Generalized Myasthenia GravisPhase 3RinomaxNCT02950155
A Study Evaluating the Safety and Efficacy of Rituximab in Patients With Myasthenia Gravis
A Phase 3 study testing Rituximab and Sodium Chloride solution in people with Generalized Myasthenia Gravis, run by Fredrik Piehl at 1 site in Sweden.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Generalized Myasthenia Gravis
- What is being tested?
- Rituximab and Sodium Chloride solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 47 participants
- Where
- 1 siteSweden
- Study dates
- 16 Oct 2016to 31 Jan 2022
- Phase
- Phase 3
- 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 with oculobulbar, bulbar or generalized MG ≥ 18 years of age and with onset of generalized symptoms or neurophysiological detection of generalized disease not more than 12 months ago.
- 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.
- MGFA Class II to IV at screening.
- Quantitative MG score ≥ 6 at screening
Show all 9Show fewer
- Women of childbearing potential must have a negative pregnancy test.
- Patients must have provided written informed consent.
- Patients must be able and willing to comply with all study procedures.
Who cannot join
- Weakness only affecting ocular or periocular muscles (MGFA Class I).
- MG crisis at screening (MGFA Class V)
- Thymectomy already carried out. In order to avoid difficulties to evaluate the effect of the study drug, thymectomy, where it is indicated, should be scheduled to the follow-up period, ie after the first 24 weeks.
- Strong suspicion of thymoma, where thymectomy as judged by the treating physician should be done within 24 weeks.
- Active malignancy, if not adequately treated
- Pregnancy or breast-feeding.
Show all 13Show fewer
- Ongoing acute or chronic viral or systemic bacterial infections including HIV, latent hepatitis B, which is clinically significant, according to the study doctor's opinion and not treated with appropriate antibiotic / antiviral drugs.
- Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease
- Previous use of immunosuppressive drugs, including rituximab, except prednisolone at a dose of up to 40mg daily for less than 3 months. This does not apply to treatment with immunosuppressive drugs / corticosteroids (except rituximab) for other indications than MG, provided at least 12 months have passed since treatment was terminated.
- Suspected hypersensitivity to the study drug
- Participation in another trial of study drug within 30 days prior to screening.
- Any medical condition which, according to the study physician's opinion, may interfere with the patient's participation in the study, poses additional risks for the patient, or that complicate the assessment of patients.
- Vaccination within 4 weeks before inclusion.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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)
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).
Read the detailed description
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.
- Conditions
- Generalized Myasthenia Gravis
- Being tested
- Rituximab, Sodium Chloride solution
- Medical subject headings
- Myasthenia Gravis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
Also called Mabthera
A single infusion at a dose of 500 mg Mabthera/Rituximab.
Sodium Chloride solutionDrug
Also called Sodium Chloride
A single infusion of Placebo/Sham.
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | A single infusion at a dose of 500 mg of Mabthera/Rituximab. Receives: Drug: Rituximab |
| Sodium Chloride solution | Sham comparator | A single infusion with sodium chloride solution. Receives: Drug: Sodium Chloride solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 16 weeks
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Oct 2016 (estimated)
- Study start16 Oct 2016
- Primary completion30 Jan 2021
- Study completion31 Jan 2022
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Generalized 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fredrik Piehl
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Fredrik Piehl, Karolinska Institutet
- Investigators
- Fredrik Piehl, Professor, Principal investigator, Dept Clinical Neuroscience Karolinska Institutet, Neuroimmunology Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02950155
- Sponsor's protocol ID
- EudraCT 2015-005749-30
- Acronym
- Rinomax
- Status last verified
- Aug 2024
- First submitted
- 28 Oct 2016
- Last updated
- 26 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Piehl F, Eriksson-Dufva A, Budzianowska A, Feresiadou A, Hansson W, Hietala MA, Hakansson I, Johansson R, Jons D, Kmezic I, Lindberg C, Lindh J, Lundin F, Nygren I, Punga AR, Press R, Samuelsson K, Sundstrom P, Wickberg O, Brauner S, Frisell T. Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial. JAMA Neurol. 2022 Nov 1;79(11):1105-1112. doi: 10.1001/jamaneurol.2022.2887.
PubMed 36121672
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT02950155
- Acronym / sponsor ID
- Rinomax / EudraCT 2015-005749-30
- Conditions
- Generalized Myasthenia Gravis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Fredrik PiehlUniversity, hospital or other
- Study start
- 16 Oct 2016 (actual)
- Primary completion
- 30 Jan 2021 (actual)
- Study completion
- 31 Jan 2022 (actual)
- First posted
- 31 Oct 2016 (estimated)
- Results
- Posted 26 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RituximabA single infusion at a dose of 500 mg of Mabthera/Rituximab. |
| Sodium Chloride solution | Sham comparator | Drug: Sodium Chloride solutionA single infusion with sodium chloride solution. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with oculobulbar, bulbar or generalized MG ≥ 18 years of age and with onset of generalized symptoms or neurophysiological detection of generalized disease not more than 12 months ago.
- 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.
- MGFA Class II to IV at screening.
Key exclusion criteria (13 listed)
- Weakness only affecting ocular or periocular muscles (MGFA Class I).
- MG crisis at screening (MGFA Class V)
- Thymectomy already carried out. In order to avoid difficulties to evaluate the effect of the study drug, thymectomy, where it is indicated, should be scheduled to the follow-up period, ie after the first 24 weeks.
- Strong suspicion of thymoma, where thymectomy as judged by the treating physician should be done within 24 weeks.
- Active malignancy, if not adequately treated
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 |
|---|---|---|
| RituximabAlso: MabtheraA single infusion at a dose of 500 mg Mabthera/Rituximab. | Drug | Rituximab |
| Sodium Chloride solutionAlso: Sodium ChlorideA single infusion of Placebo/Sham. | Drug | Sodium Chloride solution |
Primary outcome
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.
Time frame: 16 weeks
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.
3 secondary outcomes
Change in QMG Score From Week 0 to Week 24 After Administration of Study Drug/Placebo.
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
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.
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36121672Piehl F, Eriksson-Dufva A, Budzianowska A, Feresiadou A, Hansson W, Hietala MA, Hakansson I, Johansson R, Jons D, Kmezic I, Lindberg C, Lindh J, Lundin F, Nygren I, Punga AR, Press R, Samuelsson K, Sundstrom P, Wickberg O, Brauner S, Frisell T. Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial. JAMA Neurol. 2022 Nov 1;79(11):1105-1112. doi: 10.1001/jamaneurol.2022.2887.
- 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.
Fredrik Piehl, Professor principal investigator
Dept Clinical Neuroscience Karolinska Institutet, Neuroimmunology Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Rituximab and Sodium Chloride solution in people with Generalized Myasthenia Gravis, run by Fredrik Piehl at 1 site in Sweden.
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 9 inclusion and 13 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 26 Oct 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 Sweden. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 26 Oct 2024). 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?
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. (time frame: 16 weeks). 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 NCT02950155, 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 26 Oct 2024.