A Phase 3 interventional study of Rituximab and Sodium Chloride solution in Generalized Myasthenia Gravis, sponsored by Fredrik Piehl. Completed at 1 site in Sweden. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-26.
Sponsored by Fredrik Piehl · Phase 3, Interventional, and Treatment
A randomized, double-blind, placebo-controlled multicenter study evaluating the safety and efficacy of Rituximab (Mabthera®) in patients with new onset generalized myasthenia gravis (MG).
Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction caused by auto-antibodies. MG is characterized by weakness in skeletal muscles and occurs in all ages, but mostly among young adult women and in people of both sexes over the age of 60 years. The disease has a wide variation in severity, where in milder cases only symptom-relieving choline esterase blockers may be sufficient. In many cases, however, immunomodulatory drugs are required. Traditionally MG has been treated with high doses of corticosteroids over longer time periods, which causes significant risks of side effects. Therefore, since several decades, oral immunosuppressive drugs have been used in order to reduce the need for steroids. This group includes azathioprine, cyclosporine and mycophenolate. However, none of these drugs has been approved for use in MG and the effect is usually delayed. There is thus a great need to develop newer treatment algorithms for MG, for example including more effective biological drugs. Several small observational studies have shown that rituximab, an anti-CD20 monoclonal antibody that eliminate B cells, can have good effects in treatment refractory MG. The aim of the present study is to study the effect of rituximab compared to placebo in the treatment of new onset MG of moderate to severe symptomatology.
324 studies on the registry are indexed under Myasthenia Gravis; 146 are open to participants now.
This study's enrollment of 47 is close to the median of 44 across 212 interventional studies indexed under Myasthenia Gravis.
Browse Myasthenia Gravis studies →This is the only study on the registry with Fredrik Piehl as lead sponsor.
Counted across the registry records on this site, refreshed daily.
The diagnosis of MG should be determined with the following:
Clinical neurological status with motor symptoms consistent with MG and at least two of the following:
a positive serologic test for anti-acetylcholine receptor antibody (AChR) and/or b. typical MG findings on neurophysiological testing of neuromuscular transmission with single fiber electromyography (SFEMG) and / or repetitive nerve stimulation (RNS), and / or c. Positive anti-choline esterase-test, e.g. edrophoniumchloride or improvement of MG symptoms with oral cholinesterase inhibitors as judged by the treating physician.
Exclusion Criteria:
A single infusion at a dose of 500 mg of Mabthera/Rituximab.
Drug: Rituximab
A single infusion with sodium chloride solution.
Drug: Sodium Chloride solution
A single infusion at a dose of 500 mg Mabthera/Rituximab.
Also known as: Mabthera
A single infusion of Placebo/Sham.
Also known as: Sodium Chloride
Percentage of Patients With Quantitative MG Score (QMG) Score ≤ 4 and a Daily Prednisolon Dose of ≤ 10mg at 16 Weeks After Administration of Study Drug/Placebo.
The Quantitative Myasthenia Gravis (QMG) score is a physician rated disease activity score that ranges from 0 to 39, where lower indicates better outcome. QMG was measured at 16 weeks under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Patients meeting the primary outcome had a QMG score of 4 or less whilst also requiring a daily oral Prednisolone dose of 10 mg or less.
Time frame: 16 weeks
Change in QMG Score From Week 0 to Week 24 After Administration of Study Drug/Placebo.
The Quantitative Myasthenia Gravis (QMG) score is a physician rated disease activity score that ranges from 0 to 39, where lower indicates better outcome. QMG was measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Change in QMG scores between the two time points was compared between groups.
Time frame: 24 weeks
Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) Score From Week 0 to Week 16 After Administration of Study Drug/Placebo
The Myasthenia Gravis Activities of Daily Living (MG-ADL) score is a patient rated disease activity score that ranges from 0 to 24, where lower indicates better outcome. MG-ADL was assessed at 16 weeks under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Change in MG-ADL scores between the two time points was compared between groups.
Time frame: 16 weeks
Change in Myasthenia Gravis Quality of Life (QoL) Score From Week 0 to Week 16 After Administration of Study Drug/Placebo.
The Myasthenia Quality of Life (QoL) score is a patient rated quality of life score that ranges from 0 to 60, where lower indicates better outcome. Change in MG-QoL scores between the two time points was compared between groups. .
Time frame: 16 weeks
Percentage of Patients With Quantitative MG Ascore (QMG) Score ≤ 4 and a Daily Prednisolon Dose of ≤ 10mg at 24 Weeks After Administration of Study Drug/Placebo.
The Quantitative Myasthenia Gravis (QMG) score is a physician rated disease activity score that ranges from 0 to 39, where lower indicates better outcome. QMG was measured at 24 weeks under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Patients meeting the primary outcome had a QMG score of 4 or less whilst also requiring a daily oral Prednisolone dose of 10 mg or less.
Time frame: 24 weeks
QMG Scores at 16, 36 and 48 Weeks After Administration of Study Drug/Placebo.
QMG is measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
Time frame: 16, 36 and 48 weeks
MG-activities of Daily Living (ADL) Score at 24, 36 and 48 Weeks After Administration of Study Drug/Placebo
MG-ADL is a patient-reported outcome measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
Time frame: 24, 36 and 48 weeks
EQ5D Score at 16, 24, 36 and 48 Weeks After Administration of Study Drug/Placebo
The EQ5D scale is a generic QoL score measured under standardized conditions with at least 12 hours since last intake of choline e
Time frame: 16, 24, 36 and 48 weeks
MG-QoL Score at 24, 36 and 48 Weeks After Administration of Study Drug/Placebo
MG-QoL is a patient-reported outcome measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
Time frame: 24, 36 and 48 weeks
Number of Hospital Admissions for MG Worsening During Week 0 to 24 After Administration of Study Drug/Placebo
The total number of hospital admissions for MG worsening during week 0 to 24 of the study.
Time frame: 24 weeks
Rescue Treatments During Week 8 to 24 After Administration of Study Drug/Placebo
The number of events when rescue treatment was given during week 8-24 of the study. Rescue treatments were defined as i.v immunoglobulins, plasma exchange, high dose corticosteroids and biologics (rituximab, tocilizumab).
Time frame: 8 - 24 weeks
Between October 16th, 2016, and March 2nd, 2020, 87 potentially eligible patients were screened at 7 Swedish neurology clinics (5 university hospitals, 2 regional hospitals). 47 fulfilled inclusion and exclusion criteria and provided informed consent to participation.
| Milestone | Rituximab | Placebo |
|---|---|---|
| Started | 25 | 22 |
| Completed | 25 | 22 |
| Not completed | 0 | 0 |
The Quantitative Myasthenia Gravis (QMG) score is a physician rated disease activity score that ranges from 0 to 39, where lower indicates better outcome. QMG was measured at 16 weeks under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Patients meeting the primary outcome had a QMG score of 4 or less whilst also requiring a daily oral Prednisolone dose of 10 mg or less.
| Participants | Rituximab | Sodium Chloride Solution |
|---|---|---|
| Percentage of Patients With Quantitative MG Score (QMG) Score ≤ 4 and a Daily Prednisolon Dose of ≤ 10mg at 16 Weeks After Administration of Study Drug/Placebo. | 17 | 6 |
The Quantitative Myasthenia Gravis (QMG) score is a physician rated disease activity score that ranges from 0 to 39, where lower indicates better outcome. QMG was measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Change in QMG scores between the two time points was compared between groups.
| change in score points | Rituximab | Sodium Chloride Solution |
|---|---|---|
| Change in QMG Score From Week 0 to Week 24 After Administration of Study Drug/Placebo. | -6.9 ± 5.6 | -5.8 ± 4.6 |
The Myasthenia Gravis Activities of Daily Living (MG-ADL) score is a patient rated disease activity score that ranges from 0 to 24, where lower indicates better outcome. MG-ADL was assessed at 16 weeks under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Change in MG-ADL scores between the two time points was compared between groups.
| change in score points | Rituximab | Sodium Chloride Solution |
|---|---|---|
| Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) Score From Week 0 to Week 16 After Administration of Study Drug/Placebo | -1.7 ± 2.5 | -0.5 ± 3.6 |
The Myasthenia Quality of Life (QoL) score is a patient rated quality of life score that ranges from 0 to 60, where lower indicates better outcome. Change in MG-QoL scores between the two time points was compared between groups. .
| change in score points | Rituximab | Sodium Chloride Solution |
|---|---|---|
| Change in Myasthenia Gravis Quality of Life (QoL) Score From Week 0 to Week 16 After Administration of Study Drug/Placebo. | -9.2 ± 9.2 | -7.0 ± 9.3 |
The Quantitative Myasthenia Gravis (QMG) score is a physician rated disease activity score that ranges from 0 to 39, where lower indicates better outcome. QMG was measured at 24 weeks under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors. Patients meeting the primary outcome had a QMG score of 4 or less whilst also requiring a daily oral Prednisolone dose of 10 mg or less.
| Participants | Rituximab | Sodium Chloride Solution |
|---|---|---|
| Percentage of Patients With Quantitative MG Ascore (QMG) Score ≤ 4 and a Daily Prednisolon Dose of ≤ 10mg at 24 Weeks After Administration of Study Drug/Placebo. | 18 | 8 |
QMG is measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
Results for this outcome have not been posted.
MG-ADL is a patient-reported outcome measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
Results for this outcome have not been posted.
The EQ5D scale is a generic QoL score measured under standardized conditions with at least 12 hours since last intake of choline e
Results for this outcome have not been posted.
MG-QoL is a patient-reported outcome measured under standardized conditions with at least 12 hours since last intake of choline esterase inhibitors
Results for this outcome have not been posted.
The total number of hospital admissions for MG worsening during week 0 to 24 of the study.
| hospital adminssions | Rituximab | Placebo |
|---|---|---|
| Number of Hospital Admissions for MG Worsening During Week 0 to 24 After Administration of Study Drug/Placebo | 0 | 3 |
The number of events when rescue treatment was given during week 8-24 of the study. Rescue treatments were defined as i.v immunoglobulins, plasma exchange, high dose corticosteroids and biologics (rituximab, tocilizumab).
| events | Rituximab | Placebo |
|---|---|---|
| Rescue Treatments During Week 8 to 24 After Administration of Study Drug/Placebo | 1 | 8 |
Collected over 48 weeks, i.e. time from baseline to last follow up.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Rituximab | 1/25 (4%) | 5/25 (20%) | 21/25 (84%) |
| Sodium Chloride Solution | 0/22 (0%) | 4/22 (18.2%) | 17/22 (77.3%) |
| Event | Rituximab | Sodium Chloride Solution |
|---|---|---|
| Chest painCardiac disorders | 2/25 | 0/22 |
| AnemiaBlood and lymphatic system disorders | 0/25 | 1/22 |
| PneumoniaInfections and infestations | 0/25 | 1/22 |
| SepticaemiaInfections and infestations | 0/25 | 1/22 |
| AsystoleCardiac disorders | 0/25 | 1/22 |
| ThymomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/25 | 1/22 |
| NauseaNervous system disorders | 1/25 | 0/22 |
| IleusGastrointestinal disorders | 1/25 | 0/22 |
| Vertebral compression fractureMusculoskeletal and connective tissue disorders | 1/25 | 0/22 |
| SyncopeCardiac disorders | 1/25 | 0/22 |
| Event | Rituximab | Sodium Chloride Solution |
|---|---|---|
| Upper respiratory infectionInfections and infestations | 6/25 | 8/22 |
| Musculoskeletal painMusculoskeletal and connective tissue disorders | 8/25 | 4/22 |
| DiarrheaGastrointestinal disorders | 5/25 | 2/22 |
| Muscle crampsMusculoskeletal and connective tissue disorders | 5/25 | 1/22 |
| RashSkin and subcutaneous tissue disorders | 2/25 | 4/22 |
| Allergic reactionSkin and subcutaneous tissue disorders | 3/25 | 2/22 |
| ArrythmiaCardiac disorders | 0/25 | 2/22 |
| NauseaGastrointestinal disorders | 2/25 | 2/22 |
| Dry mouthGastrointestinal disorders | 2/25 | 0/22 |
| ConjunctivitisEye disorders | 2/25 | 0/22 |
| Age, Categorical(Participants) | Rituximab | Sodium Chloride Solution | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 15 | 14 | 29 |
| >=65 years | 10 | 8 | 18 |
| Age, Continuous(years) | Rituximab | Sodium Chloride Solution | Total |
|---|---|---|---|
| Mean | 67.4 ± 13.4 | 58.0 ± 18.6 | 63.0 ± 16.6 |
| Sex: Female, Male(Participants) | Rituximab | Sodium Chloride Solution | Total |
|---|---|---|---|
| Female | 7 | 7 | 14 |
| Male | 18 | 15 | 33 |
| Race and Ethnicity Not Collected(Participants) | Rituximab | Sodium Chloride Solution | Total |
|---|---|---|---|
| Count of participants | — | — | 0 |
| Region of Enrollment(participants) | Rituximab | Sodium Chloride Solution | Total |
|---|---|---|---|
| Sweden | 25 | 22 | 47 |
| Body mass index(kg/m^2) | Rituximab | Sodium Chloride Solution | Total |
|---|---|---|---|
| Mean | 27.5 ± 3.7 | 27.6 ± 5.7 | 27.5 ± 4.7 |
| Concentration of acetylcholine receptor antibodies(nmol/L) | Rituximab | Sodium Chloride Solution | Total |
|---|---|---|---|
| Mean | 22.7 ± 19.3 | 70.7 ± 117 | 46.7 ± 86.5 |
| Time since onset of generalized symptoms of myasthenia gravis(days) | Rituximab | Sodium Chloride Solution | Total |
|---|---|---|---|
| Mean | 132.4 ± 91.5 | 143.0 ± 93.3 | 137.4 ± 91.5 |
9 further baseline measures are reported on the registry.
Documents are hosted by the registry — open the source record to download them.
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