MEthotrexate versus TOcilizumab for treatment of GIant cell Arteritis: a multicenter, randomized, controlled trial - METOGIA
- Conditions
- MedDRA version: 20.0 Level: LLT Classification code 10018250 Term: Giant cell arteritis System Organ Class: 100000004866Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2018-002826-22-FR
- Lead Sponsor
- CHU Dijon Bourgogne
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 200
- Written consent
- Affiliation to a social security system
- Diagnosis of GCA, as defined by the revised GCA diagnosis criteria:
o Age =50 years at disease onset
o AND History of erythrocyte sedimentation rate (ESR) =50 mm/h OR CRP=20 mg/L (not mandatory if TAB is positive: see below)
o AND At least one of the following:
* unequivocal cranial symptoms of GCA (new onset headache, scalp tenderness, jaw claudication, temporal artery abnormality, ischemia-related vision loss)
* unequivocal symptoms of polymyalgia rheumatica (PMR)
o AND At least one of the following:
* Temporal artery biopsy (TAB) compatible with the diagnosis of GCA (non-necrotizing vasculitis with a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells)
* AND/OR Evidence of large vessel vasculitis (aorta and/or epiaortic arteries):
• angio-CT or angio-MRI: thickened arterial wall (=2mm for the aorta and =1mm for epiaortic arteries) and/or contrast-enhanced arteries in T1-weighted sequences
• PET scan: grade 3 tracer uptake of the arterial wall (grade 3 = arterial SUVmax superior to the SUVmax of the liver)
- Active GCA within 6 weeks before randomization. Active GCA is defined by ESR =30 mm/h or CRP =10 mg/L and at least one of the following:
o =1 unequivocal cranial symptoms of GCA (new onset localized headache, scalp or temporal artery tenderness, ischemia-related vision loss, or otherwise unexplained mouth or jaw pain upon mastication)
o OR =1 unequivocal symptoms of PMR, defined as shoulder and/or hip girdle pain associated with inflammatory stiffness
o OR any other feature(s) judged by the clinical investigator to be consistent with GCA or PMR flares
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
- Uncontrolled psychotic state
- Patient unable to give his/her consent
- Premenopausal women (menopause is defined as amenorrhea for more than 12 consecutive months)
- Non-compliant patients
- Weight<40 Kg or >100Kg
- Patient under maintenance of justice, wardship or legal guardianship
- History of intoxication (alcohol or medication) requiring hospitalization within 12 months before inclusion
- History of chronic alcohol abuse (consumption > 20g/day)
- Recent or incoming surgery within 12 months after inclusion
- History of stem cell or organ transplantation (except corneas if performed more than 3 months prior inclusion)
- Primary or secondary immunodeficiency
- Hypersensitivity to methotrexate or tocilizumab, one of its excipients or another human or murine monoclonal antibody
- History of diverticulitis, inflammatory bowel disease, or other symptomatic gastrointestinal tract condition that might predispose to bowel perforation
- Prior treatment with any of the following:
o Tocilizumab or methotrexate within 12 weeks before inclusion
o Cell-depleting agents (i.e., anti-CD20)
o Alkylating agents including cyclophosphamide
o Hydroxychloroquine, cyclosporine A, dapsone, azathioprine or mycophenolate mofetil or janus kinase inhibitors within 4 weeks before inclusion
o Tumor necrosis factor inhibitors within 8 weeks (infliximab) or 2 weeks (adalimumab or etanercept) before inclusion
o Anakinra within 1 week before inclusion
- Long-term systemic glucocorticoid therapy for other conditions than GCA or PMR
- Patient with =3 prior glucocorticoid systemic therapies for another disease than GCA or PMR within 6 months before inclusion
- Long-term treatment with sulfamethoxazole/trimethoprim (Bactrim®)
- Live vaccine administered within 30 days before inclusion
- Laboratory abnormalities:
o AST or ALT >1.5 x upper limit of normal (ULN)
o total bilirubin >ULN
o platelets<100 G/L
o leukocytes <3 G/L
o neutropenia <1.5 G/L
o lymphopenia <0.5 G/L
o clearance of creatinine <30 ml/min/1,73 m2 [CKD EPI 2009]
o positive HBs antigens or positive HCV antibodies
- Infections:
o History of viral hepatitis B or C (chronic or acute)
o HIV infection
o Persistent infection or severe infection requiring hospitalization or intravenous antibiotics within 30 days before inclusion (antibiotic treatment tests are allowed, regardless of duration and route of administration)
o Proven infection requiring oral antibiotics within 14 days before inclusion (antibiotic treatment tests are allowed, regardless of duration and route of administration)
o Prior history of histoplasmosis or listeriosis
o Active tuberculosis
o Signs of latent tuberculosis (based on a history of non-treated contact, opacity with a diameter greater than 1 cm on chest radiography, or positive in vitro test: Quantiferon Gold® or T-Spot-TB®).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: ;Secondary Objective: ;Primary end point(s):
- Secondary Outcome Measures
Name Time Method