Myasthenia GravisPhase 2NCT02100969
Open Label Study of Subcutaneous Immunoglobulin (SCIg) in Myasthenia Gravis
A Phase 2 study testing HIZENTRA ® in people with Myasthenia Gravis, run by Mazen Dimachkie, MD at 5 sites in 2 countries.
Trial summary
The purpose of this study is to determine whether Hizentra is a safe and effective treatment for people with myasthenia gravis (MG). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myasthenia Gravis
- What is being tested?
- HIZENTRA ®
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 5 sitesin 2 countries
- Study dates
- May 2015to Jan 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
United States4 sites
University at Buffalo
Buffalo, New York, 14203
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
University of Kansas Medical Center
Kansas City, Kansas, 66160
Phoenix Neurological Associates
Phoenix, Arizona, 85018
About this study
The purpose of this study is to determine whether Hizentra is a safe and effective treatment for people with myasthenia gravis (MG).
Read the 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.
- Conditions
- Myasthenia Gravis
- Being tested
- HIZENTRA ®
- Keywords
- MG, Hizentra, autoimmune neuromuscular disorder
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HIZENTRA ®Drug
Also called Immune Globulin Subcutaneous (Human), 20% Liquid
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: HIZENTRA ® |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from Baseline to Week 12
Secondary outcomes (8)
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.
Measured: Change from Baseline to Week 12
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.
Measured: Change from Baseline to Week 12
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.
Measured: Change from Baseline to Week 12
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.
Measured: Change from Baseline to Week 12
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.
Measured: Change from Baseline to Week 12
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.
Measured: Change from Baseline to Week 12
Immunoglobulin G (IgG) Antibody Levels
Measure IgG level (mg/dL) between intravenous and subcutaneous study phases. Normal range equals 762-1488 mg/dL.
Measured: Change from "Week -10 to Week 0" versus "Week 1 to Week 12"
Tolerabililty
Tolerability is assessed as the number of subjects who completed the study and/or did not withdraw due to worsening.
Measured: 12 weeks from start of SCIg
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2014 (estimated)
- Study startMay 2015
- Primary completionNov 2017
- Study completionJan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myasthenia GravisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mazen Dimachkie, MD
- Sponsor type
- University, hospital or other
- Collaborators
- CSL Behring
- Responsible party
- Sponsor-investigator, Mazen Dimachkie, MD, University of Kansas Medical Center
- Investigators
- Mazen M Dimachkie, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02100969
- Sponsor's protocol ID
- STUDY00001041
- Status last verified
- May 2021
- First submitted
- 27 Mar 2014
- Last updated
- 2 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Study of Subcutaneous Immunoglobulin (SCIg) in Myasthenia Gravis
- ClinicalTrials.gov ID
- NCT02100969
- Acronym / sponsor ID
- STUDY00001041
- Conditions
- Myasthenia Gravis
- Keywords
- MG, Hizentra, autoimmune neuromuscular disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Mazen Dimachkie, MDUniversity, hospital or other
- Collaborators
- CSL Behring
- Study start
- May 2015 (actual)
- Primary completion
- Nov 2017 (actual)
- Study completion
- Jan 2018 (actual)
- First posted
- 1 Apr 2014 (estimated)
- Results
- Posted 13 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HIZENTRA ® | Experimental | Drug: HIZENTRA ®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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HIZENTRA ®Also: Immune Globulin Subcutaneous (Human), 20% LiquidPatients 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. | Drug | HIZENTRA ® |
Primary outcome
Proportion of Patients Whose Quantitative Myasthenia Gravis Scores Are Increased by no More Than 3 Points at the End of the SCIg Treatment Phase
Time frame: Change from Baseline to Week 12
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.
8 secondary outcomes
Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) Scores
Time frame: Change from Baseline to Week 12
Myasthenia Gravis Quality of Life (MG QOL-15) Scores
Time frame: Change from Baseline to Week 12
Myasthenia Gravis Composite (MGC) Score
Time frame: Change from Baseline to Week 12
Treatment Satisfaction Questionnaire for Medication (TSQM) - Convenience Score
Time frame: Change from Baseline to Week 12
Treatment Satisfaction Questionnaire for Medication (TSQM) - Effectiveness Score
Time frame: Change from Baseline to Week 12
Treatment Satisfaction Questionnaire for Medication (TSQM) - Satisfaction Score
Time frame: Change from Baseline to Week 12
Immunoglobulin G (IgG) Antibody Levels
Time frame: Change from "Week -10 to Week 0" versus "Week 1 to Week 12"
Tolerabililty
Time frame: 12 weeks from start of SCIg
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mazen M Dimachkie, MD principal investigator
University of Kansas Medical Center
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HIZENTRA ® in people with Myasthenia Gravis, run by Mazen Dimachkie, MD at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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 (time frame: Change from Baseline to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2021.