UVB: treatment of UVeitis in Behçet’s diseases with biologic

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

25 Apr 2024 → ongoing

Decision date (initial)

2024-08-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PHRC National 2019 - Ministère des solidarités et de la Santé

External identifiers

EU CT number

2024-513371-41-00

EudraCT number

2022-001316-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To assess the benefit of tocilizumab comparatively to that of adalimumab in sight-threatening Behçet’s disease uveitis at week 16.

Secondary objectives 13

1. To estimate and compare the change in best corrected visual acuity (BCVA)
2. Time to complete remission at week 4, 8, 12, 24, 36 and 48
3. To evaluate and compare the safety of Adalimumab and tocilizumab
4. To evaluate and compare the change in macular edema
5. To evaluate and compare the change in other signs of ocular inflammation
6. To evaluate and compare the effect on retinal vessel leakage
7. To evaluate and compare the effect of Adalimumab and tocilizumab on steroid sparing
8. To evaluate and compare the change in ocular inflammation in the anterior chamber
9. To evaluate and compare the number and time to relapse of uveitis and the characteristics of uveitis at worsening
10. To evaluate and compare the time to treatment failure (Patients will be considered to have treatment failure if any of the following criteria is met in at least 1 eye: new active, inflammatory retinal vascular lesions and/or macular edema; worsening best corrected visual acuity (BCVA) by ≥3 lines; 2-step increase in anterior chamber (AC) cell grade; 2-step increase in vitreous haze (VH) grade relative to Baseline)
11. To estimate and compare the effect on extra ophthalmologic manifestations of Behçet’s Disease
12. To estimate and compare the mean change in SF-36 quality of life and Behçet’s Disease Quality of Life Measure
13. To estimate and compare the changes in Behcet’s Disease Current Activity Form and Behcet’s Syndrome Activity Score

Conditions and MedDRA coding

Severe uveitis of Behçet’s disease

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Age >= 18 at Inclusion
2. Provide written, informed consent prior to the performance of any study-specific procedures
3. Diagnosis of Behçet’s disease according to the International Criteria for Behçet's Disease (ICBD) (see appendix 18.2) or history of aphtosis
4. Diagnosis of non-infectious intermediate, posterior-, or pan-uveitis in at least one eye fulfilling the International Study Group Classification Criteria (Standardization of Uveitis Nomenclature [SUN] criteria) of posterior, or pan- uveitis
5. Sight threatening uveitis defined according to the validated international definition as 2 lines of drop in visual acuity on a 10/10 scale, and/or retinal inflammation (macular oedema and/or retinal vasculitis).
6. Chest X-ray (postero-anterior and lateral) or CT-scanner results within 12 weeks prior to Inclusion with no evidence of active Tuberculosis, active infection, or malignancy
7. For female subjects of child-bearing potential (premenopausal female capable of becoming pregnant), a negative serum pregnancy test (plasmatic or urinary)
8. For subjects with reproductive potential, a willingness to use contraceptive measures adequate to prevent the subject or the subject’s partner from becoming pregnant during the study and 3 and 5 months after stopping therapy for tocilizumab and adalimumab, respectively.
9. Negative TB test obtained within 12 weeks prior to inclusion. A potential subject with a positive interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test) is eligible if her/his chest X-ray does not show evidence suggestive of active TB disease and there are no clinical signs and symptoms of pulmonary and/or UVB protocol, version 5.0 of 02/04/2024 31/76 This document is the property of DRCI/AP-HP. All reproduction is strictly prohibited extra-pulmonary TB disease. These subjects with a latent TB infection who have not already received a prophylactic TB treatment must agree in advance to complete such a treatment course. The treatment should be started at the latest at inclusion
10. Affiliation to a social security system. Patients affiliated to universal medical coverage (CMU) are eligible for the study

Exclusion criteria 18

1. Infectious uveitis, masquerade syndromes, or uveitis due to causes other than BD uveitis
2. Active tuberculosis or history of untreated tuberculosis and/or severe infection
3. Positive HIV antibody and/or positive hepatitis B surface antigen and/or positive hepatitis C RNA, results obtained within 1 month prior to inclusion
4. History of malignancy within 5 years prior to Inclusion other than carcinoma in situ of the cervix, non-metastatic squamous or basal cell carcinoma of the skin
5. History of severe allergic or anaphylactic reactions to monoclonal antibodies
6. History of multiple sclerosis and/or demyelinating disorder
7. Hypersensitivity to the active substance or an excipient of the IMP or the auxiliary medicine
8. Active or suspected ocular infection
9. Infection oculaire active suspectée
10. History of intestinal ulceration or diverticulitis
11. Known porphyria
12. Laboratory values assessed during Inclusion: a. Neutrophil < 1.0 x 10^3/mm3 ; b. Platelet count < 80x 10^3/mm3 ; c. ASAT or ALAT > 5 ULN
13. Treatment with anti-TNF and/or Tocilizumab therapy within 1 month prior to inclusion
14. Patient on azathioprine, mycophenolate mofetil, or methotrexate at the time of inclusion (these drugs must be withdrawn prior to receiving the tocilizumab or adalimumab dose on Day 0).
15. Stage III and IV New York Heart Association (NYHA) cardiac insufficiency
16. Severe renal (Glomerular filtration rates (GFR) <30ml/min) or liver insufficiency (prothrombin <50% without other causes)
17. Any live (attenuated) vaccine within 30 days prior to inclusion
18. Breastfeeding and pregnant women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy will be defined by a complete remission of ocular involvement with prednisone (or prednisolone, only if prednisone is out of stock in the market) lower or equal to 5 mg/day at W16 after randomization. Complete remission of ocular inflammation will be defined as complete resolution of retinal vasculitis and/or macular edema with prednisone (or prednisolone, only if prednisone is out of stock) lower or equal to 5 mg/day at W16. In patients with bilateral uveit

Secondary endpoints 15

1. Measures of corticosteroid sparing (e.g., percent meeting targets [lower than 0.1 mg/day/kg of prednisone (or prednisolone, only if prednisone is out of stock in the market)], mean dose at week 16, and cumulative dose).
2. Time to response onset
3. Measures of acute-phase reactants (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], at week 4, 8, 12, 16, 24, 36 and 48
4. Rate and Time to occurrence of relapse or worsening while on study. (Relapse will be defined as the reappearance of clinical and/or paraclinical features of active disease or by the occurrence of new lesions or progression of preexisting lesions).
5. Changes in Behcet’s Disease Current Activity Form (BDCA) at week 8, 16 and 24
6. Changes in Behcet’s Syndrome Activity Score (BSAS) at week 16
7. Changes in other organs involved by BD at week 4, 8, 12, 16, 24, 36 and 48
8. Changes in quality of life (QOL) (SF36v2 TM Health Survey) and Behcet’s Disease Quality of Life Measure (BD-QoL) at week 16 and 24
9. Safety and tolerability of treatments in BD patients as assessed by frequency and severity of adverse clinical events at week 4, 8, 12, 16, 24, 36 and 48
10. Time to treatment failure (time to occurence)
11. Changes in Tyndall, flare and Vitreous Haze at week 8, 16, 24, 36 and 48
12. Changes in Best corrected visual acuity (SNELLEN score) at week 8, 16, 24, 36 and 48
13. Changes in central retinal thickness measured with Optical Coherence Tomography (OCT) at week 8, 16, 24, 36 and 48
14. Percentage of patients with central retinal thickness <300 microns at week 8, 16, 24, 36 and 48
15. Percentage of patients without retinal vessel leakage on retinal angiography at week 16, and at week 24, 36 and 48, in case of retinal vasculitis

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Bahram BODAGHI

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Bahram BODAGHI

Locations

1 EU/EEA country · 27 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

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