Myasthenia Gravis CrisisPhase 4NCT06688253
Intravenous Human IgG1 Fc Fragment (Efgartigimod) in Myasthenic Crisis
A Phase 4 study testing IV efgartigimod in people with Myasthenia Gravis Crisis, run by Rambam Health Care Campus at 1 site in Israel.
Trial summary
Efgartigimod in Myasthenic Crisis Background Myasthenia gravis (MG) is a prevalent autoimmune disorder affecting neuromuscular junctions, characterized by weakness in skeletal muscles. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Myasthenia Gravis Crisis
- What is being tested?
- IV efgartigimod
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteIsrael
- Study dates
- 15 Nov 2024to 30 Mar 2025
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -Age > 18
- MG diagnosis
- A confirmed diagnosis of Myasthenia Gravis (MG) with generalized muscle weakness, classified as MGFA class II, III, IVa, or IVb and V.
- Positive AchR or MuSK antibodies (max three patients of the total cohort) this will be tested in our center for all patients.
- Myasthenic crisis: Worsening of > 3 or an increase >1 MG-ADL points of a sub score of any individual MG-ADL item other than double vision or eyelid droop and its clinically significant by the investigator. Alternatively, weakness related to MG that is severe enough to necessitate intubation or delay Ex-tubation following surgery.
- Willingness to provide informed consent.
Who cannot join
- Other significant medical conditions that may interfere with study participation.
- Prior exposure to Efgartigimod.
- Male patients who do not intend to use effective contraception during trail or within last dosing
- Pateints with worsening muscle weekness due to concurrent infection or medications known to exacerbate MG.
- Patients with known or active seropositive HBV,HCV, HIV.
- Patients with documented lack of clinical response to Flax.
Show all 12Show fewer
- Use of any investigational drug within 3 month or 5 helf -lives prior to screening.
- Avidance of significant disease ,recent major surgery or renal/ hepatic function who can put patient at undue risk.
- Previous participation in clinic trail involving ARGX-113
- Vaccination recived whitin 4 weeks prior screening using live or attenuated vaccinations.
- Patient Calssified MGFA Class 1
- Pregnant and lactating women
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site
Rambam- Department of Neurology
Haifa, 3109601
Shahar Shelly, Dr, +9723451995, s_shelly@rambam.health.gov.il
Chen Tikotzki, C_TIKOTZKI@rambam.health.gov.il
About this study
Efgartigimod in Myasthenic Crisis Background Myasthenia gravis (MG) is a prevalent autoimmune disorder affecting neuromuscular junctions, characterized by weakness in skeletal muscles. It is associated with the production of autoantibodies, primarily targeting acetylcholine receptors (AchR), and is often complicated by myasthenic crisis, which can lead to severe respiratory failure. Current treatments primarily involve non-specific immunosuppression, which may not provide rapid relief.
Aim This study investigates the therapeutic impact of efgartigimod, an FcRn-targeting Fc fragment, on patients experiencing a myasthenic crisis. We hypothesize that efgartigimod is non-inferior to conventional treatments like intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) in terms of clinical efficacy and safety.
Read more
Study Rationale Efgartigimod aims to reduce pathogenic IgG autoantibodies implicated in MG by accelerating their degradation. This targeted approach could provide faster symptom relief during acute exacerbations compared to existing therapies.
Objectives Primary Objective: To assess the non-inferiority of efgartigimod compared to PLEX and IVIG based on MG-ADL improvements.
Secondary Objectives: Evaluate safety, tolerability, length of hospital stay, respiratory parameters, need for additional therapies, and one-year outcomes.
Primary Endpoint MG-ADL Improvement: Defined as a ≥3-point improvement post-treatment. The comparison will be made using one-month post-treatment assessments, with follow-ups every three months.
Secondary Endpoints Safety and tolerability Length of hospital stay Changes in respiratory function Need for rescue therapy in case of clinical deterioration Sample Size The study will recruit 32 patients (16 historical group and 16 interventional group), calculated to detect significant differences in MG-ADL improvements with a significance level of 0.05 and power of 0.80.
Patient Recruitment Patients with a confirmed diagnosis of MG who present to the neurology department will be recruited and randomly assigned to either the efgartigimod treatment group or the historical control group receiving standard care (IVIG/PLEX).
Inclusion Criteria Adults > 18 years Confirmed MG diagnosis with generalized weakness (MGFA class II-V) Positive AchR or MuSK antibodies Evidence of myasthenic crisis Informed consent Exclusion Criteria Contraindications to efgartigimod Significant comorbidities affecting study participation Prior exposure to efgartigimod Ongoing infections or conditions exacerbating MG symptoms Recent major surgery or significant renal/hepatic dysfunction Planned Protocol Administer efgartigimod intravenously at 10 mg/kg weekly for four weeks. Total trial duration: 12 months for enrollment and treatment, followed by a 14-month follow-up.
Read the detailed description
Study Rationale: The study rationale for investigating the effectiveness of IV efgartigimod in myasthenic crisis hinges on the need for treatments that can provide rapid and targeted relief from the acute exacerbations of MG, which are life-threatening. Current treatments, while potentially effective, can be associated with significant side effects and may not work swiftly enough to address the urgent needs of a myasthenic crisis. Efgartigimod, an FcRn antagonist, has been designed to reduce the circulating levels of pathogenic IgG autoantibodies, which are implicated in the pathophysiology of MG. By accelerating the degradation of these autoantibodies, efgartigimod could potentially offer a faster onset of action and improve clinical outcomes in patients during a myasthenic crisis
- Conditions
- Myasthenia Gravis Crisis
- Being tested
- IV efgartigimod
- Keywords
- Myasthenia Gravis Crisis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV efgartigimodDrug
Also called vyvgart
IV efgartigimod
| Study group | Role | What they receive |
|---|---|---|
| Interventional group with Efgartigimod | Experimental | Efgartigimod will be given to patients with MG CRISIS Receives: Drug: IV efgartigimod |
| Historical PLEX group | No intervention | this group is the retrospective arm |
What is being measured
The primary outcome is the main question the study is designed to answer.
MG-ADL scores observed before and after treatment initiation
Descriptive statistics will be used to summarize the characteristics of the study population. Kaplan-Meier curves to estimate the probability of cancer over time in cumulative analysis curves. A two-tailed p-value <0.05 was considered statistically significant
Measured: 14 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2024
- Study start15 Nov 2024 (estimated)
- Primary completion15 Jan 2025 (estimated)
- Study completion30 Mar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Myasthenia Gravis CrisisStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rambam Health Care Campus
- Sponsor type
- University, hospital or other
- Collaborators
- argenx
- Responsible party
- Principal investigator, . Shahr Shelly MD, Rambam Health Care Campus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06688253
- Sponsor's protocol ID
- rambam271
- Status last verified
- Nov 2024
- First submitted
- 5 Nov 2024
- Last updated
- 14 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Shelly S, Rosenberg A, Zoabi M, Makhoul S, Ramon-Gonen R, Wolfe GI. Prospective study of efgartigimod in severe myasthenia gravis exacerbations requiring ventilatory or enteral support. J Neuromuscul Dis. 2026 Aug 4:22143602261450402. doi: 10.1177/22143602261450402. Online ahead of print.
PubMed 42551446
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravenous Human IgG1 Fc Fragment (Efgartigimod) in Myasthenic Crisis
- ClinicalTrials.gov ID
- NCT06688253
- Acronym / sponsor ID
- rambam271
- Conditions
- Myasthenia Gravis Crisis
- Keywords
- Myasthenia Gravis Crisis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Rambam Health Care CampusUniversity, hospital or other
- Collaborators
- argenx
- Study start
- 15 Nov 2024 (estimated)
- Primary completion
- 15 Jan 2025 (estimated)
- Study completion
- 30 Mar 2025 (estimated)
- First posted
- 14 Nov 2024 (actual)
- 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.
Efgartigimod in Myasthenic Crisis Background Myasthenia gravis (MG) is a prevalent autoimmune disorder affecting neuromuscular junctions, characterized by weakness in skeletal muscles. It is associated with the production of autoantibodies, primarily targeting acetylcholine receptors (AchR), and is often complicated by myasthenic crisis, which can lead to severe respiratory failure. Current treatments primarily involve non-specific immunosuppression, which may not provide rapid relief.
Aim This study investigates the therapeutic impact of efgartigimod, an FcRn-targeting Fc fragment, on patients experiencing a myasthenic crisis. We hypothesize that efgartigimod is non-inferior to conventional treatments like intravenous immunoglobulin (IVIG) and plasma exchange (PLEX) in terms of clinical efficacy and safety.
Study Rationale Efgartigimod aims to reduce pathogenic IgG autoantibodies implicated in MG by accelerating their degradation. This targeted approach could provide faster symptom relief during acute exacerbations compared to existing therapies.
Objectives Primary Objective: To assess the non-inferiority of efgartigimod compared to PLEX and IVIG based on MG-ADL improvements.
Secondary Objectives: Evaluate safety, tolerability, length of hospital stay, respiratory parameters, need for additional therapies, and one-year outcomes.
Primary Endpoint MG-ADL Improvement: Defined as a ≥3-point improvement post-treatment. The comparison will be made using one-month post-treatment assessments, with follow-ups every three months.
Secondary Endpoints Safety and tolerability Length of hospital stay Changes in respiratory function Need for rescue therapy in case of clinical deterioration Sample Size The study will recruit 32 patients (16 historical group and 16 interventional group), calculated to detect significant differences in MG-ADL improvements with a significance level of 0.05 and power of 0.80.
Patient Recruitment Patients with a confirmed diagnosis of MG who present to the neurology department will be recruited and randomly assigned to either the efgartigimod treatment group or the historical control group receiving standard care (IVIG/PLEX).
Inclusion Criteria Adults > 18 years Confirmed MG diagnosis with generalized weakness (MGFA class II-V) Positive AchR or MuSK antibodies Evidence of myasthenic crisis Informed consent Exclusion Criteria Contraindications to efgartigimod Significant comorbidities affecting study participation Prior exposure to efgartigimod Ongoing infections or conditions exacerbating MG symptoms Recent major surgery or significant renal/hepatic dysfunction Planned Protocol Administer efgartigimod intravenously at 10 mg/kg weekly for four weeks. Total trial duration: 12 months for enrollment and treatment, followed by a 14-month follow-up.
Detailed description
Study Rationale: The study rationale for investigating the effectiveness of IV efgartigimod in myasthenic crisis hinges on the need for treatments that can provide rapid and targeted relief from the acute exacerbations of MG, which are life-threatening. Current treatments, while potentially effective, can be associated with significant side effects and may not work swiftly enough to address the urgent needs of a myasthenic crisis. Efgartigimod, an FcRn antagonist, has been designed to reduce the circulating levels of pathogenic IgG autoantibodies, which are implicated in the pathophysiology of MG. By accelerating the degradation of these autoantibodies, efgartigimod could potentially offer a faster onset of action and improve clinical outcomes in patients during a myasthenic crisis
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Interventional group with Efgartigimod | Experimental | Drug: IV efgartigimodEfgartigimod will be given to patients with MG CRISIS |
| Historical PLEX group | No intervention | –this group is the retrospective arm |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- -Age > 18
- MG diagnosis
- A confirmed diagnosis of Myasthenia Gravis (MG) with generalized muscle weakness, classified as MGFA class II, III, IVa, or IVb and V.
- Positive AchR or MuSK antibodies (max three patients of the total cohort) this will be tested in our center for all patients.
- Myasthenic crisis: Worsening of > 3 or an increase >1 MG-ADL points of a sub score of any individual MG-ADL item other than double vision or eyelid droop and its clinically significant by the investigator. Alternatively, weakness related to MG that is severe enough to necessitate intubation or delay Ex-tubation following surgery.
Key exclusion criteria (12 listed)
- Other significant medical conditions that may interfere with study participation.
- Prior exposure to Efgartigimod.
- Male patients who do not intend to use effective contraception during trail or within last dosing
- Pateints with worsening muscle weekness due to concurrent infection or medications known to exacerbate MG.
- Patients with known or active seropositive HBV,HCV, HIV.
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 |
|---|---|---|
| IV efgartigimodAlso: vyvgartIV efgartigimod | Drug | Interventional group with Efgartigimod |
Primary outcome
MG-ADL scores observed before and after treatment initiation
Time frame: 14 month
Descriptive statistics will be used to summarize the characteristics of the study population. Kaplan-Meier curves to estimate the probability of cancer over time in cumulative analysis curves. A two-tailed p-value <0.05 was considered statistically significant
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2024.
- Derived from this study: PubMed 42551446Shelly S, Rosenberg A, Zoabi M, Makhoul S, Ramon-Gonen R, Wolfe GI. Prospective study of efgartigimod in severe myasthenia gravis exacerbations requiring ventilatory or enteral support. J Neuromuscul Dis. 2026 Aug 4:22143602261450402. doi: 10.1177/22143602261450402. Online ahead of print.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing IV efgartigimod in people with Myasthenia Gravis Crisis, run by Rambam Health Care Campus at 1 site in Israel.
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 6 inclusion and 12 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: opening soon, as of the sponsor's last update on 14 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shahar Shelly, Dr (+972543541995 ext. +972047773987, s_shelly@rambam.health.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MG-ADL scores observed before and after treatment initiation (time frame: 14 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06688253, which also lists 1 linked publication.
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 14 Nov 2024.