A French multicenter randomised and placebo-controlled study recruiting patients who present neurovascular involvement related to GCA (\> 60 years) with symptomatic (stroke) or asymptomatic forms. The aim of this study is to assess the efficacy of tocilizumab to induce complete remission of GCA with cerebrovascular involvement (clinical and biological) and absence of clinical and MRI ischemic stroke recurrence at 24 weeks.
Giant cell arteritis (GCA) in the elderly is considered a medical emergency in case of ischemic complication, urgent treatment is needed and high doses of intravenous steroids are used. To date, usual treatments added to steroids have not been shown to be effective in reducing the risk of ischemic event recurrence in GCA. Recently, the efficacy of tocilizumab has been demonstrated as a steroid-sparing agent and a long-term complete remission agent. The aim of this study is to address the potential benefits of tocilizumab as induction therapy in combination with high dose steroids to improve the neurovascular involvement in GCA. The study will enroll 66 subjects with GCA (according to ACR criteria or positive temporal artery biopsy) and neurovascular involvement (symptomatic or asymptomatic). It consist of a screening phase (up to 30 days), a baseline/randomization phase and a treatment phase with experimental treatment or placebo (weekly administrated) which could be combined with usual treatments for stroke as antiaggregants and/or anticoagulants (24 weeks). Regular visit will be performed to follow the GCA remission, adverse treatments effects and proceed to radiological and biological evaluations (visit assessment at weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36) until end of study visit at week 52.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
66
Tocilizumab will be administered subcutaneously at a dose of 162mg/0.9mL weekly (each week, on the same day) from week 0 to week 24. At the first injection (Baseline D0), a therapeutic education is provided for patients/caregivers who can carry out the injections themselves as part of their usual care.
Placebo administered subcutaneously (SC) weekly during 24 weeks
Saint Antoine Hospital, Neurology Unit, Assistance Publique-Hôpitaux de Paris
Paris, France
Percentage of patients in complete remission of GCA with absence of ischemic stroke recurrence at 24 weeks under tocilizumab.
Percentage of participants with complete remission of GCA, defined as an absence of clinical signs of GCA, a CRP levels less than 10 mg/l and an absence of new ischemic stroke signs at MRI realized at 24 weeks after the tocilizumab initiation
Time frame: From date of treatment initiation until 24 weeks.
Compare within tocilizumab and placebo groups the percentage of clinical and MRI ischemic stroke recurrence at 24 weeks
the efficacy of weekly tocilizumab on the prevention of stroke recurrence will be measured by the percentage of stroke recurrence compared to control group in patients with GCA during 52 weeks at week 4, 12, 24 and 52
Time frame: at week 4, 12, 24 and 52.
The relapse-free survival
Number of patients who had relapsed as defined as major if clinical symptoms are present, or as minor in the case of isolated acute pase reactants increase
Time frame: up to 52 weeks
Compare within tocilizumab and placebo groups the time to remission in patients with GCA during 52 weeks.
the time to remission will be assessed in comparison with the control group in patients with GCA during 52 weeks at week 4, 12, 24 and 52 Number of days between treatment induction and signs of remission.
Time frame: at week 4, 12, 24 and 52.
Compare within tocilizumab and placebo groups the improvement of neurovascular radiological involvement during 52 weeks
Proportion of patient with neurovascular radiological involvement defined as angio-CT improvement of vasculitis lesions and /or improvement or disappearance of PET FDG uptake.
Time frame: at week 4, 12, 24 and 52.
Compare within tocilizumab and placebo groups the steroid sparing effect at 24 weeks
Cumulative steroid dose at 24 weeks
Time frame: up to 24 weeks
Mortality at week 4, 12, 24 and 52
Percentages of deaths at week 4, 12, 24 and 52.
Time frame: at week 4, 12, 24 and 52
Evolution of degree of disability or dependence at week 4, 12, 24 and 52
Percentages of patients with rankin score 0-1
Time frame: at week 4, 12, 24 and 52.
Percentage of Participants with Adverse Events/ serious adverse events
Percentage of participants with adverse events, treatment-related adverse events or serious adverse event as assessed by CTCAE v4.0, at week 4, 12, 24 and 52
Time frame: at week 4, 12, 24 and 52.
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