- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04888221
Efficacy of Tocilizumab in Association to Steroids in Giant Cell Arteritis With Cerebro-vascular Involvement (TOGIAC)
Efficacy of Tocilizumab in Association to Steroids in Giant Cell Arteritis With Cerebro-vascular Involvement (ToGiAC)
Study Overview
Status
Conditions
Intervention / Treatment
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 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
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Sonia ALAMOWITCH, PU-PH
- Phone Number: + (33)1-49-28-06-51
- Email: sonia.alamowitch@aphp.fr
Study Contact Backup
- Name: Arsène MEKINIAN, PU-PH
- Phone Number: + (33)01-48-95-0765
- Email: arsene.mekinian@sat.aphp.fr
Study Locations
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-
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Paris, France, 75012
- Recruiting
- Saint Antoine Hospital, Neurology Unit, Assistance Publique-Hôpitaux de Paris
-
Contact:
- Sonia ALAMOWITCH, MD PhD
- Phone Number: + (33)1-49-28-06-51
- Email: sonia.alamowitch@aphp.fr
-
Contact:
- Arsène MEKINIAN, MD PhD
- Phone Number: + (33)01-48-95-0765
- Email: arsene.mekinian@sat.aphp.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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 14 days after starting the corticosteroids
- Signed Informed Consent Form
- Affiliation to social security
Exclusion Criteria:
Exclusion Criteria :
- 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
- 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
- Previous treatment with TCZ
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: tocilizumab 162mg/0.9mL administered subcutaneously (SC) weekly during 24 weeks
Tocilizumab 162mg/0.9mL
administered subcutaneously (SC) weekly during 24 weeks
|
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.
Other Names:
|
Placebo Comparator: placebo administered subcutaneously (SC) weekly during 24 weeks
Placebo administered subcutaneously (SC) weekly during 24 weeks
|
Placebo administered subcutaneously (SC) weekly during 24 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of patients in complete remission of GCA with absence of ischemic stroke recurrence at 24 weeks under tocilizumab.
Time Frame: From date of treatment initiation until 24 weeks.
|
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
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From date of treatment initiation until 24 weeks.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Compare within tocilizumab and placebo groups the percentage of clinical and MRI ischemic stroke recurrence at 24 weeks
Time Frame: at week 4, 12, 24 and 52.
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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
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at week 4, 12, 24 and 52.
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The relapse-free survival
Time Frame: up to 52 weeks
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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
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up to 52 weeks
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Compare within tocilizumab and placebo groups the time to remission in patients with GCA during 52 weeks.
Time Frame: at week 4, 12, 24 and 52.
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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.
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at week 4, 12, 24 and 52.
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Compare within tocilizumab and placebo groups the improvement of neurovascular radiological involvement during 52 weeks
Time Frame: at week 4, 12, 24 and 52.
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Proportion of patient with neurovascular radiological involvement defined as angio-CT improvement of vasculitis lesions and /or improvement or disappearance of PET FDG uptake.
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at week 4, 12, 24 and 52.
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Compare within tocilizumab and placebo groups the steroid sparing effect at 24 weeks
Time Frame: up to 24 weeks
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Cumulative steroid dose at 24 weeks
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up to 24 weeks
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Mortality at week 4, 12, 24 and 52
Time Frame: at week 4, 12, 24 and 52
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Percentages of deaths at week 4, 12, 24 and 52.
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at week 4, 12, 24 and 52
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Evolution of degree of disability or dependence at week 4, 12, 24 and 52
Time Frame: at week 4, 12, 24 and 52.
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Percentages of patients with rankin score 0-1
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at week 4, 12, 24 and 52.
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Percentage of Participants with Adverse Events/ serious adverse events
Time Frame: at week 4, 12, 24 and 52.
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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
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at week 4, 12, 24 and 52.
|
Collaborators and Investigators
Investigators
- Principal Investigator: Sonia ALAMOWITCH, PU-PH, Assistance Publique - Hôpitaux de Paris
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Skin Diseases
- Immune System Diseases
- Autoimmune Diseases of the Nervous System
- Autoimmune Diseases
- Musculoskeletal Diseases
- Rheumatic Diseases
- Connective Tissue Diseases
- Muscular Diseases
- Vasculitis
- Skin Diseases, Vascular
- Vasculitis, Central Nervous System
- Polymyalgia Rheumatica
- Giant Cell Arteritis
- Arteritis
Other Study ID Numbers
- APHP191062
- 2020-000080-23 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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