Efficacy of Tocilizumab for the Treatment of Acute AION Related to GCA

NCT04239196 | Unknown Phase 2 DMC

• 2 other identifiers: P17-032019-001145-40
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

Giant Cell Arteritis; Optic Ischaemic Neuropathy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Decrease of vision

  Week 8

• Occurrence of a visual improvement

  Week 4 and Week 13

• Change in Mean Deviation

  weeks 4, 8, and 13

• Changes in angio-OCT

  Week 0 and Week 4

• improvement of other manifestations of GCA

  weeks 4, 8, and 13

Study Arms (2)

tocilizumab and IV steroids combination

EXPERIMENTAL

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).

Drug: tocilizumab and IV steroids combination

IV steroids combination alone

OTHER

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.

Other: IV steroids combination alone

Interventions

tocilizumab and IV steroids combination DRUG

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).

tocilizumab and IV steroids combination

IV steroids combination alone OTHER

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.

IV steroids combination alone

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 50 years or older
• Social insurance
• Diagnosis of AION, characterized by sudden and painless loss of vision, of less than one week, accompanied by pallid swelling of the optic disc
• Sudden permanent visual loss due to AION, of less than one week
• 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.

You may not qualify if:

• 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.
• 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
• Contraindication to and precaution in use of tocilizumab according to the summary product description
• Inability to provide informed consent

Sponsors & Collaborators

• Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts: lead
• Roche Chugai: collaborator

Study Sites (10)

CHU de Caen - Hôpital de la Côte de Nacre

Caen, 14033, France

ACTIVE NOT RECRUITING

Hôpital François Mitterrand

Dijon, 21000, France

RECRUITING

CHU de Limoges

Limoges, 87042, France

ACTIVE NOT RECRUITING

CH Montfermeil

Montfermeil, 93370, France

ACTIVE NOT RECRUITING

Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

Paris, 75012, France

RECRUITING

Saint-Antoine Hospital

Paris, 75012, France

RECRUITING

Pitié-Salpetrière Hospital

Paris, 75013, France

ACTIVE NOT RECRUITING

Cochin Hospital

Paris, 75014, France

RECRUITING

Fondation Rothschild,

Paris, 75019, France

RECRUITING

Groupe Hospitalier Diaconesses-Croix Saint Simon,

Paris, 75020, France

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Giant Cell Arteritis; Optic Neuropathy, Ischemic

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases

Study Officials

• Emmanuel Heron, MD

  Centre Hospitalier National d'Ophtalmologie des Quinze-Vints

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tania RILCY

CONTACT

+33 140021126; trilcy@15-20.fr

Hayet SERHANE

CONTACT

+33 140021144; hserhane@15-20.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: optimal Simon two-stage design

Study Record Dates

• First Submitted: November 19, 2019
• First Posted: January 23, 2020
• Study Start: September 10, 2020
• Primary Completion: November 9, 2020
• Study Completion: December 10, 2022
• Last Updated: March 18, 2022

Record last verified: 2022-03

Locations

FR (10)