"Comparison of the Efficacy and Safety of Adalimumab to That of Tocilizumab in Severe Uveitis of Behçet's Disease"

NCT05874505 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: APHP200007
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

UVB, is the first randomized prospective, head to head study, comparing Adalimumab to Tocilizumab in sight threatening uveitis of Behçet's Disease (BD). Anti-TNFα has been used for BD uveitis for 15 years. The incidence of blindness in BD has been dramatically reduced in the recent years with the use of biologics. There is no firm evidence or randomized controlled trials directly addressing the best induction therapy in severe BD uveitis. BD uveitis is considered as the most devastating inflammatory ocular disease. Risk of visual loss reaches 25% at 5 years and 80% of patients have a bilateral involvement. Contrasting with immunosuppressors or interferon-alpha, biotherapies act rapidly and are highly effective in steroid's sparing thus preventing occurrence of cataract and/or glaucoma. However, anti-TNFα failed to demonstrate sustainable complete remission over 50 % of severe sight threatening uveitis. There is little published information on use of biologics other than anti-TNFα for severe BD uveitis. Tocilizumab has been used with success in severe and/or resistant cases and is one of the most promising biologics in BD. IL-6 expression correlates with BD activity and other immunological data provide a strong rationale for targeting BD with tocilizumab. Despite a strong rationale, these compounds are not yet approved in BD, which guarantees the innovative nature of this study that aims selecting or dropping any arm when evidence of efficacy already exists. The objective of the study is to assess the benefit of tocilizumab comparatively to that of adalimumab in sight-threatening Behçet's disease uveitis at week 16

Conditions

Behcet's Uveitis

Keywords

Biologics; Adalimumab; Tocilizumab

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with complete remission of ocular involvement (Efficacy)

  Efficacy will be defined by a complete remission of ocular involvement with prednisone lower or equal to 5 mg/day . Ocular involvement response to treatment will be evaluated according to the Standardization of Uveitis Nomenclature (SUN) Workgroup criteria.

  At week 16 after randomization

Secondary Outcomes (85)

• Percent of patients meeting the corticosteroid sparing targets

  At week 16 after randomization

• Mean dose of corticosteroids

  At week 16 after randomization

• Cumulative dose of corticosteroids

  At week 16 after randomization

• Time to response onset

  Up to week 48

• Erythrocyte sedimentation rate

  At week 4

Study Arms (2)

Adalimumab

EXPERIMENTAL

Adalimumab 80 mg at Day 0 then 40 mg subcutaneous at week 1, 3, 5, 7, 9, 11, 13 and 15

Drug: Adalimumab

Tocilizumab

EXPERIMENTAL

Tocilizumab 162 mg subcutaneous each week for 15 weeks

Drug: Tocilizumab

Interventions

Adalimumab DRUG

Adalimumab 80 mg at Day 0 then 40 mg subcutaneous at week 1, 3, 5, 7, 9, 11, 13 and 15

Adalimumab

Tocilizumab DRUG

Tocilizumab 162 mg subcutaneous each week for 15 weeks

Tocilizumab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written, informed consent prior to the performance of any study-specific procedures
• Diagnosis of Behçet's disease according to the International Criteria for Behçet's Disease (ICBD) or history of aphthosis.
• 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
• 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).
• For female subjects of childbearing potential (premenopausal female capable of becoming pregnant) , a negative serum pregnancy test (plasmatic or urinary)
• 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. Birth control methods which may be considered as highly effective methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods (according to CTFG recommendations). Such methods include:
• combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• oral
• intravaginal
• transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation:
• oral
• injectable
• implantable
• intrauterine device (IUD)

You may not qualify if:

• Infectious uveitis, masquerade syndromes, or uveitis due to causes other than BD uveitis
• Active tuberculosis or history of untreated tuberculosis and/or severe infection
• History of severe allergic or anaphylactic reactions to monoclonal antibodies
• History of multiple sclerosis and/or demyelinating disorder
• Hypersensitivity to the active substance or an excipient of the Investigational Medicinal Product or the auxiliary medicine
• Active or suspected ocular infection
• Active or suspected systemic infection
• History of intestinal ulceration or diverticulitis
• Known porphyria
• Neutrophil \< 1.0 x 10\^3 /mm3
• Platelet count \< 80 x 10\^3 /mm3
• ASAT or ALAT \> 5 ULN
• Stage III and IV New York Heart Association (NYHA) cardiac insufficiency
• Severe renal (Glomerular filtration rates (GFR) \<30ml/min) or liver insufficiency (prothrombin \<50% without other causes)
• Breastfeeding or pregnant women

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Interventions

Adalimumab; tocilizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Bahram BODAGHI, Pr

CONTACT

+33 1 42 16 37 28; bahram.bodaghi@aphp.fr

Matthieu RESCHE-RIGON, Pr

CONTACT

+33 1 42 49 97 42; matthieu.resche-rigon@u-paris.fr

Study Design

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

Study Record Dates

• First Submitted: April 14, 2023
• First Posted: May 25, 2023
• Study Start: July 1, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: May 25, 2023

Record last verified: 2023-04