BOSENTAN for Giant cell arteritis

Inclusion criteria

• {"criterion_text":"- Patients having given their written informed consent prior to participation in the study.\n- Patients affiliated with social security or CMU (profit or being entitled)\n- Diagnosis of GCA, as defined by the revised GCA diagnosis criteria. Patients must satisfy criteria 1-2-3 and 4 (irrespective of time): 1.\tAge ≥50 years at disease onset 2.\tHistory of erythrocyte sedimentation rate (ESR) ≥ 50 mm/h or CRP ≥ 20 mg/L (not mandatory if TAB is positive: see below) 3.\tAt 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) 4.\tAt 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) - Evidence of large vessel vasculitis: o\tangio-CT or angio-MRI: thickened and/or contrast-enhanced arteries especially aorta (≥2mm) and epiaortic arteries (≥1mm) and contrast enhanced arteries in T1-weighted sequences o\tor PET scan: ≥ grade 2 (from 0 to 3) tracer uptake on large arteries\n- At least a sign of active GCA within the 4 weeks prior to randomisation. Active GCA is defined by ESR ≥30 mm/h or CRP ≥10 mg/L and at least one of the following: o\tunequivocal 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\tunequivocal symptoms of PMR, defined as shoulder and/or hip girdle pain associated with inflammatory stiffness o\tother features judged by the clinical investigator to be consistent with GCA or PMR flares\n- Menopausal women (no gynaecological cycle over the past two years), or women who had a gynaecological cycle within previous 24 months (non-menopausal women) only if they have (1) an effective non hormonal contraceptive method throughout study and (2) a negative urinary beta-hCG test at inclusion."}

Exclusion criteria

• {"criterion_text":"- Patients under maintenance of justice, wardship or legal guardianship\n- History of stem cell or organ transplantation (except corneas if performed more than 3 months prior inclusion)\n- Hypersensitivity to bosentan or one of its excipients\n- Prior treatment with any of the following: o\tTocilizumab or methotrexate or secukinumab within 12 weeks preceding inclusion o\tCell-depleting agents (i.e., anti-CD20) o\tAlkylating agents including cyclophosphamide o\tHydroxychloroquine, cyclosporine A, dapsone, azathioprine, mycophenolate mofetil or janus kinase inhibitors within 4 weeks preceding inclusion o\tTumor necrosis factor inhibitors within 8 weeks preceding inclusion o\tAnakinra within 1 week preceding inclusion\n- Ongoing treatment with glibenclamide, fluconazole and rifampicin. Concomitant administration of both a CYP3A4 inhibitor or a CYP2C9 inhibitor\n- Long-course systemic glucocorticoid therapy for other conditions than GCA or PMR\n- Laboratory abnormalities: AST or ALT >3 x upper limit of normal (ULN)\n- Infections: o\tActive hepatitis B or C o\tHIV infection\n- Patient unable to give written informed consent prior to participation in the study\n- Patients included in other investigational therapeutic study within the previous 3 months\n- Patients suspected not to be observant to the proposed treatments\n- Pregnant or breastfeeding woman\n- Weight <40 Kg or > 100 Kg\n- Moderate to severe hepatic impairment, i.e., Child-Pugh class B or C. History of chronic alcohol abuse (consumption > 20 g/day\n- Severe chronic heart failure or severe systolic dysfunction\n- Recent (< 3 months) or incoming surgery requiring a general anaesthesia"}

Primary endpoints

• {"endpoint_text":"- Failure free survival at W52. A failure is defined by the occurrence of a relapse or the impossibility to decrease GC according to the predefined scheduled GC scheme.","definition_or_measurement_approach":"Failure free survival measured at Week 52; failure defined as occurrence of relapse or inability to decrease glucocorticoids according to the predefined scheduled glucocorticoid scheme."}

Secondary endpoints

• {"endpoint_text":"- 1)\tProportion of new ischemic event at W 52","definition_or_measurement_approach":"Proportion of patients with a new ischemic event measured at Week 52."}
• {"endpoint_text":"- 2)\tProportion of patients in remission without prednisone at W52","definition_or_measurement_approach":"Proportion of patients in remission without prednisone measured at Week 52."}
• {"endpoint_text":"- 3)\tProportion of patients in remission with prednisone ≤5 mg/day at W52","definition_or_measurement_approach":"Proportion of patients in remission with prednisone ≤5 mg/day measured at Week 52."}
• {"endpoint_text":"- 4)\tCumulative dose of prednisone at W52","definition_or_measurement_approach":"Cumulative prednisone dose assessed at Week 52."}
• {"endpoint_text":"- 5)\tQuality of life measured by HAQ and SF36 at W 26 and W52","definition_or_measurement_approach":"Quality of life assessed using HAQ and SF-36 instruments at Weeks 26 and 52."}
• {"endpoint_text":"- 6)\tProportion of patient in remission at year 2","definition_or_measurement_approach":"Proportion of patients in remission measured at year 2 (24 months)."}
• {"endpoint_text":"- Secondary objectives and endpoints\t•\tSECONDARY objectives •\tEFFICACY: 1) To compare the occurrence of new ischemic event 2) To compare (bosentan versus reference group) the proportion of patients in remission without prednisone at W52 3) To compare (bosentan versus reference group) the proportion of patients in remission with ≤5 mg/day of prednisone at W52 4) To assess the GC-sparing effect of bosentan in the treatment of GCA 5) To assess the effect of bosentan on quality of life 6) To compare","definition_or_measurement_approach":"Composite listing of secondary efficacy objectives comparing bosentan versus reference group for ischemic events, remission rates, GC-sparing effect and quality of life; measurement timepoints include Week 52 and Year 2 where indicated."}
• {"endpoint_text":"- 8)\tProportion of patients receiving GC at year 2","definition_or_measurement_approach":"Proportion of patients still receiving glucocorticoids at year 2 (24 months)."}
• {"endpoint_text":"- 1) Frequency and type of side effects within 1 year after inclusion","definition_or_measurement_approach":"Frequency and characterization of adverse events within 1 year after inclusion."}

France

Earliest CTIS Part Ii Submission Date

25-07-2025

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

243

Number Of Sites

20

Number Of Participants

40

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France