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

NCT02100969 | Completed Phase 2 Results DMC

• 1 other identifier: STUDY00001041
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 5

Brief Summary

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

Conditions

Myasthenia Gravis

Keywords

MG; Hizentra; autoimmune neuromuscular disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) Scores

  Change from Baseline to Week 12

• Myasthenia Gravis Quality of Life (MG QOL-15) Scores

  Change from Baseline to Week 12

• Myasthenia Gravis Composite (MGC) Score

  Change from Baseline to Week 12

• Treatment Satisfaction Questionnaire for Medication (TSQM) - Convenience Score

  Change from Baseline to Week 12

• Treatment Satisfaction Questionnaire for Medication (TSQM) - Effectiveness Score

  Change from Baseline to Week 12

Study Arms (1)

HIZENTRA ®

EXPERIMENTAL

Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive Hizentra in a minimum of one infusion per week and a maximum of 4 infusions per week. Dose and rate depend on the visit and how each participant tolerates the drug. Max cc per site is 50 cc per site per hour.

Drug: HIZENTRA ®

Interventions

HIZENTRA ® DRUG

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.

Also known as: Immune Globulin Subcutaneous (Human), 20% Liquid

HIZENTRA ®

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mazen Dimachkie, MD: lead
• CSL Behring: collaborator

Study Sites (5)

Phoenix Neurological Associates

Phoenix, Arizona, 85018, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University at Buffalo

Buffalo, New York, 14203, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Toronto

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Hizentra; gamma-Globulins; Fluid Therapy

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Therapy; Therapeutics

Results Point of Contact

• Title: Dr. Mazen Dimachkie
• Organization: University of Kansas Medical Center

mdimachkie@kumc.edu

913-588-6970

Study Officials

• Mazen M Dimachkie, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 27, 2014
• First Posted: April 1, 2014
• Study Start: May 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: January 1, 2018
• Last Updated: June 2, 2021
• Results First Posted: December 13, 2019

Record last verified: 2021-05

Locations

US (4); CA (1)