Rituximab EfFicacy IN MyasthEnia Gravis (REFINE)

NCT05868837 | Recruiting Phase 3

• 1 other identifier: 3916
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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 exacerbations
• Improve quality of life
• Offer an acceptable safety and tolerability profile.

Conditions

Myasthenia Gravis, Generalized

Outcome Measures

Primary Outcomes (1)

• 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

  12 weeks

Secondary Outcomes (2)

• To evaluate the effect of rituximab on corticosteroid usage.

  48 weeks

• To evaluate the effect of rituximab on MG-related disability.

  12 weeks

Study Arms (2)

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.

Drug: Rituximab

Placebo

PLACEBO COMPARATOR

Placebo will consist of 500 ml flacons of sodium chloride 0,9%.

Other: Placebo

Interventions

Rituximab DRUG

Rituximab 1000 mg IV on RCP days 1 and 15

Also known as: MabThera, Rituxan

Rituximab

Placebo OTHER

Placebo 1000 mg IV on RCP days 1 and 15

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• a. 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.
• d. 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.
• g. 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).
• i. 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.

You may not qualify if:

• 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.
• 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.
• \. 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:
• a. Intravenous immunoglobulin (IVIg) b. Plasma exchange (PLEX) treatment 12. Current use of:

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Policlinico A. Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Raffaele Iorio

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Raffaele Iorio

CONTACT

+393347185128; raffaele.iorio@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2023
• First Posted: May 22, 2023
• Study Start: February 28, 2022
• Primary Completion: July 31, 2025
• Study Completion: July 31, 2025
• Last Updated: August 1, 2025

Record last verified: 2024-09

Locations

IT (1)