Open Label Study of Subcutaneous Immunoglobulin (SCIg) in... | NCT02100969

NCT02100969

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
CSL Behring	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.	HIZENTRA ®

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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.

Eligibility Module

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.

Name	Affiliation	Role
Mazen M Dimachkie, MD	University of Kansas Medical Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Phoenix Neurological Associates		Phoenix	Arizona	85018	United States
University of Kansas Medical Center

ID	Title	Description
FG000	Privigen/Hizentra	Privigen: 3 rounds of IV privigen was infused every 4 weeks until baseline visit week 0. Hizentra: Hizentra infused sub cutaneously based on weight and subject prescribed dose.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Hizentra	Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
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.	23 patients were enrolled in the study. The protocol mentions that only those subjects who have stable QMG in the screening phase will be considered eligible for analyses. In our case 22 out of 23 patients are eligible for the final analyses.	Posted		Number	95% Confidence Interval	proportion of participants		Change from Baseline to Week 12

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Privigen/Hizentra	Experimental Treatment arm: Privigen/Hizentra assigned to subjects who are stable in the screening phase of the study.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 22, 2016	Nov 15, 2019	Prot_001.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Feb 22, 2019	Oct 18, 2019	SAP_000.pdf

ID	Term
D020361	Paraneoplastic Syndromes, Nervous System
D009423	Nervous System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms

ID	Term
C558471	Hizentra
D005719	gamma-Globulins
D005440	Fluid Therapy

ID	Term
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins