Open Label Study of Subcutaneous Immunoglobulin (SCIg) in Myasthenia Gravis

Myasthenia Gravis Clinical Trial

Official title:

Open Label Study of Subcutaneous Immunoglobulin (SCIg) in Myasthenia Gravis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02100969
• Other study ID #: STUDY00001041
• Status: Completed
• Phase: Phase 2
• Start date: May 2015
• Est. completion date: January 2018

Study information

• Verified date: May 2021
• Source: University of Kansas Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether Hizentra is a safe and effective treatment for people with myasthenia gravis (MG).

Description:

Myasthenia gravis (MG) is a rare autoimmune disorder which causes the muscles to become weak because the immune system attacks the connection between the nerves and the muscles. Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). An immunoglobin is a blood protein. Hizentra is being studied for the treatment of patients with MG. Hizentra is administered by an injection into the skin through a portable infusion pump, which may be easier for patients to administer than the current treatments. Participants will be asked to complete 9 clinic visits and 3 telephone calls. It could take up to 30 weeks to complete all study visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: January 2018
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients 18 and older
• Patients must have prior or current documentation of MGFA MG grades 2, 3, or 4 generalized MG, according to the MGFA classification system.48 These grades correspond to mild (2), moderate (3), and severe (4)
• Elevated AChR or MuSK Ab. These tests will have been performed at some time prior to entry into the study. Double seronegative MG patients with prior documentation of an abnormal decrement (>10%) on slow repetitive nerve stimulation or an abnormal single fiber EMG will also be allowed to participate
• Patient's signs and symptoms should not be better explained by another disease process.
• IVIg maintenance dose of 0.2 to 2 gm/kg/4 weeks or equivalent dose administered Q 2-4 weeks±3days
• Stable IVIg for at least 3 cycles (definition of stability: no change in prescribed dosage or frequency by the treating physician)
• Patient must be receiving no more than 200g/4weeks of IVIg.
• Patients must be willing to complete the study and return for follow-up visits.
• Patients must be willing to give written informed consent before participating in this study. A copy of the signed consent must be kept in the patient's medical record.
• Patients can be on the following drugs as long as there has been no dose change for 60 days: azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, tacrolimus, methotrexate or other immunosuppressive drugs.
• Patients can be on prednisone as long as there has been no dose change for 30 days.

Exclusion Criteria:

• MGFA grade V within 6 months of screening.
• A history of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue.
• Other major chronic or debilitating illnesses within six months prior to study entry.
• Female patients who are premenopausal and are: (a) pregnant on the basis of a serum pregnancy test, (b) breast-feeding, or (c) not using an effective method of double barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures).
• Altered levels of consciousness, dementia, or abnormal mental status.
• Thymectomy in the previous three months.
• Evidence of renal insufficiency (Cr>1.5 x elevated) or liver disease (transaminases > 2.5 x elevation) at screening.
• Skin disease that would interfere with assessment of injection site reaction
• History of severe reactions to IVIg or SCIg.
• Participation in a research study within the last 3 months
• Treatment with rituximab or other biologics within 12 months of study entry
• Inability to provide informed consent.
• History of thrombotic episodes within the last year prior to enrollment
• Known allergic or other severe reactions to blood products including intolerability to previous normal human immunoglobulin for intravenous administration (IVIG) and/or subcutaneous immunoglobulin (SCIG), such as history of clinically relevant hemolysis after IVIG infusion, aseptic meningitis, recurrent severe headache, hypersensitivity, severe generalized or severe local skin reaction.
• History of IgA deficiency or evidence of IgA deficiency at screening.

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis

Intervention

Drug:
• HIZENTRA ®
Patients must fulfill inclusion criteria and remain stable at week 0, which means QMG does not increase by 3 points, will enter receive Hizentra for 12 weeks.

Locations

Country	Name	City	State
Canada	University of Toronto	Toronto	Ontario
United States	University at Buffalo	Buffalo	New York
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Phoenix Neurological Associates	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Mazen Dimachkie, MD	CSL Behring

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients Whose Quantitative Myasthenia Gravis Scores Are Increased by no More Than 3 Points at the End of the SCIg Treatment Phase	The QMG is a 13 item ordinal scale which measures ocular, bulbar, extremity fatigue and strength, along with respiratory function. The scale is from 0 - 3 for each item, with 0 meaning normal and 3 is severe. Total score can range from 0 to 39.; Change in MG severity will be measured using the Quantitative Myasthenia Gravis (QMG) Score for Disease severity. The QMG is a validated clinical composite scale. As mentioned in the protocol, our hypotheses are: H0: Proportion of patients whose QMG scores are increased by more than 3 points at the end of the SCIg treatment phase = 0.65 HA: Proportion of patients whose QMG scores are increased by no more than 3 points at the end of the SCIg treatment phase > 0.65; Thus, analysis of the primary outcome is done as a one-sample Z test of proportions. That is, the QMG is a continuous outcome, but analyses results are reported as proportions.	Change from Baseline to Week 12
Secondary	Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) Scores	Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL): Composite measure of scores from measurement scales. The MG-ADL has a scale of 0 - 24 with 0 being the lowest (no symptoms) and 24 being the highest (most severe symptoms. The MG-ADL is a staff-administered, patient-reported questionnaire that measures 8 commons symptoms of myasthenia gravis and grades them on a scale of 0 - 3.	Change from Baseline to Week 12
Secondary	Myasthenia Gravis Quality of Life (MG QOL-15) Scores	MG Quality of Life (QOL)-15: Composite measure of scores from measurement scales. The MG QOL-15 is a questionnaire answered by the patient that asked about different symptoms of MG. The questionnaire consists of 15 questions that are graded on a scale of 0 - 4. The total score has a range of 0 - 60 with a higher score meaning more severe symptoms or a worse outcome.	Change from Baseline to Week 12
Secondary	Myasthenia Gravis Composite (MGC) Score	The MGC takes scores from the MG-ADL, the QMG, and combines them will manual muscle testing scores to create the MGC. The scale of this score ranges from 0 - 50 with higher scores meaning a worse outcome or more sever symptoms.	Change from Baseline to Week 12
Secondary	Treatment Satisfaction Questionnaire for Medication (TSQM) - Convenience Score	Treatment Satisfaction Questionnaire for Medication (TSQM) - Convenience Score measured on a scale of 0 to 100. 0 indicates no treatment convenience satisfaction and 100 indicates highest treatment convenience satisfaction.	Change from Baseline to Week 12
Secondary	Treatment Satisfaction Questionnaire for Medication (TSQM) - Effectiveness Score	Treatment Satisfaction Questionnaire for Medication (TSQM) - Effectiveness Score measured on a scale of 0 to 100. 0 indicates no treatment effectiveness satisfaction and 100 indicates highest treatment effectiveness satisfaction.	Change from Baseline to Week 12
Secondary	Treatment Satisfaction Questionnaire for Medication (TSQM) - Satisfaction Score	Treatment Satisfaction Questionnaire for Medication (TSQM) - Satisfaction Score measured on a scale of 0 to 100. 0 indicates no treatment satisfaction and 100 indicates highest treatment satisfaction.	Change from Baseline to Week 12
Secondary	Immunoglobulin G (IgG) Antibody Levels	Measure IgG level (mg/dL) between intravenous and subcutaneous study phases. Normal range equals 762-1488 mg/dL.	Change from "Week -10 to Week 0" versus "Week 1 to Week 12"
Secondary	Tolerabililty	Tolerability is assessed as the number of subjects who completed the study and/or did not withdraw due to worsening.	12 weeks from start of SCIg