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NCT02950155: Rinomax

A Study Evaluating the Safety and Efficacy of Rituximab in Patients With Myasthenia Gravis

Completed Phase 3 Results posted Last updated 26 October 2024
What this trial tests

Phase 3 trial testing Rituximab in Generalized Myasthenia Gravis in 47 participants. Completed in 31 January 2022.

Timeline
16 October 2016
Primary endpoint
30 January 2021
31 January 2022

Quick facts

Lead sponsorFredrik Piehl
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment47
Start date16 October 2016
Primary completion30 January 2021
Estimated completion31 January 2022
Sites1 location across Sweden

Drugs / interventions tested

Conditions studied

Sponsor

Fredrik Piehl

Who can join

18 and older, any sex, with Generalized Myasthenia Gravis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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. Primary · 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.

GroupValue95% CI
Rituximab17
Sodium Chloride Solution6
Change in QMG Score From Week 0 to Week 24 After Administration of Study Drug/Placebo. Secondary · 24 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 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.

GroupValue95% CI
Rituximab-6.9± 5.6
Sodium Chloride Solution-5.8± 4.6
Change in Myasthenia Gravis Activities of Daily Living (MG-ADL) Score From Week 0 to Week 16 After Administration of Study Drug/Placebo Secondary · 16 weeks

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.

GroupValue95% CI
Rituximab-1.7± 2.5
Sodium Chloride Solution-0.5± 3.6
Change in Myasthenia Gravis Quality of Life (QoL) Score From Week 0 to Week 16 After Administration of Study Drug/Placebo. Secondary · 16 weeks

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. .

GroupValue95% CI
Rituximab-9.2± 9.2
Sodium Chloride Solution-7.0± 9.3
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. Secondary · 24 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 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.

GroupValue95% CI
Rituximab18
Sodium Chloride Solution8
Number of Hospital Admissions for MG Worsening During Week 0 to 24 After Administration of Study Drug/Placebo Secondary · 24 weeks

The total number of hospital admissions for MG worsening during week 0 to 24 of the study.

GroupValue95% CI
Rituximab0
Placebo3
Rescue Treatments During Week 8 to 24 After Administration of Study Drug/Placebo Secondary · 8 - 24 weeks

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).

GroupValue95% CI
Rituximab1
Placebo8

Adverse events — posted to ClinicalTrials.gov

Time frame: 48 weeks, i.e. time from baseline to last follow up.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rituximab
Serious: 5/25 (20%)
Deaths: 1/25
Sodium Chloride Solution
Serious: 4/22 (18%)
Deaths: 0/22

Serious adverse events (10 terms)

ReactionSystemRituximabSodium Chloride Solution
Chest painCardiac disorders
AnemiaBlood and lymphatic system disorders
PneumoniaInfections and infestations
SepticaemiaInfections and infestations
NauseaNervous system disorders
IleusGastrointestinal disorders
AsystoleCardiac disorders
Vertebral compression fractureMusculoskeletal and connective tissue disorders
SyncopeCardiac disorders
ThymomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (19 terms — click to expand)

ReactionSystemRituximabSodium Chloride Solution
Upper respiratory infectionInfections and infestations
Musculoskeletal painMusculoskeletal and connective tissue disorders
DiarrheaGastrointestinal disorders
Muscle crampsMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
Allergic reactionSkin and subcutaneous tissue disorders
Dry mouthGastrointestinal disorders
ArrythmiaCardiac disorders
ConjunctivitisEye disorders
Fever of unknown causeInfections and infestations
NauseaGastrointestinal disorders
Rectal bleedingGastrointestinal disorders
FatigueGeneral disorders
AnemiaBlood and lymphatic system disorders
VertigoEar and labyrinth disorders
Urine leaksRenal and urinary disorders
Urinary tract infectionRenal and urinary disorders
Bite from animal (dog)Injury, poisoning and procedural complications
Kidney stoneRenal and urinary disorders

Most-reported serious reactions: Chest pain, Anemia, Pneumonia, Septicaemia, Nausea, Ileus, Asystole, Vertebral compression fracture.

Data from ClinicalTrials.gov NCT02950155 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis: The RINOMAX Randomized Clinical Trial.
    Piehl F, Eriksson-Dufva A, Budzianowska A, Feresiadou A, et al · · 2022 · cited 132× · PMID 36121672 · DOI 10.1001/jamaneurol.2022.2887
  2. Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology.
    Fichtner ML, Jiang R, Bourke A, Nowak RJ, et al · · 2020 · cited 98× · PMID 32547535 · DOI 10.3389/fimmu.2020.00776
  3. Comparison Between Rituximab Treatment for New-Onset Generalized Myasthenia Gravis and Refractory Generalized Myasthenia Gravis.
    Brauner S, Eriksson-Dufva A, Hietala MA, Frisell T, et al · · 2020 · cited 81× · PMID 32364568 · DOI 10.1001/jamaneurol.2020.0851
  4. Outcome Measures in Clinical Trials of Patients With Myasthenia Gravis.
    Thomsen JLS, Andersen H. · · 2020 · cited 47× · PMID 33424747 · DOI 10.3389/fneur.2020.596382
  5. New Pathways and Therapeutic Targets in Autoimmune Myasthenia Gravis.
    Behin A, Le Panse R. · · 2018 · cited 39× · PMID 30010142 · DOI 10.3233/jnd-170294
  6. Refocusing generalized myasthenia gravis: Patient burden, disease profiles, and the role of evolving therapy.
    Saccà F, Salort-Campana E, Jacob S, Cortés-Vicente E, et al · · 2024 · cited 33× · PMID 38117543 · DOI 10.1111/ene.16180
  7. From Traditional to Targeted Immunotherapy in Myasthenia Gravis: Prospects for Research.
    Mantegazza R, Antozzi C. · · 2020 · cited 30× · PMID 32982957 · DOI 10.3389/fneur.2020.00981
  8. Antibody Therapies in Autoimmune Neuromuscular Junction Disorders: Approach to Myasthenic Crisis and Chronic Management.
    Vanoli F, Mantegazza R. · · 2022 · cited 26× · PMID 35165857 · DOI 10.1007/s13311-022-01181-3

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