Efficacy of tocilizumab in the treatment of acute anterior ischemic optic neuropathy optic neuropathy in Horton's disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier National D'Ophtalmologie Quinze-Vingts

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11], Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

27 Jan 2025 → 24 Sep 2025

Decision date (initial)

2025-01-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ROCHE CHUGAI

External identifiers

EU CT number

2024-519977-20-00

EudraCT number

2019-001145-40

ClinicalTrials.gov

NCT04239196

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To determine if induction therapy by 4 subcutaneous tocilizumab injections over one month (every 7 days) in association to conventional steroid regimen could improve ocular outcome in acute anterior ischemic optic neuropathy (AION) related to Giant Cell Arteritis (GCA)

Secondary objectives 9

1. To determine if induction therapy by 4 subcutaneous tocilizumab injections over one month (every 7 days) in association to conventional steroid regimen could stabilize visual outcome in AION related to GCA
2. Visual stabilization will be judged at W8 after treatment start as an absence of visual improvement and of visual deterioration
3. To assess the efficacy of 1-month tocilizumab treatment on the other manifestations of GCA
4. W4 and W13 occurrence of an increase of two lines or more of visual acuity on the ETDRS chart
5. Change in Mean Deviation (MD) measured on an automatized Visual Field ( SITA Standard Humphrey 24-2) at W4, W8 and W13
6. 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.
7. To assess the recurrence rate at W13
8. To assess the safety
9. To determine immunological biomarkers predictive of the response to tocilizumab

Conditions and MedDRA coding

Acute Anterior Ischemic Optic Neuropathy associated with Giant Cell Arteritis in Horton's Disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Diagnosis of GCA (Giant Cell Arteritis)
2. AION characterized by sudden and painless loss of vision, accompanied by pallid swelling of the optic disc, of no more than one-week duration
3. Age of 50 years or older
4. Social insurance

Exclusion criteria 16

1. Other ocular involvements related to GCA (central retinal artery occlusion, posterior ischemic optic neuropathy, transient ocular manifestations, occipital stroke), if not associated with AION
2. Biological targeting therapy within 3 months preceding the study
3. Evidence of active infection
4. 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
5. 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
6. Contraindication to steroids and/or aspirin administrated in the treatment
7. Breastfeeding women and women with childbearing potential without highly effective contraception.
8. Pregnant or nursing (lactating) women confirmed by a positive βHCG laboratory test at the inclusion
9. 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.
10. 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)
11. Insufficient liver function (Child Pugh C )
12. Insufficient kidney function, as defined by a serum creatinine of more than 3 mg/dL or creatinine clearance of 20 ml/min or less
13. Patients with previously untreated tuberculosis, or imaging data suggestive of active and/or sequellar tuberculosis
14. HIV infected, hepatitis C infected, or a positive hepatitis B surface antigen if known before study inclusion
15. Contraindication to and precaution in use of tocilizumab according to the summary product description
16. Inability to provide informed consent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 11

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.
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: 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 4, 8, and 13.
6. Proportion of patients with biological improvement (i.e. CRP and ESR) with tocilizumab and prednisone at weeks 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 W0, W4, and W13.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier National D'Ophtalmologie Quinze-Vingts

Sponsor organisation

Centre Hospitalier National D'Ophtalmologie Quinze-Vingts

Address

28 Rue De Charenton

City

Paris

Postcode

75012

Country

France

Scientific contact point

Organisation

Centre Hospitalier National D'Ophtalmologie Quinze-Vingts

Contact name

Project Manager

Public contact point

Organisation

Centre Hospitalier National D'Ophtalmologie Quinze-Vingts

Contact name

Project Manager

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications