Myasthenia GravisPhase 3SCIG-MGNCT02774239
A Pilot Trial To Assess The Feasibility And Efficacy Of SCIG In Patients With MG Exacerbation (SCIG-MG)
A Phase 3 study testing Human normal immunoglobulin G (IgG) in people with Myasthenia Gravis, run by University of Alberta at 2 sites in Canada.
Trial summary
This is a prospective open-label, uncontrolled, single-blind, pilot clinical trial. The primary objective is to assess the efficacy, safety, feasibility and tolerability of SCIG in patients with worsening MG. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Myasthenia Gravis
- What is being tested?
- Human normal immunoglobulin G (IgG)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesCanada
- Study dates
- Oct 2014to 21 Oct 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients between18 to 80 years of age, diagnosed with MG (see below) who have worsening myasthenic symptoms - (defined as increasing diplopia, ptosis, dysarthria, dysphagia, difficulty chewing, or limb weakness severe enough to warrant immunoglobulin therapy.
- MG diagnosis will be based upon the clinical evaluation by a neuromuscular expert and meeting any two of the following supportive criteria:
- Abnormal Tensilon test
- Abnormal repetitive nerve stimulation studies
- Abnormal single fiber electromyography (EMG)
- Increased serum acetylcholine receptor or anti-MuSK antibodies
- Prior response to immunotherapy
Who cannot join
- Respiratory distress requiring ICU admission or a vital capacity <1 L
- Severe swallowing difficulties with a high risk of aspiration
- Change in corticosteroid dosage in the 4 weeks prior to screening
- Known immunoglobulin A (IgA) deficiency
- Pregnant or breast feeding women
- Active renal or hepatic insufficiency, clinically significant cardiac disease
Show all 9Show fewer
- Patients with worsening weakness associated with an infectious process
- Previous lack of responsiveness to IVIG
- History of previous MG crises
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
University of Alberta
Edmonton, Alberta, T6G 2B7
Vancouver General Hospital - Gordon & Leslie Diamond Health Care Centre
Vancouver, British Columbia, V5Z 1M9
About this study
Official title: A Pilot Trial To Assess The Feasibility And Efficacy Of Subcutaneous Immunoglobulin In Patients With Myasthenia Gravis Exacerbation
This is a prospective open-label, uncontrolled, single-blind, pilot clinical trial.
The primary objective is to assess the efficacy, safety, feasibility and tolerability of SCIG in patients with worsening MG.
Read more
Participants with moderate worsening of MG symptoms (MGFA Class II and III) who are considered to be appropriate for immunoglobulin therapy will be screened for the study by the treating neurologist.
Patients will be receive 2gm/kg (150gm for a 75kg patient) of 20% SCIG (Hizentra) infused over 4 weeks in a dose escalating manner.
Additionally, this study will be assessing the feasibility of employing SCIG as an alternative therapy to IVIG in patients with MG exacerbation. The cost-effectiveness of SCIG versus IVIG will be evaluated, and the impact of SCIG therapy will be assessed from both a health-resource perspective and from a patient perspective.
Read the detailed description
This is a prospective open-label, uncontrolled, single-blind, pilot clinical trial.
The primary objective is to assess the efficacy, safety, feasibility and tolerability of SCIG in patients with worsening MG.
Study Rationale and Significance
Subcutaneous immunoglobulin (SCIG) is a novel form of immune therapy for neuromuscular diseases and may offer several advantages over intravenous immunoglobulin (IVIG).
Although no large-scale studies have been in conducted in MG patients, pilot studies with SCIG in multifocal motor neuropathy indicate that it may be a feasible, effective and safe alternative to IVIG in a condition, which like MG, shows excellent response to IVIG infusion.
Patients are able to tolerate it better and have improved quality of life due to added flexibility to the treatment schedule. SCIG is also potentially less expensive than IVIG since the costs associated with inpatient treatment as well as nursing support are saved.
SCIG also has the potential to be more effective and durable since the serum levels of immunoglobulin show a more sustained increase compared to IVIG. A drawback associated with SCIG is the small amount of immunoglobulin that can be infused over a short period. As compared to IVIG where the usual dose (2gm/kg for neuromuscular diseases) can be infused over 2 - 5 days, the same dose of SCIG would require 3 - 4 weeks to be administered with the currently available formulations. This may mean a delayed onset of peak-dose effect and SCIG may not be feasible for MG patients who are rapidly worsening or in MG crisis.
Nevertheless, SCIG may be an attractive option in a large subpopulation of MG patients who have mild to moderate disease exacerbations or who are on maintenance IVIG therapy provided its efficacy, tolerability and feasibility is determined in this patient population.
Methodology
Participants with moderate worsening of MG symptoms (MGFA Class II and III) who are considered to be appropriate for immunoglobulin therapy at the MG clinic at the University of Alberta will be screened for the study by the treating neurologist.
Patients will be receive 2gm/kg (150gm for a 75kg patient) of 20% SCIG (Hizentra) infused over 4 weeks in a dose escalating manner. Participants will undergo infusions two to four times a week, depending on their tolerance, beginning with a dose of 10 ml per site at four injection sites, increasing by 5 ml per week for a total of 25 ml per site at four injection sites after four weeks.
The dose is flexible and will vary based on the patient's tolerance to the medication and the total amount of medication the patient will be receiving based on their body weight. The initial (one or two) doses will be infused within the medical outpatient facility at the University of Alberta Hospital. This will allow for the observation of any infusion reactions and will also serve as nurse-provided self- infusion training sessions for patients.
Participants will be assessed weekly for symptomatic change and reports of satisfaction and quality of life. The primary outcome variable is the change in the Quantitative Myasthenia Gravis (QMG) Score for Disease Severity from baseline to day 42 (6 weeks). A change of 3.5 points will be considered to be clinically significant.
Safety and pharmacokinetic assessments of SCIG will be performed weekly throughout the study.
Additionally, this study will be assessing the feasibility of employing SCIG as an alternative therapy to IVIG in patients with MG exacerbation. The cost-effectiveness of SCIG versus IVIG will be evaluated, and the impact of SCIG therapy will be assessed from both a health-resource perspective and from a patient perspective.
The practicality of using SCIG in patients with MG will be determined by documenting the number of patients who are able to be trained for self- administration of SCIG, and by the patients' self-reported satisfaction with SCIG treatment.
The speed of SCIG treatment onset will also be assessed and compared to IVIG treatment onset. All of these described measures will be used to determine the feasibility and practicality of using SCIG in patients with MG exacerbation and its impact on the healthcare system.
- Conditions
- Myasthenia Gravis
- Being tested
- Human normal immunoglobulin G (IgG)
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human normal immunoglobulin G (IgG)Drug
Also called Hizentra®
Study medication is available in the following forms: 5 mL (1 g IgG) in a 5 mL infusion bottle, 10 mL (2 g IgG) in a 10 mL infusion bottle, 20 mL (4 g IgG) in a 20 mL infusion bottle, 50 mL (10 g IgG) in a 50 mL infusion bottle.
Patients will be receiving 2gm/kg (150gm for a 75kg patient) of 20% SCIG (Hizentra) infused over four weeks in a dose escalating manner.
| Study group | Role | What they receive |
|---|---|---|
| SC Treatment Period | Experimental | Participants will receive 2gm/kg of Human normal immunoglobulin G (IgG) infused over 4 weeks in a dose escalating manner as follows:
* 1st week: 2-3 SCIG infusions of 10ml per site at four sites (total dose 16 to 24g)*
* 2nd week: 2-3 SCIG infusions of 15ml per site at four sites (total dose 24 to 36g)*
* 3rd week: 2-4 SCIG infusions of 20ml per site at four sites (total dose 32 to 64g)*
* 4th week: 2-4 SCIG infusions of 25ml per site at four sites (total dose 40 to 80g)*
* Doses indicated are study recommended. Doses may be adjusted depending on tolerance and total dose required by the patient. Receives: Drug: Human normal immunoglobulin G (IgG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to day 42 after treatment.
QMGS is a validated clinical measure of myasthenia gravis ranging from 0 points (no myasthenic weakness) to a maximum of 39 points, with a defined change of 3.4 units required for clinical significance.
Measured: Baseline - Day 42
Secondary outcomes (8)
Quality of life will be assessed through the Quality of Life (QOL) score, a qualitative questionnaire.
Measured: Baseline - Day 42
Change in Manual Muscle Testing (MMT) score from baseline to day 42 after treatment.
MMT is a validated clinical measure of myasthenia gravis ranging from 0 points (no myasthenic weakness) to a maximum of 128 points, with a defined change of 25% from baseline required for clinical significance.
Measured: Baseline - Day 42
Adverse events related to SCIG infusions will be recorded if/when they occur.
Measured: Baseline - Day 42
Patient satisfaction with the treatment modality will be assessed using a questionnaire.
TQSM: Treatment Satisfaction Questionnaire for Medication. An 11 question ordinal scale measuring responses from "Extremely satisfied" to "Extremely dissatisfied" over a 7 item option list. Questions cover four domains, corresponding to distinct aspects related to the satisfaction of patients with their treatment (Effectiveness; Side effects; Convenience and Global satisfaction). A score can be obtained for each domain by summing of the corresponding items transformed on a 0-100 scale; higher values indicate higher satisfaction, better perceived effectiveness, lower burden associated to side-effects, better convenience
Measured: Day 42
Serious Adverse Events related to SCIG infusions will be recorded if/when they occur.
Measured: Baseline - Day 42
Proportion of participants successfully trained will be recorded indicating feasibility based on patient compliance.
Measured: Baseline - Week 2
Proportion of participants completing will be recorded indicating feasibility based on patient compliance.
Measured: Baseline - Day 42
Myasthenia Gravis (MG) Composite scores will be used to evaluate disease severity through a number of functional assessments, including muscle strength and ability to complete activities of daily living.
Measured: Baseline - Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2016 (estimated)
- Study startOct 2014
- Primary completion21 Oct 2022
- Study completion21 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myasthenia GravisStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- CSL Behring
- Responsible party
- Sponsor
- Investigators
- Zaeem A Siddiqi, MD, PhD, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02774239
- Sponsor's protocol ID
- ZS2013-01
- Acronym
- SCIG-MG
- Status last verified
- Feb 2023
- First submitted
- 20 Apr 2015
- Last updated
- 21 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial To Assess The Feasibility And Efficacy Of Subcutaneous Immunoglobulin In Patients With Myasthenia Gravis Exacerbation
- ClinicalTrials.gov ID
- NCT02774239
- Acronym / sponsor ID
- SCIG-MG / ZS2013-01
- Conditions
- Myasthenia Gravis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Collaborators
- CSL Behring
- Study start
- Oct 2014
- Primary completion
- 21 Oct 2022 (actual)
- Study completion
- 21 Oct 2022 (actual)
- First posted
- 17 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective open-label, uncontrolled, single-blind, pilot clinical trial.
The primary objective is to assess the efficacy, safety, feasibility and tolerability of SCIG in patients with worsening MG.
Participants with moderate worsening of MG symptoms (MGFA Class II and III) who are considered to be appropriate for immunoglobulin therapy will be screened for the study by the treating neurologist.
Patients will be receive 2gm/kg (150gm for a 75kg patient) of 20% SCIG (Hizentra) infused over 4 weeks in a dose escalating manner.
Additionally, this study will be assessing the feasibility of employing SCIG as an alternative therapy to IVIG in patients with MG exacerbation. The cost-effectiveness of SCIG versus IVIG will be evaluated, and the impact of SCIG therapy will be assessed from both a health-resource perspective and from a patient perspective.
Detailed description
This is a prospective open-label, uncontrolled, single-blind, pilot clinical trial.
The primary objective is to assess the efficacy, safety, feasibility and tolerability of SCIG in patients with worsening MG.
Study Rationale and Significance
Subcutaneous immunoglobulin (SCIG) is a novel form of immune therapy for neuromuscular diseases and may offer several advantages over intravenous immunoglobulin (IVIG).
Although no large-scale studies have been in conducted in MG patients, pilot studies with SCIG in multifocal motor neuropathy indicate that it may be a feasible, effective and safe alternative to IVIG in a condition, which like MG, shows excellent response to IVIG infusion.
Patients are able to tolerate it better and have improved quality of life due to added flexibility to the treatment schedule. SCIG is also potentially less expensive than IVIG since the costs associated with inpatient treatment as well as nursing support are saved.
SCIG also has the potential to be more effective and durable since the serum levels of immunoglobulin show a more sustained increase compared to IVIG. A drawback associated with SCIG is the small amount of immunoglobulin that can be infused over a short period. As compared to IVIG where the usual dose (2gm/kg for neuromuscular diseases) can be infused over 2 - 5 days, the same dose of SCIG would require 3 - 4 weeks to be administered with the currently available formulations. This may mean a delayed onset of peak-dose effect and SCIG may not be feasible for MG patients who are rapidly worsening or in MG crisis.
Nevertheless, SCIG may be an attractive option in a large subpopulation of MG patients who have mild to moderate disease exacerbations or who are on maintenance IVIG therapy provided its efficacy, tolerability and feasibility is determined in this patient population.
Methodology
Participants with moderate worsening of MG symptoms (MGFA Class II and III) who are considered to be appropriate for immunoglobulin therapy at the MG clinic at the University of Alberta will be screened for the study by the treating neurologist.
Patients will be receive 2gm/kg (150gm for a 75kg patient) of 20% SCIG (Hizentra) infused over 4 weeks in a dose escalating manner. Participants will undergo infusions two to four times a week, depending on their tolerance, beginning with a dose of 10 ml per site at four injection sites, increasing by 5 ml per week for a total of 25 ml per site at four injection sites after four weeks.
The dose is flexible and will vary based on the patient's tolerance to the medication and the total amount of medication the patient will be receiving based on their body weight. The initial (one or two) doses will be infused within the medical outpatient facility at the University of Alberta Hospital. This will allow for the observation of any infusion reactions and will also serve as nurse-provided self- infusion training sessions for patients.
Participants will be assessed weekly for symptomatic change and reports of satisfaction and quality of life. The primary outcome variable is the change in the Quantitative Myasthenia Gravis (QMG) Score for Disease Severity from baseline to day 42 (6 weeks). A change of 3.5 points will be considered to be clinically significant.
Safety and pharmacokinetic assessments of SCIG will be performed weekly throughout the study.
Additionally, this study will be assessing the feasibility of employing SCIG as an alternative therapy to IVIG in patients with MG exacerbation. The cost-effectiveness of SCIG versus IVIG will be evaluated, and the impact of SCIG therapy will be assessed from both a health-resource perspective and from a patient perspective.
The practicality of using SCIG in patients with MG will be determined by documenting the number of patients who are able to be trained for self- administration of SCIG, and by the patients' self-reported satisfaction with SCIG treatment.
The speed of SCIG treatment onset will also be assessed and compared to IVIG treatment onset. All of these described measures will be used to determine the feasibility and practicality of using SCIG in patients with MG exacerbation and its impact on the healthcare system.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SC Treatment Period | Experimental | Drug: Human normal immunoglobulin G (IgG)Participants will receive 2gm/kg of Human normal immunoglobulin G (IgG) infused over 4 weeks in a dose escalating manner as follows: * 1st week: 2-3 SCIG infusions of 10ml per site at four sites (total dose 16 to 24g)* * 2nd week: 2-3 SCIG infusions of 15ml per site at four sites (total dose 24 to 36g)* * 3rd week: 2-4 SCIG infusions of 20ml per site at four sites (total dose 32 to 64g)* * 4th week: 2-4 SCIG infusions of 25ml per site at four sites (total dose 40 to 80g)* * Doses indicated are study recommended. Doses may be adjusted depending on tolerance and total dose required by the patient. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients between18 to 80 years of age, diagnosed with MG (see below) who have worsening myasthenic symptoms - (defined as increasing diplopia, ptosis, dysarthria, dysphagia, difficulty chewing, or limb weakness severe enough to warrant immunoglobulin therapy.
- MG diagnosis will be based upon the clinical evaluation by a neuromuscular expert and meeting any two of the following supportive criteria:
Key exclusion criteria (9 listed)
- Respiratory distress requiring ICU admission or a vital capacity <1 L
- Severe swallowing difficulties with a high risk of aspiration
- Change in corticosteroid dosage in the 4 weeks prior to screening
- Known immunoglobulin A (IgA) deficiency
- Pregnant or breast feeding women
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 |
|---|---|---|
| Human normal immunoglobulin G (IgG)Also: Hizentra®Study medication is available in the following forms: 5 mL (1 g IgG) in a 5 mL infusion bottle, 10 mL (2 g IgG) in a 10 mL infusion bottle, 20 mL (4 g IgG) in a 20 mL infusion bottle, 50 mL (10 g IgG) in a 50 mL infusion bottle. Patients will be receiving 2gm/kg (150gm for a 75kg patient) of 20% SCIG (Hizentra) infused over four weeks in a dose escalating manner. | Drug | SC Treatment Period |
Primary outcome
Change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to day 42 after treatment.
Time frame: Baseline - Day 42
QMGS is a validated clinical measure of myasthenia gravis ranging from 0 points (no myasthenic weakness) to a maximum of 39 points, with a defined change of 3.4 units required for clinical significance.
8 secondary outcomes
Quality of life will be assessed through the Quality of Life (QOL) score, a qualitative questionnaire.
Time frame: Baseline - Day 42
Change in Manual Muscle Testing (MMT) score from baseline to day 42 after treatment.
Time frame: Baseline - Day 42
Adverse events related to SCIG infusions will be recorded if/when they occur.
Time frame: Baseline - Day 42
Patient satisfaction with the treatment modality will be assessed using a questionnaire.
Time frame: Day 42
Serious Adverse Events related to SCIG infusions will be recorded if/when they occur.
Time frame: Baseline - Day 42
Proportion of participants successfully trained will be recorded indicating feasibility based on patient compliance.
Time frame: Baseline - Week 2
Proportion of participants completing will be recorded indicating feasibility based on patient compliance.
Time frame: Baseline - Day 42
Myasthenia Gravis (MG) Composite scores will be used to evaluate disease severity through a number of functional assessments, including muscle strength and ability to complete activities of daily living.
Time frame: Baseline - Day 42
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
- Individual participant dataSharing planned: No
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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.
Zaeem A Siddiqi, MD, PhD principal investigator
University of Alberta
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Human normal immunoglobulin G (IgG) in people with Myasthenia Gravis, run by University of Alberta at 2 sites in Canada.
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 7 inclusion and 9 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 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in Quantitative Myasthenia Gravis Score (QMGS) from baseline to day 42 after treatment. (time frame: Baseline - Day 42). 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 21 Feb 2023.