Myasthenia Gravis, GeneralizedPhase 3REFINENCT05868837
Rituximab EfFicacy IN MyasthEnia Gravis (REFINE)
A Phase 3 study testing Rituximab in people with Myasthenia Gravis, Generalized, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
Trial summary
The primary objective of this phase III trial is to investigate if Rituximab can reduce patients' functional impairment caused by MG. The secondary objectives of this trial are to assess whether treatment with rituximab in patients with MG will: Allow faster and greater corticosteroid tapering Reduce the frequency of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myasthenia Gravis, Generalized
- What is being tested?
- Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- 28 Feb 2022to 31 Jul 2025
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Positive serologic test for anti-AChR or anti-MuSK antibody titers as confirmed at screening (one retest allowed), and
- At least one of the following:
- i)-History of abnormal neuromuscular transmission test results demonstrated by single- fiber electromyography or repetitive nerve stimulation; or ii)-History of positive anticholinesterase test (eg, edrophonium chloride test); or iii)-Patient demonstrated improvement in MG signs on oral cholinesterase inhibitors, as assessed by the treating physician; or iv)-Clinical syndrome consistent with a diagnosis of MG, and not otherwise explained by another condition. c. MGFA Clinical Classification Class II, III, or IV at the time of screening and randomization.
- MG-ADL score of 5 or greater at screening and at randomization with \> 50% of this score attributed to non-ocular items. e. QMG score of 11 or greater at screening and at randomization. f. Willing and able to comply with the protocol, complete study assessments, and return for follow- up visits.
- Females of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective contraception method (Table 1) from the time of screening and for 12 months after the final dose of IP. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. h. Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not postmenopausal (defined as 12 months with no menses without an alternative medical cause).
- Non-sterilized males who are sexually active with a female partner of childbearing potential must use a condom from Day 1 for the duration of the study and for 3 months after the last dose of IP. Because male condom is not a highly effective contraception method, it is strongly recommended that female partners of a male study subject also use a highly effective method of contraception throughout this period.
Who cannot join
- Any condition that, in the opinion of the Investigator, would place the patient at unacceptable risk of complications, interfere with evaluation of the IP, or confound the interpretation of patient safety or study results.
- Lactating or pregnant females, or females who intend to become pregnant anytime from signing the informed consent form (ICF) throughout the RCP plus 6 months following last dose of IP.
- History of drug or alcohol abuse within < 1 year prior to screening, or any condition associated with poor compliance as judged by the Investigator.
- Site staff and their family members.
- Currently committed to an institution by way of official or judicial order.
- Subjects diagnosed with congenital myasthenic syndromes.
Show all 23Show fewer
- Known immunodeficiency disorder, including human immunodeficiency virus (HIV) infection.
- Thymectomy within ≤ 12 months prior to baseline (Day 1) visit or planned thymectomy during the duration of the RCP.
- 10. Receipt of the following medications or treatments at any time prior to randomization:
- Alemtuzumab (Lemtrada®, Campath®)
- Total lymphoid irradiation
- Bone marrow transplant
- T-cell vaccination therapy
- Natalizumab (Tysabri®) 10. Receipt of ANY immunosuppressive treatment (excluding corticosteroids) at ANY time prior to randomization (such as Azathioprine, Mycophenolate mofetil or Mycophenolic acid, Cyclosporine (except eye drop), Tacrolimus (except topical), Methotrexate, Cyclophosphamide, Tocilizumab (Actemra®), Belimumab (Benlysta®), Eculizumab (Soliris®), rituximab (MabThera®, Rituxan®), ocrelizumab (Ocrevus®), ofatumumab (Arzerra®), obinutuzumab (Gazyva®), inebilizumab, or any experimental B-cell depleting agent) 11. Receipt within the 4 weeks prior to Day 1:
- Intravenous immunoglobulin (IVIg) b. Plasma exchange (PLEX) treatment 12. Current use of:
- Prednisone < 20 mg/day or < 40 mg over a 2-day period (or equivalent dose of other corticosteroids)
- Pyridostigmine > 480 mg/day or unstable dose in the 2 weeks prior to Day 1 13. Concurrent/previous enrollment in another clinical study involving an investigational treatment within 4 weeks or 5 half-lives of the investigational treatment, whichever is longer, prior to Day 1.
- 14. Receipt of a live attenuated vaccine within 4 weeks prior to randomization. Administration of inactivated (killed) vaccines is acceptable. 15. History of severe allergic or anaphylactic reactions to biologic agents or known allergy to any component of the IP formulation. 16. History of recurrent significant infections (eg, requiring hospitalization or IV antibiotics).
- 17. Within 2 weeks prior to the screening visit: clinically significant active infection requiring antimicrobial medication but allowing chronic nail infections. 18. Unresected thymoma (Note: subjects with a benign thymoma resected > 1 year prior to screening may enroll. Benign is defined as no known metastases and no extension into or beyond the capsule on pathological examination. Imaging to evaluate for thymoma must have been performed prior to randomization per standard of care). 19. History of cancer, except for the following:
- In situ carcinoma of the cervix treated with apparent success with curative therapy for > 12 months prior to screening b. Cutaneous basal cell or squamous cell carcinoma treated with apparent success with curative therapy for > 12 months prior to screening c. Prostate cancer treated with radical prostatectomy or radiation therapy with curative intent > 3 years prior to screening and without known recurrence or current treatment d. Malignant thymoma (i.e. Masaoka stage ≥ IIa) resected > 5 years prior to screening with no evidence of active disease and no therapy received over the previous 5 years. Imaging to evaluate for thymoma must have been performed prior to randomization per standard of care 21. Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to screening.
- 22. Any of the following laboratory abnormalities at screening (one repeat test may be conducted to confirm results prior to randomization within the same screening period):
- Elevated liver enzymes (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN)). b. Total bilirubin > 1.5 × ULN (unless due to Gilbert's syndrome) c. Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2 d. CD19+ B-cell count < 40 cells/μL e. Absolute neutrophil count (ANC) < 1.2 × 103 cells/μl f. Platelet count < 75,000/μL (or < 75 × 109/L) g. Hemoglobin < 8.0 g/dL h. Total immunoglobulin < 600 mg/dL 23. Positive test for chronic hepatitis B infection at screening, defined as either (1) positive hepatitis B surface antigen (HBsAg) or (2) a positive hepatitis B core antibody (anti-HBc) PLUS negative hepatitis B surface antibody (anti-HBs). Note: Subjects with a positive anti-HBs only, or a positive anti-HBc plus positive anti-HBs and negative HBsAg, are eligible to enroll. 24. Positive test for hepatitis C virus antibody. 25. Positive HIV test. 26. Blood transfusion within 4 weeks prior to screening or during the screening period.
- 27. Inability to read. 28. History of active or latent tuberculosis (TB), or a positive QuantiFERON®-TB Gold test at screening, unless treatment for tuberculosis was completed per local guidelines. Subjects with latent TB or a positive QuantiFERON®-TB Gold test who are actively on anti-TB treatment can enroll if they have completed at least 1 month of anti-TB treatment and intend to complete the full course of anti-TB treatment. Subjects with an indeterminate QuantiFERON®-TB Gold test result can enroll if a repeat QuantiFERON®-TB Gold is negative or a tuberculin skin test is negative.
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Policlinico A. Gemelli IRCCS
Roma, 00168
Raffaele Iorio, +393347185128, raffaele.iorio@policlinicogemelli.it
About this study
Official title: Single-cell Deep Phenotyping of B Lymphocytes to Personalize Immunotherapy in Patients With Myasthenia Gravis: Clinical Trial to Evaluate the Efficacy and Safety of Rituximab in Generalized AChR-antibody Positive Myasthenia Gravis
The primary objective of this phase III trial is to investigate if Rituximab can reduce patients' functional impairment caused by MG. The secondary objectives of this trial are to assess whether treatment with rituximab in patients with MG will:
- Allow faster and greater corticosteroid tapering
- Reduce the frequency of exacerbations
- Improve quality of life
- Offer an acceptable safety and tolerability profile.
- Conditions
- Myasthenia Gravis, Generalized
- Being tested
- Rituximab, Placebo
- 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, Rituxan
Rituximab 1000 mg IV on RCP days 1 and 15
PlaceboOther
Placebo 1000 mg IV on RCP days 1 and 15
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Rituximab will be provided in 500mg/50ml vials; excipients include sodium chloride, tri-sodium citrate dihydrate, polysorbate 80, water for injections. Two vials will be diluted in 500 ml of sodium chloride 0,9% to reach a concentration of 2mg/ml. Rituximab will be administered intravenously in two 1000 mg infusions, with two weeks distance between the first and the second infusion. Receives: Drug: Rituximab |
| Placebo | Placebo comparator | Placebo will consist of 500 ml flacons of sodium chloride 0,9%. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess whether rituximab can reduce MG-related functional impairment.
Change from baseline in Quantitative Myasthenia Gravis Score (QMG) at week 12 (3 months) of the RCP.
QMG score 0 - 39 A higher score means a worse outcome
Measured: 12 weeks
Secondary outcomes (2)
To evaluate the effect of rituximab on corticosteroid usage.
Change in corticosteroid dosage from week 12 to the end of the RCP.
Measured: 48 weeks
To evaluate the effect of rituximab on MG-related disability.
Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) score at week 12.
MG-ADL score 0 - 24 A higher score means a worse outcome
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2023
- Study start28 Feb 2022
- Primary completion31 Jul 2025 (estimated)
- Study completion31 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myasthenia Gravis, GeneralizedStudies of the same condition, open and under way.
- More trials run by Fondazione Policlinico Universitario Agostino Gemelli IRCCSThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Raffaele Iorio, Principal investigator, Fondazione Policlinico Universitario Agostino Gemelli IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05868837
- Sponsor's protocol ID
- 3916
- Acronym
- REFINE
- Status last verified
- Sep 2024
- First submitted
- 11 May 2023
- Last updated
- 1 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single-cell Deep Phenotyping of B Lymphocytes to Personalize Immunotherapy in Patients With Myasthenia Gravis: Clinical Trial to Evaluate the Efficacy and Safety of Rituximab in Generalized AChR-antibody Positive Myasthenia Gravis
- ClinicalTrials.gov ID
- NCT05868837
- Acronym / sponsor ID
- REFINE / 3916
- Conditions
- Myasthenia Gravis, Generalized
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Fondazione Policlinico Universitario Agostino Gemelli IRCCSUniversity, hospital or other
- Study start
- 28 Feb 2022 (actual)
- Primary completion
- 31 Jul 2025 (estimated)
- Study completion
- 31 Jul 2025 (estimated)
- First posted
- 22 May 2023 (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.
The primary objective of this phase III trial is to investigate if Rituximab can reduce patients' functional impairment caused by MG. The secondary objectives of this trial are to assess whether treatment with rituximab in patients with MG will:
- Allow faster and greater corticosteroid tapering
- Reduce the frequency of exacerbations
- Improve quality of life
- Offer an acceptable safety and tolerability profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RituximabRituximab will be provided in 500mg/50ml vials; excipients include sodium chloride, tri-sodium citrate dihydrate, polysorbate 80, water for injections. Two vials will be diluted in 500 ml of sodium chloride 0,9% to reach a concentration of 2mg/ml. Rituximab will be administered intravenously in two 1000 mg infusions, with two weeks distance between the first and the second infusion. |
| Placebo | Placebo comparator | Other: PlaceboPlacebo will consist of 500 ml flacons of sodium chloride 0,9%. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Positive serologic test for anti-AChR or anti-MuSK antibody titers as confirmed at screening (one retest allowed), and
- i)-History of abnormal neuromuscular transmission test results demonstrated by single- fiber electromyography or repetitive nerve stimulation; or ii)-History of positive anticholinesterase test (eg, edrophonium chloride test); or iii)-Patient demonstrated improvement in MG signs on oral cholinesterase inhibitors, as assessed by the treating physician; or iv)-Clinical syndrome consistent with a diagnosis of MG, and not otherwise explained by another condition. c. MGFA Clinical Classification Class II, III, or IV at the time of screening and randomization.
- MG-ADL score of 5 or greater at screening and at randomization with \> 50% of this score attributed to non-ocular items. e. QMG score of 11 or greater at screening and at randomization. f. Willing and able to comply with the protocol, complete study assessments, and return for follow- up visits.
- Females of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective contraception method (Table 1) from the time of screening and for 12 months after the final dose of IP. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. h. Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not postmenopausal (defined as 12 months with no menses without an alternative medical cause).
- Non-sterilized males who are sexually active with a female partner of childbearing potential must use a condom from Day 1 for the duration of the study and for 3 months after the last dose of IP. Because male condom is not a highly effective contraception method, it is strongly recommended that female partners of a male study subject also use a highly effective method of contraception throughout this period.
Key exclusion criteria (23 listed)
- Any condition that, in the opinion of the Investigator, would place the patient at unacceptable risk of complications, interfere with evaluation of the IP, or confound the interpretation of patient safety or study results.
- Lactating or pregnant females, or females who intend to become pregnant anytime from signing the informed consent form (ICF) throughout the RCP plus 6 months following last dose of IP.
- History of drug or alcohol abuse within < 1 year prior to screening, or any condition associated with poor compliance as judged by the Investigator.
- Site staff and their family members.
- Currently committed to an institution by way of official or judicial order.
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: MabThera, RituxanRituximab 1000 mg IV on RCP days 1 and 15 | Drug | Rituximab |
| PlaceboPlacebo 1000 mg IV on RCP days 1 and 15 | Other | Placebo |
Primary outcome
To assess whether rituximab can reduce MG-related functional impairment.
Time frame: 12 weeks
Change from baseline in Quantitative Myasthenia Gravis Score (QMG) at week 12 (3 months) of the RCP. QMG score 0 - 39 A higher score means a worse outcome
2 secondary outcomes
To evaluate the effect of rituximab on corticosteroid usage.
Time frame: 48 weeks
To evaluate the effect of rituximab on MG-related disability.
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
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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.
Raffaele Iorio principal investigator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
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 in people with Myasthenia Gravis, Generalized, run by Fondazione Policlinico Universitario Agostino Gemelli IRCCS at 1 site in Italy.
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 23 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: status not confirmed, as of the sponsor's last update on 1 Aug 2025. 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 Italy. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Raffaele Iorio (+393347185128, raffaele.iorio@policlinicogemelli.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess whether rituximab can reduce MG-related functional impairment. (time frame: 12 weeks). 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 1 Aug 2025.