, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: MG; SCIG; IVIG; myasthenia gravis; intravenous immunoglobulin; subcutaneous immunoglobulin; neuromuscular junction
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Manifestations; Pathologic Processes; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis; Immunologic Factors; Physiological Effects of Drugs; Antibodies; Immunoglobulins; Immunoglobulin G; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 19-5378.2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes