Clinical trial NCT02100969: Open Label Study of Subcutaneous Immunoglobulin (SCIg) in Myasthenia Gravis
Official title: Open Label Study of Subcutaneous Immunoglobulin (SCIg) in Myasthenia Gravis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myasthenia Gravis
Keywords: MG
Hizentra
autoimmune neuromuscular disorder
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
Collaborators: name: CSL Behring
First posted: 2014-04-01
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Patients Whose Quantitative Myasthenia Gravis Scores Are Increased by no More Than 3 Points at the End of the SCIg Treatment Phase
timeFrame: Change from Baseline to Week 12
Secondary outcomes:
measure: Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) Scores
timeFrame: Change from Baseline to Week 12
measure: Myasthenia Gravis Quality of Life (MG QOL-15) Scores
timeFrame: Change from Baseline to Week 12
measure: Myasthenia Gravis Composite (MGC) Score
timeFrame: Change from Baseline to Week 12
measure: Treatment Satisfaction Questionnaire for Medication (TSQM) - Convenience Score
timeFrame: Change from Baseline to Week 12
measure: Treatment Satisfaction Questionnaire for Medication (TSQM) - Effectiveness Score
timeFrame: Change from Baseline to Week 12
measure: Treatment Satisfaction Questionnaire for Medication (TSQM) - Satisfaction Score
timeFrame: Change from Baseline to Week 12
measure: Immunoglobulin G (IgG) Antibody Levels
timeFrame: Change from "Week -10 to Week 0" versus "Week 1 to Week 12"
measure: Tolerabililty
timeFrame: 12 weeks from start of SCIg
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Neurological Associates
state: Arizona
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Toronto
country: Canada
facility: University of Toronto
state: Ontario
Study officials:
affiliation: University of Kansas Medical Center
name: Mazen M Dimachkie, MD
role: PRINCIPAL_INVESTIGATOR
References: