Giant cell arteritis, acute anterior ischemic optic neuropathy MedDRA version: 21.1 Level: PT Classification code 10043207 Term: Temporal arteritis System Organ Class: 10047065 - Vascular disorders MedDRA version: 20.1 Level: PT Classification code 10030924 Term: Optic ischaemic neuropathy System Organ Class: 10015919 - Eye disorders
Conditions
Interventions
Trade Name: RoActemre
Product Name: Roactemra
Product Code: L04AC07
Pharmaceutical Form: Suspension for injection in pre-filled syringe
Sponsors
Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Diagnosis of GCA : ACR criteria (annex 1) • Sudden permanent visual loss due to AION, of less than one week • Diagnosis of AION, characterized by sudden and painless loss of vision, accompanied by pallid swelling of the optic disc • Age of 50 years or older • Social insurance Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 58 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 58
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluation of the efficacy of a one-month tocilizumab treatment as induction therapy in combination with high dose steroids in patients with anterior ischemic optic neuropathy (AION) due to giant cell arteritis, as judged at W8 after treatment start : Occurrence of a visual improvement defined as an increase of two lines or more of visual acuity on the ETDRS chart;Secondary Objective: • To determine if induction therapy by 4 subcutaneous tocilizumab injections over one month (every 7 days) in association to conventional steroid regimen could stabilize ocular outcome in AION related to GCA. • To assess the efficacy of 1-month, tocilizumab treatment on the other manifestations of GCA (clinical remission, associated rhizomelic polyarthritis) • W4 and W13 Occurrence of a visual improvement defined as an increase of two lines or more of visual acuity on ETDRS chart • W4, W8 and W13 changes in Mean Deviation (MD) measured on an automatized Visual Field ( SITA Standard Humphrey 24-2) • 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. • To assess the recurrence rate at W13 • To determine immunological biomarkers predictive of response to Tocilizumab (ancillary study) • To assess the safety;Primary end point(s): The primary endpoint will be the ocular improvement at W8. This improvement will be defined as the increase of at least two lines of visual acuity on the ETDRS chart. ;Timepoint(s) of evaluation of this end point: W8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1- Stabilization of vision, as judged at W8 after treatment start, correspond to a lack of improvement (cf primary objective), and a lack of deterioration defined as follows: - 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 2- 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 W4 and W13 3- Change in Mean Deviation (MD) measured on an automatized Visual Field (SITA Standard Humphrey 24-2) at weeks 4, 8, and 13. 4- Changes in angio-OCT between baseline and W4 and W13: superficial and deep vascular plexus will be examined to look for the decrease of ischemia in peripapillary and macular areas. 5- Proportion of patients with improvement of other manifestations of GCA with tocilizumab and prednisone at weeks 2, 4, 8, and 13. 6- Proportion of patients with biological improvement (i.e. CRP and ESR) with tocilizumab and prednisone at weeks 2, 4, 8, and 13. 7- Influence of 1-month tocilizumab treatment on recurrence of AION, at W13. 8- Influence of 1-month tocilizumab treatment on recurrence of GCA, at W13. 9- Time to first recurrence of GCA 10- Safety as assessed by adverse events, and serious adverse events. 11- Immunological biomarkers of response to Tocilizumab assessed at W2, W4, W8 and W13. ;Timepoint(s) of evaluation of this end point: 1- at W8 2- at W4 and W13 3- at weeks 4, 8, and 13. 4- between baseline and W4 and W13 5- at weeks 2, 4, 8, and 13. 6- at weeks 2, 4, 8, and 13. 7- at W13. 8- at W13. 9-10 each week 11- at W2, W4, W8 and W13. | — |
Countries
France
Contacts
Public ContactDr Emmanuel Heron
Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts
Outcome results
None listed