A clinical trial investigating the effect and safety of the drug rituximab in patients with new onset myasthenia gravis, an autoimmune condition affecting muscle strenght

• Register: EUCTR
• Last refreshed on: 6 December 2021
• Main ID: EUCTR2015-005749-30-SE
• Date of registration: 28/04/2016
• Prospective Registration: Yes
• Primary sponsor: Karolinska Institutet
• Public title: A clinical trial investigating the effect and safety of the drug rituximab in patients with new onset myasthenia gravis, an autoimmune condition affecting muscle strenght
• Scientific title: A randomized, doubleblind, placebo-controlled multicenter trial to evaluate the safety and efficacy of rituximab (Mabthera) in subjects with new onset myasthenia gravis; the RINOMAX study - Rinomax
• Date of first enrolment: 23/06/2016
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-005749-30
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Sweden

Contacts

• Name: Neuroimmunology Unit CMM L8;4
• Affiliation: Karolinska Institutet

• Name: Neuroimmunology Unit CMM L8;4
• Affiliation: Karolinska Institutet

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with oculo bulbar, bulbar or generalized MG = 18 years of age and not more than 12 months ago estimated the onset of symptoms of generalized symptoms or neurophysiological detection of generalized disease.
2. The diagnosis of MG should be produced by the following tests:
Clinical neurological status with motor effects consistent with MG, and at least two of the following:
A positive serological test for anti-acetylcholine receptor antibodies (AChR),
and / or
b. For MG typical deviation during neurophysiological testing of the neuromuscular transmission with single fiber electromyography (SFEMG) and / or repetitive nerve stimulation (RNS)
and/or
c Positive choline esterase blocker response, e.g. edrophonium and/or oral cholinesterase inhibitors, as judged by the treating physician.
3. MGFA clinical classification Class II to IV at screening.
4. Quantitative MG score = 6 at screening
5. Women of childbearing potential must have a negative pregnancy test.
6. Patients must have given written informed consent.
7. Patients must be able and willing to comply with all study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
1. Weakness that only affect ocular or periocular muscles (MGFA class I).
2. MG crisis at screening (MGFA Class V)
3. Already implemented thymectomy. In order to avoid difficulties to evaluate the effect of the study drug, thymectomy, in cases where it is indicated, should be scheduled to the follow-up period, ie after the first 24 weeks.
4. Strong suspicion of thymoma, where a thymectomy is indicated within 24 weeks according to the treating physician.
5. Active tumor disease, if not adequately treated.
6. Pregnancy and lactation.
7. 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 antibiotics / antiviral drug.
8. Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease.
9. 9. Previously use of immunosuppressive drugs, including rituximab, azathioprine, cyclosporine and MMF. Prednisolone at a dose of =40mg / d within 3 months and IVIG and PLEX 12 months of the screening date is not an exclusion criterion. Also note that this does not apply to treatment with immunosuppressive drugs / corticosteroids (except rituximab) in another indication than MG, provided that it is > 12 months since the treatment ended.10. Hypersensitivity to the active substance or to murine proteins or to any of the excipients of the study drug
11. Participation in another trial to study drug or exposure to any other study drugs, study product or study procedures within 30 days prior to screening.
12. Any medical condition which, according to the study physician's opinion, may interfere with the patient's participation in the study, pose any additional risk to the patient, or that complicate the assessment of patients


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

New onset myasthenia gravis
MedDRA version: 20.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders

Intervention(s)

Trade Name: Mabthera
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Primary end point(s): Percentage of patients with a QMG score =4 and daily prednisone dose =10mg 16 weeks after treatment

Secondary Objective: Is Rituximab more effective than placebo in achieving improvement in standardized QMG at 24 weeks after treatment?

Is Rituximab more effective than placebo in achieving improvement in the ability to perform activities of daily live at 16 weeks after treatment?

Is Rituximab more effective than placebo in achieving improvement in experienced quality of life at 16 weeks after treatment?

Main Objective: To evaluate if rituximab is more effective than placebo to achieve minimal clinical MG symptoms without need of high doses of oral corticosteroids at 16 weeks after treatment

Timepoint(s) of evaluation of this end point: At 16 weeks after treatment

Secondary Outcome(s)

Secondary end point(s): QMG score at 24 weeks after treatment
MG-ADL score at 16 weeks after treatment
MG-QOL scores at 16 weeks after treatment

Timepoint(s) of evaluation of this end point: At 16 and 24 weeks after treatment

Secondary ID(s)

2015-00887

Source(s) of Monetary Support

Swedish Research Council

Ethics review

Status: Approved
Approval date: 15/06/2016
Contact: