Clinical trial NCT05874505: "Comparison of the Efficacy and Safety of Adalimumab to That of Tocilizumab in Severe Uveitis of Behçet's Disease"
Official title: "Multicenter, Randomized, Prospective Trial Comparing the Efficacy and Safety of Adalimumab to That of Tocilizumab in Severe Uveitis of Behçet's Disease" (UVB) : Treatment of UVeitis in Behçet's Diseases With Biologics
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Behcet's Uveitis
Keywords: Biologics
Adalimumab
Tocilizumab
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2023-05-25
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

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) or history of aphthosis.
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 childbearing 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. 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)
   * intrauterine hormone-releasing system (IUS)
   * bilateral tubal occlusion
   * vasectomised partner
   * sexual abstinence (In the context of this guidance sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject).

   For male subjects :
   * use of a condom
   * vasectomy (with documentation of azoospermia)
   * sexual abstinence
9. A potential subject with a positive interferon-gamma release assay (IGRA) (e.g., QuantiFERON®-TB Gold or T-spot TB® Test) obtained within 6 months prior to inclusion 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 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:

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 or adequately treated, 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 Investigational Medicinal Product or the auxiliary medicine
8. Active or suspected ocular infection
9. Active or suspected systemic infection
10. History of intestinal ulceration or diverticulitis
11. Known porphyria
12. Laboratory values assessed during Inclusion:

    1. Neutrophil \< 1.0 x 10\^3 /mm3
    2. Platelet count \< 80 x 10\^3 /mm3
    3. ASAT or ALAT \> 5 ULN
13. Treatment with anti-TNF and/or Tocilizumab therapy within 1 month prior to inclusion
14. if 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 4 weeks prior to inclusion
18. Breastfeeding or pregnant women

Primary outcomes:
measure: Proportion of patients with complete remission of ocular involvement (Efficacy)
timeFrame: At week 16 after randomization
Secondary outcomes:
measure: Percent of patients meeting the corticosteroid sparing targets
timeFrame: At week 16 after randomization
measure: Mean dose of corticosteroids
timeFrame: At week 16 after randomization
measure: Cumulative dose of corticosteroids
timeFrame: At week 16 after randomization
measure: Time to response onset
timeFrame: Up to week 48
measure: Erythrocyte sedimentation rate
timeFrame: At week 4
measure: Erythrocyte sedimentation rate
timeFrame: At week 8
measure: Erythrocyte sedimentation rate
timeFrame: At week 12
measure: Erythrocyte sedimentation rate
timeFrame: At week 16
measure: Erythrocyte sedimentation rate
timeFrame: At week 24
measure: Erythrocyte sedimentation rate
timeFrame: At week 36
measure: Erythrocyte sedimentation rate
timeFrame: At week 48
measure: C-reactive protein rate
timeFrame: At week 4
measure: C-reactive protein rate
timeFrame: At week 8
measure: C-reactive protein rate
timeFrame: At week 12
measure: C-reactive protein rate
timeFrame: At week 16
measure: C-reactive protein rate
timeFrame: At week 24
measure: C-reactive protein rate
timeFrame: At week 36
measure: C-reactive protein rate
timeFrame: At week 48
measure: Rate of relapses
timeFrame: up to 48 weeks
measure: Time to occurrence of relapse or worsening of uveitis
timeFrame: up to 48 weeks
measure: Disease activity assessed by Behcet's Disease Current Activity
timeFrame: At week 8
measure: Disease activity assessed by Behcet's Disease Current Activity
timeFrame: At week 16
measure: Disease activity assessed by Behcet's Disease Current Activity
timeFrame: At week 24
measure: Disease activity assessed by Behcet's Syndrome Activity Score
timeFrame: At week 8
measure: Disease activity assessed by Behcet's Syndrome Activity Score
timeFrame: At week 16
measure: Disease activity assessed by Behcet's Syndrome Activity Score
timeFrame: week 24
measure: Changes in the number of other organs involved by Behcet Disease (BD)
timeFrame: At week 4
measure: Changes in the number of other organs involved by Behcet Disease (BD)
timeFrame: At week 8
measure: Changes in the number of other organs involved by Behcet Disease (BD)
timeFrame: At week 12
measure: Changes in the number of other organs involved by Behcet Disease (BD)
timeFrame: At week 16
measure: Changes in the number of other organs involved by Behcet Disease (BD)
timeFrame: At week 24
measure: Changes in the number of other organs involved by Behcet Disease (BD)
timeFrame: At week 36
measure: Changes in the number of other organs involved by Behcet Disease (BD)
timeFrame: At week 48
measure: Quality of Life assessed by Behcet's Disease Quality of Life Measure
timeFrame: At week 16
measure: Quality of Life assessed by Behcet's Disease Quality of Life Measure
timeFrame: At week 24
measure: Changes in Short Form (36) Health Survey for quality of life
timeFrame: At week 16
measure: Changes in Short Form (36) Health Survey for quality of life
timeFrame: At week 24
measure: Proportion of patients with adverse clinical events
timeFrame: at week 4
measure: Proportion of patients with adverse clinical events
timeFrame: at week 8
measure: Proportion of patients with adverse clinical events
timeFrame: at week 12
measure: Proportion of patients with adverse clinical events
timeFrame: at week 16
measure: Proportion of patients with adverse clinical events
timeFrame: at week 24
measure: Proportion of patients with adverse clinical events
timeFrame: at week 36
measure: Proportion of patients with adverse clinical events
timeFrame: at week 48
measure: Severity of adverse clinical events
timeFrame: At week 4
measure: Severity of adverse clinical events
timeFrame: At week 8
measure: Severity of adverse clinical events
timeFrame: At week 12
measure: Severity of adverse clinical events
timeFrame: At week 16
measure: Severity of adverse clinical events
timeFrame: At week 24
measure: Severity of adverse clinical events
timeFrame: At week 36
measure: Severity of adverse clinical events
timeFrame: At week 48
measure: Changes in Tyndall score
timeFrame: At week 8
measure: Changes in Tyndall score
timeFrame: At week 16
measure: Changes in Tyndall score
timeFrame: At week 24
measure: Changes in Tyndall score
timeFrame: At week 36
measure: Changes in Tyndall score
timeFrame: At week 48
measure: Changes in flare score
timeFrame: At week 8
measure: Changes in flare score
timeFrame: At week 16
measure: Changes in flare score
timeFrame: At week 24
measure: Changes in flare score
timeFrame: At week 36
measure: Changes in flare score
timeFrame: At week 48
measure: Changes of Vitreous Haze
timeFrame: At week 8
measure: Changes of Vitreous Haze
timeFrame: At week 16
measure: Changes of Vitreous Haze
timeFrame: At week 24
measure: Changes of Vitreous Haze
timeFrame: At week 36
measure: Changes of Vitreous Haze
timeFrame: At week 48
measure: Changes in Best corrected visual acuity
timeFrame: At week 8
measure: Changes in Best corrected visual acuity
timeFrame: At week 16
measure: Changes in Best corrected visual acuity
timeFrame: At week 24
measure: Changes in Best corrected visual acuity
timeFrame: At week 36
measure: Changes in Best corrected visual acuity
timeFrame: At week 48
measure: Changes in central retinal thickness
timeFrame: At week 8
measure: Changes in central retinal thickness
timeFrame: At week 16
measure: Changes in central retinal thickness
timeFrame: At week 24
measure: Changes in central retinal thickness
timeFrame: At week 36
measure: Changes in central retinal thickness
timeFrame: At week 48
measure: Percentage of patients with central retinal thickness <300 microns
timeFrame: At week 8
measure: Percentage of patients with central retinal thickness <300 microns
timeFrame: At week 16
measure: Percentage of patients with central retinal thickness <300 microns
timeFrame: At week 24
measure: Percentage of patients with central retinal thickness <300 microns
timeFrame: At week 36
measure: Percentage of patients with central retinal thickness <300 microns
timeFrame: At week 48
measure: Percentage of patients without retinal vessel leakage on retinal angiography
timeFrame: At week 16
measure: Percentage of patients without retinal vessel leakage on retinal angiography
timeFrame: At week 24
measure: Percentage of patients without retinal vessel leakage on retinal angiography
timeFrame: At week 36
measure: Percentage of patients without retinal vessel leakage on retinal angiography
timeFrame: At week 48
Other outcomes:
Locations:
Study officials:
References: