Giant Cell Arteritis Clinical Trial
— TOCIAIONOfficial title:
Open Label Phase II Randomized Non-comparative Study of SC Tocilizumab Associated With IV Pulse Steroid Versus IV Pulse Steroid Alone for the Treatment of Acute Anterior Ischemic Optic Neuropathy Associated With Giant Cell Arteritis
AION is the main cause of blindness in patients with GCA. High dose steroid is the reference treatment of this condition, but medical unmet need remains. Subcutaneous tocilizumab, a targeted biotherapy, recently received marketing authorization for the treatment of GCA, but only demonstrated at yet that it can allow steroid dose sparing. The aim of this study is to assess the benefit of tocilizumab and IV steroids combination or IV steroids alone, in the treatment of AION due to GCA.
Status | Recruiting |
Enrollment | 58 |
Est. completion date | December 10, 2022 |
Est. primary completion date | November 9, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 50 Years and older |
Eligibility | Inclusion Criteria: 1. Age of 50 years or older 2. Social insurance 3. Diagnosis of AION, characterized by sudden and painless loss of vision, of less than one week, accompanied by pallid swelling of the optic disc 4. Sudden permanent visual loss due to AION, of less than one week 5. Diagnosis of GCA based on the 1st (age = 50 years) and the 3rd (Diagnosis of AION) criteria and at least one among the following : - One unequivocal symptom among: New onset localized headache, scalp or temporal artery tenderness, otherwise unexplained mouth or jaw pain under mastication, or unequivocal symptoms of polymyalgia rheumatic (shoulder and/or hip girdle pain associated with inflammatory stiffness). - Elevated erythrocyte sedimentation rate (= 50 at 1 hour) or C-reactive protein (= 10 mg/l), otherwise unexplained - Abnormal artery biopsy Biopsy specimen with artery showing vasculitis characterized by a predominance of mononuclear cell infiltration or granulomatous inflammation, usually with multinucleated giant cells. - Evidence of large or medium-size vessel vasculitis at ultrasound, magnetic resonance angiography, computed tomography angiography, or positron emission tomography-computed tomography. Exclusion Criteria: - Other ocular involvements related to GCA (central retinal artery occlusion, posterior ischemic optic neuropathy, transient ocular manifestations, occipital stroke), if not associated with AION - Biological targeting therapy within 3 months preceding the study - Evidence of active infection - History of any malignant neoplasm except adequately treated basal or squamous cell carcinoma of the skin or solid tumors treated with curative therapy and disease-free for at least 5 years - History of recurrent infections, diverticulitis or intestinal ulceration and ASAT/ALAT > 5 * upper limit of normal, according to the Summary of Product Characteristics of tocilizumab - Contraindication to steroids and/or aspirin administrated in the treatment - Breastfeeding women and women with childbearing potential without highly effective contraception. - Pregnant or nursing (lactating) women confirmed by a positive ßHCG laboratory test at the inclusion - Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during study treatment and for 3 months after the last administration of tocilizumab. - Cytopenia, as defined by platelet count < 100 × 109/L (100,000/mm3), hemoglobin < 85 g/L (8.5 g/dL; 5.3 mmol/L), absolute neutrophil count < 2.0 × 109/L (2000/mm3), absolute lymphocyte count < 0.5 × 109/L (500/mm3) - Insufficient liver function (Child Pugh C ) - Insufficient kidney function, as defined by a serum creatinine of more than 3 mg/dL or creatinine clearance of 20 ml/min or less - Patients with previously untreated tuberculosis, previously known TDM/radiographic evidence suggestive of active and/or sequellar tuberculosis - HIV infected, hepatitis C infected, or a positive hepatitis B surface antigen if known before study inclusion - Contraindication to and precaution in use of tocilizumab according to the summary product description - Inability to provide informed consent |
Country | Name | City | State |
---|---|---|---|
France | CHU de Caen - Hôpital de la Côte de Nacre | Caen | |
France | Hôpital François Mitterrand | Dijon | |
France | CHU de Limoges | Limoges | |
France | CH Montfermeil | Montfermeil | |
France | Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts | Paris | |
France | Cochin Hospital | Paris | |
France | Fondation Rothschild, | Paris | |
France | Groupe Hospitalier Diaconesses-Croix Saint Simon, | Paris | |
France | Pitié-Salpetrière Hospital | Paris | |
France | Saint-Antoine Hospital | Paris |
Lead Sponsor | Collaborator |
---|---|
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts | Roche Chugai |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | ocular change | The primary endpoint will be the ocular change at Week 8. This change will be defined as the increase of at least two lines of visual acuity on the ETDRS chart. | Week 8 | |
Secondary | Decrease of vision | Stabilization of vision, as judged at Week 8 after treatment start, correspond to a lack of deterioration :
If the patient can see the light initially, no light perception at W8 will represent a deterioration If the patient is able to count finger at any distance, but the visual acuity is less than 20/400 on the ETRS chart, a "off chart" visual acuity at W8 will represent a deterioration If initial visual acuity is equal or more than 20/400, a loss of 2 lines or more on the ETDRS at Week 8 will represent deterioration |
Week 8 | |
Secondary | Occurrence of a visual improvement | Occurrence of a visual improvement defined as an increase of two lines or more of visual acuity on ETDRS chart, a clinically significant difference, at Week 4 and Week 13 | Week 4 and Week 13 | |
Secondary | Change in Mean Deviation | Change in Mean Deviation (MD) measured on an automatized Visual Field (SITA Standard Humphrey 24-2) at weeks 4, 8, and 13 | weeks 4, 8, and 13 | |
Secondary | Changes in angio-OCT | Changes in angio-OCT between baseline and Week 4 : superficial and deep vascular plexus will be examined to look for the decrease of ischemia in peripapillary and macular areas. | Week 0 and Week 4 | |
Secondary | improvement of other manifestations of GCA | Proportion of patients with improvement of other manifestations of GCA with tocilizumab and prednisone at weeks 4, 8, and 13 | weeks 4, 8, and 13 | |
Secondary | biological improvement | Proportion of patients with biological improvement (i.e. CRP and ESR) with tocilizumab and prednisone at weeks 4, 8, and 13 | weeks 4, 8, and 13 | |
Secondary | recurrence of AION | Influence of 1-month tocilizumab treatment on recurrence of AION, at W13. | week 13 | |
Secondary | recurrence of GCA | Influence of 1-month tocilizumab treatment on recurrence of GCA, at Week 13. | Week 13 | |
Secondary | first recurrence of GCA | Time to first recurrence of GCA | weeks 1, 2, 3, 4, 8 and 13 | |
Secondary | Immunological biomarkers | Immunological biomarkers of response to Tocilizumab assessed at W0, W4, and W13. | weeks 0,4 and 13 |
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