Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04239196
Other study ID # P17-03
Secondary ID 2019-001145-40
Status Recruiting
Phase Phase 2
First received
Last updated
Start date September 10, 2020
Est. completion date December 10, 2022

Study information

Verified date March 2022
Source Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Contact Tania RILCY
Phone +33 140021126
Email trilcy@15-20.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

Tocilizumab will be proposed to eligible patients as an emergency treatment, in addition to the standard high-dose steroid treatment. Each patient will receive the reference treatment, i.e. one pulse of high dose intravenous methylprednisolone per day during 3 days, followed by 1 mg/kg/day oral prednisone, and low dose aspirin. Depending on the randomization, each patient will receive the reference treatment only, or will received in addition to the reference treatment four subcutaneous injections of tocilizumab 162 mg over one month (1 injection per week), the first tocilizumab injection being delivered on the same day than the first steroid IV pulse. Study visits will take place at 4, 8 and 13 weeks. The primary endpoint will be the ocular improvement at W8, defined as an increase of at least two lines of visual acuity on the ETRS chart. For each patient, the duration of participation will by of 3 months. The study duration is expected to be 15 months.


Recruitment information / eligibility

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

Study Design


Intervention

Drug:
tocilizumab and IV steroids combination
Every patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months. Patients will receive in addition to the reference treatment four subcutaneous injections of tocilizumab 162 mg over one month (1 injection per week).
Other:
IV steroids combination alone
Every patient will receive the reference treatment for GCA with ocular complication, i.e. high dose corticosteroid therapy (intravenous pulses of 7,5 to 15 mg/kg/day of methylprednisolone with an upper limit of 1000 mg/day for 3 days followed by oral prednisone at 1 mg/kg/day with progressive decrease as usually done) and aspirin 75 mg/day. The mean duration of this reference treatment is 18 months.

Locations

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

Sponsors (2)

Lead Sponsor Collaborator
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts Roche Chugai

Country where clinical trial is conducted

France, 

Outcome

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
See also
  Status Clinical Trial Phase
Completed NCT03812302 - Use of Gallium-68 HA-DOTATATE PET/CT in Giant Cell Arteritis (GCA) Phase 2
Recruiting NCT02257866 - Studies of the Natural History, Pathogenesis, and Outcome of Idiopathic Systemic Vasculitis
Recruiting NCT04888221 - Efficacy of Tocilizumab in Association to Steroids in Giant Cell Arteritis With Cerebro-vascular Involvement Phase 3
Recruiting NCT05380453 - Efficacy and Safety of Secukinumab in Patients With New Onset of Giant Cell Arteritis Who Are in Clinical Remission Phase 3
Recruiting NCT02333708 - Study of Circulating Microparticles in Giant Cell Arteritis
Completed NCT01450137 - Tocilizumab for Patients With Giant Cell Arteritis Phase 2
Completed NCT03827018 - KPL-301 for Subjects With Giant Cell Arteritis Phase 2
Active, not recruiting NCT04519580 - Improved Diagnostics and Monitoring of Polymyalgia Rheumatica
Recruiting NCT06460142 - Assessing Biomarker in Giant Cell Arteritis and Polymyalgia Rheumatic
Completed NCT03202368 - An Extension Study to Evaluate Long-Term Safety of Subcutaneous (SC) Tocilizumab in Participants With Giant Cell Arteritis (GCA) Phase 3
Not yet recruiting NCT02523625 - Giant Cell Arteritis: Improving Use of Ultrasound Evaluation N/A
Completed NCT03285945 - FDG Uptake in Large-Vessel Giant Cell Arteritis After Short-term, High-Dose Steroid Treatment N/A
Completed NCT02190916 - Vasculitis Illness Perception (VIP) Study N/A
Recruiting NCT01241305 - One-Time DNA Study for Vasculitis
Terminated NCT02531633 - Efficacy and Safety Study of Sirukumab in Patients With Giant Cell Arteritis Phase 3
Completed NCT03409913 - Diagnostic Accuracy of FDG PET/CT of Cranial Arteries in GCA N/A
Completed NCT03765424 - Evaluation of Ultrasound and PET/CT in the Diagnosis and Monitoring of Giant Cell Arteritis
Completed NCT01910038 - Evaluation of Tocilizumab as an add-on Therapy to Corticoids in Giant Cell Arteritis: Proof of Concept Study. Phase 2
Not yet recruiting NCT04012905 - Giant Cell Arteritis: Comparison Between Two Standardized Corticosteroids Tapering Phase 3
Recruiting NCT06004154 - Post-therapeutic Imaging Evaluation of Patients With Horton's Disease (Giant Cell Arteritis) (EvHortim)