Status:
ACTIVE_NOT_RECRUITING
Efficacy of Tocilizumab in Association to Steroids in Giant Cell Arteritis With Cerebro-vascular Involvement
Lead Sponsor:
Assistance Publique - Hôpitaux de Paris
Collaborating Sponsors:
Roche Chugai
Roche Pharma AG
Conditions:
Giant Cell Arteritis
Neurovascular Disorder
Eligibility:
All Genders
60+ years
Phase:
PHASE3
Brief Summary
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...
Detailed Description
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...
Eligibility Criteria
Inclusion
- Age \> 60 years
- Diagnosis of
- GCA (according to ACR criteria or positive temporal artery biopsy) (de novo and/or relapse) And neurovascular involvement:
- Either Ischemic stroke (including TIA) in the vertebro-basilar or carotid territory (symptomatic arterial involvement)
- Either PET uptake of vertebral and/or carotid arteries (extra or intra cranial) and/or angioCT or angioMRI showing arterial involvement consistent with vasculitis (asymptomatic arterial involvement)
- Inclusion should be done
- within 4 weeks after the stroke concerning the "symptomatic" patients
- within 4 weeks after the diagnosis of GCA (or relapse) concerning the patients with asymptomatic neurovascular involvement.
- Within 21 days after starting the corticosteroids
- Signed Informed Consent Form
- Affiliation to social security
Exclusion
- Other proven cause of stroke: atrial fibrillation, significant atheromatous stenosis of carotid or vertebro-basilar arteries
- Contraindication to and precaution in use of tocilizumab:
- Treatment with any investigational agent within 12 weeks (or 5 half-lives of the investigational drug, whichever was longer) of screening
- Previous treatment with cell-depleting therapies, including investigational agents,including but not limited to Campath (alemtuzumab), anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20 within 6 months before the baseline
- Treatment with IV gamma globulin or plasmapheresis within 24 weeks of baseline
- Previous treatment with alkylating agents, such as chlorambucil, or with total lymphoid irradiation within 2 months before the baseline
- Previous treatment with TCZ within 6 months before the baseline
- Immunization with a live/attenuated vaccine within 4 weeks prior to baseline or simultaneously with tocilizumab treatment
- Treatment with hydroxychloroquine, cyclosporine A, azathioprine, or mycophenolate mofetil (MMF) within 4 weeks of baseline
- Treatment with etanercept within 2 weeks; infliximab, certolizumab, golimumab,abatacept, or adalimumab within 8 weeks; or anakinra within 1 week of baseline
- Previous treatment with tofacitinib within 2 months before the baseline
- Treatment with cyclophosphamide within 24 weeks of baseline
- History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies or to prednisone
- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus), psychiatric, osteoporosis/osteomalacia, glaucoma, corneal ulcers/injuries, or gastrointestinal disease
- Current liver disease, as determined by the investigator
- History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower GI disease such as Crohn's disease, ulcerative colitis, or other symptomatic lower GI conditions that might predispose a patient to perforations
- Known active current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections (including but not limited to tuberculosis \[TB\] and atypical mycobacterial disease, hepatitis B and C, and herpes zoster, but excluding fungal infections of the nail beds)
- Any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks of screening
- Active TB requiring treatment within the previous 3 years
- Patients treated for TB with no recurrence within 3 years and patients treated for latent TB within 3 years were eligible.
- Primary or secondary immunodeficiency (history of or currently active)
- Evidence of malignant disease or malignancies diagnosed within the previous 5 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that had been excised and cured)
- History of alcohol, drug, or chemical abuse within 1 year prior to screening
- Body weight \>150 kg
- Serum creatinine \>1.4 mg/dL (124 µmol/L) in female patients and 1.6 mg/dL (141 µmol/L) in male patients
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)× 3 Upper limit of normal (ULN)\>
- Platelet count \< 100 109/L (100,000/mm3)
- Hemoglobin \< 85 g/L (8.5 g/dL; 5.3 mmol/L)
- White blood cells \<3.0 x109/L (3000/mm3)
- Absolute neutrophil count \< 2.0 x 109/L (2000/mm3)
- Absolute lymphocyte count \< 0.5 X 109/L (500/mm3)
- Positive hepatitis B surface antigen or hepatitis C antibody
- Contraindication to aspirin, clopidogrel, steroids use, rifampicin and/or isoniazid
- Major surgery within 8 weeks prior to screening or planned major surgery within 12 months after randomization, except arterial thrombectomy if necessary for ischemic stroke
- Transplanted organs (except corneal transplant performed more than 3 months prior to screening)
- Inability to provide informed consent
- Participation in another interventional research
Key Trial Info
Start Date :
September 24 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
August 13 2025
Estimated Enrollment :
66 Patients enrolled
Trial Details
Trial ID
NCT04888221
Start Date
September 24 2021
End Date
August 13 2025
Last Update
June 25 2025
Active Locations (1)
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1
Saint Antoine Hospital, Neurology Unit, Assistance Publique-Hôpitaux de Paris
Paris, France, 75012