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

Behcet's Uveitis Clinical Trial

— UVB  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05874505
• Other study ID #: APHP200007
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2023
• Est. completion date: July 2027

Study information

• Verified date: April 2023
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Bahram BODAGHI, Pr
• Phone: +33 1 42 16 37 28
• Email: bahram.bodaghi[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: July 2027
• Est. primary completion date: November 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Behcet Syndrome
• Behcet's Uveitis
• Uveitis

Intervention

Drug:
• Adalimumab
Adalimumab 80 mg at Day 0 then 40 mg subcutaneous at week 1, 3, 5, 7, 9, 11, 13 and 15
• Tocilizumab
Tocilizumab 162 mg subcutaneous each week for 15 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percent of patients meeting the corticosteroid sparing targets	lower than 0.1 mg/day/kg of prednisone	At week 16 after randomization
Secondary	Mean dose of corticosteroids		At week 16 after randomization
Secondary	Cumulative dose of corticosteroids		At week 16 after randomization
Secondary	Time to response onset		Up to week 48
Secondary	Erythrocyte sedimentation rate		At week 4
Secondary	Erythrocyte sedimentation rate		At week 8
Secondary	Erythrocyte sedimentation rate		At week 12
Secondary	Erythrocyte sedimentation rate		At week 16
Secondary	Erythrocyte sedimentation rate		At week 24
Secondary	Erythrocyte sedimentation rate		At week 36
Secondary	Erythrocyte sedimentation rate		At week 48
Secondary	C-reactive protein rate		At week 4
Secondary	C-reactive protein rate		At week 8
Secondary	C-reactive protein rate		At week 12
Secondary	C-reactive protein rate		At week 16
Secondary	C-reactive protein rate		At week 24
Secondary	C-reactive protein rate		At week 36
Secondary	C-reactive protein rate		At week 48
Secondary	Rate of relapses	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	up to 48 weeks
Secondary	Time to occurrence of relapse or worsening of uveitis	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	up to 48 weeks
Secondary	Disease activity assessed by Behcet's Disease Current Activity	Changes in Behcet's Disease Current Activity Form 2006 The score varies between 0 and 12, the higher the score the higher the disease activity.; Lawton G, Bhakta BB, Chamberlain MA, Tennant A. The Behcet's disease activity index. Rheumatology (Oxford). 2004 Jan;43(1):73-8. doi: 10.1093/rheumatology/keg453. Epub 2003 Jul 30. PMID: 12890862.	At week 8
Secondary	Disease activity assessed by Behcet's Disease Current Activity	Changes in Behcet's Disease Current Activity Form 2006 The score varies between 0 and 12, the higher the score the higher the disease activity.; Lawton G, Bhakta BB, Chamberlain MA, Tennant A. The Behcet's disease activity index. Rheumatology (Oxford). 2004 Jan;43(1):73-8. doi: 10.1093/rheumatology/keg453. Epub 2003 Jul 30. PMID: 12890862.	At week 16
Secondary	Disease activity assessed by Behcet's Disease Current Activity	Changes in Behcet's Disease Current Activity Form 2006 The score varies between 0 and 12, the higher the score the higher the disease activity.; Lawton G, Bhakta BB, Chamberlain MA, Tennant A. The Behcet's disease activity index. Rheumatology (Oxford). 2004 Jan;43(1):73-8. doi: 10.1093/rheumatology/keg453. Epub 2003 Jul 30. PMID: 12890862.	At week 24
Secondary	Disease activity assessed by Behcet's Syndrome Activity Score	Changes in Behcet's Syndrome Activity Score. It is a 10 items score. The score varies between 0 and 100. The higher the score the higher the disease activity.; Forbees C, Swearingen C, Yazici Y. Behcet's syndrome activity score (BSAS): a new disease activity assessment tool, composed of patient-derived measures only, is strongly correlated with the Behcet's Disease Current Activity Form (BDCAF) Arthritis Rheum. 2008;58(Suppl 9):S854-S855.	At week 8
Secondary	Disease activity assessed by Behcet's Syndrome Activity Score	Changes in Behcet's Syndrome Activity Score. It is a 10 items score. The score varies between 0 and 100. The higher the score the higher the disease activity.; Forbees C, Swearingen C, Yazici Y. Behcet's syndrome activity score (BSAS): a new disease activity assessment tool, composed of patient-derived measures only, is strongly correlated with the Behcet's Disease Current Activity Form (BDCAF) Arthritis Rheum. 2008;58(Suppl 9):S854-S855.	At week 16
Secondary	Disease activity assessed by Behcet's Syndrome Activity Score	Changes in Behcet's Syndrome Activity Score It is a 10 items score. The score varies between 0 and 100. The higher the score the higher the disease activity.; Forbees C, Swearingen C, Yazici Y. Behcet's syndrome activity score (BSAS): a new disease activity assessment tool, composed of patient-derived measures only, is strongly correlated with the Behcet's Disease Current Activity Form (BDCAF) Arthritis Rheum. 2008;58(Suppl 9):S854-S855.	week 24
Secondary	Changes in the number of other organs involved by Behcet Disease (BD)		At week 4
Secondary	Changes in the number of other organs involved by Behcet Disease (BD)		At week 8
Secondary	Changes in the number of other organs involved by Behcet Disease (BD)		At week 12
Secondary	Changes in the number of other organs involved by Behcet Disease (BD)		At week 16
Secondary	Changes in the number of other organs involved by Behcet Disease (BD)		At week 24
Secondary	Changes in the number of other organs involved by Behcet Disease (BD)		At week 36
Secondary	Changes in the number of other organs involved by Behcet Disease (BD)		At week 48
Secondary	Quality of Life assessed by Behcet's Disease Quality of Life Measure	It is a score composed of 30 items and the result varies between 0 and 30. The higher the score, the lower the quality of life.; G. Gilworth, MA Chamberlain, B. Bhakta, A. Silman, D. Haskard and A. Tennant. (2004), The Development of the BD-Qol: A Quality of Life Instrument Specific to Behçet's Disease., J Rheum, 31, 931-7	At week 16
Secondary	Quality of Life assessed by Behcet's Disease Quality of Life Measure	It is a score composed of 30 items and the result varies between 0 and 30. The higher the score, the lower the quality of life.; G. Gilworth, MA Chamberlain, B. Bhakta, A. Silman, D. Haskard and A. Tennant. (2004), The Development of the BD-Qol: A Quality of Life Instrument Specific to Behçet's Disease., J Rheum, 31, 931-7	At week 24
Secondary	Changes in Short Form (36) Health Survey for quality of life	The Short Form (36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability.; Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992;30:473-83.	At week 16
Secondary	Changes in Short Form (36) Health Survey for quality of life	The Short Form (36) Health Survey is a 36-item measure if health status. The score obtained varies between 0 and 100. The higher the score the less disability.; Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992;30:473-83.	At week 24
Secondary	Proportion of patients with adverse clinical events		at week 4
Secondary	Proportion of patients with adverse clinical events		at week 8
Secondary	Proportion of patients with adverse clinical events		at week 12
Secondary	Proportion of patients with adverse clinical events		at week 16
Secondary	Proportion of patients with adverse clinical events		at week 24
Secondary	Proportion of patients with adverse clinical events		at week 36
Secondary	Proportion of patients with adverse clinical events		at week 48
Secondary	Severity of adverse clinical events	It is determined according to the Common Terminology Criteria for Adverse Events (CTCAE). The grade varies from 1 to 5. Grade 1 corresponds to mild severity and grade 5 to death.	At week 4
Secondary	Severity of adverse clinical events	It is determined according to the Common Terminology Criteria for Adverse Events (CTCAE). The grade varies from 1 to 5. Grade 1 corresponds to mild severity and grade 5 to death. death.	At week 8
Secondary	Severity of adverse clinical events	It is determined according to the Common Terminology Criteria for Adverse Events (CTCAE). The grade varies from 1 to 5. Grade 1 corresponds to mild severity and grade 5 to death.	At week 12
Secondary	Severity of adverse clinical events	It is determined according to the Common Terminology Criteria for Adverse Events (CTCAE). The grade varies from 1 to 5. Grade 1 corresponds to mild severity and grade 5 to death.	At week 16
Secondary	Severity of adverse clinical events	It is determined according to the Common Terminology Criteria for Adverse Events (CTCAE). The grade varies from 1 to 5. Grade 1 corresponds to mild severity and grade 5 to death.	At week 24
Secondary	Severity of adverse clinical events	It is determined according to the Common Terminology Criteria for Adverse Events (CTCAE). The grade varies from 1 to 5. Grade 1 corresponds to mild severity and grade 5 to death.	At week 36
Secondary	Severity of adverse clinical events	It is determined according to the Common Terminology Criteria for Adverse Events (CTCAE). The grade varies from 1 to 5. Grade 1 corresponds to mild severity and grade 5 to death.	At week 48
Secondary	Changes in Tyndall score	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies from grade 0 to grade 4+. The higher the grade the higher the number of cells in the anterior chamber.	At week 8
Secondary	Changes in Tyndall score	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies from grade 0 to grade 4+. The higher the grade the higher the number of cells in the anterio chamber.	At week 16
Secondary	Changes in Tyndall score	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies from grade 0 to grade 4+. The higher the grade the higher the number of cells in the anterior chamber.	At week 24
Secondary	Changes in Tyndall score	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies from grade 0 to grade 4+. The higher the grade the higher the number of cells in the anterior chamber.	At week 36
Secondary	Changes in Tyndall score	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies from grade 0 to grade 4+. The higher the grade the higher the number of cells in the anterior chamber.	At week 48
Secondary	Changes in flare score	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies from grade 0 to 4+. The higher the score, the higher the inflammation.	At week 8
Secondary	Changes in flare score	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies from grade 0 to 4+. The higher the score, the higher the inflammation.	At week 16
Secondary	Changes in flare score	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies from grade 0 to 4+. The higher the score, the higher the inflammation.	At week 24
Secondary	Changes in flare score	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies from grade 0 to 4+. The higher the score, the higher the inflammation.	At week 36
Secondary	Changes in flare score	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies from grade 0 to 4+. The higher the score, the higher the inflammation.	At week 48
Secondary	Changes of Vitreous Haze	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies between 0 and 4. The higher the score the higher the inflammation.	At week 8
Secondary	Changes of Vitreous Haze	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies between 0 and 4. The higher the score the higher the inflammation.	At week 16
Secondary	Changes of Vitreous Haze	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies between 0 and 4. The higher the score the higher the inflammation.	At week 24
Secondary	Changes of Vitreous Haze	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies between 0 and 4. The higher the score the higher the inflammation.	At week 36
Secondary	Changes of Vitreous Haze	The score is calculated according to the Standardization of Uveitis Nomenclature (SUN). It varies between 0 and 4. The higher the score the higher the inflammation.	At week 48
Secondary	Changes in Best corrected visual acuity	Evaluated by Early Treatment Diabetic Retinopathy Study (ETDRS) letters score. The total score varies between 0 and 100. The higher score the better the visual acuity.; ETDRS Early Treatment Diabetic Retinopathy Study Research Group Treatment Diabetic Retinopathy Study design and baseline patient characteristics. ETDRS report number 7., Ophthalmology. 1991 May; 98(5 Suppl):741-756	At week 8
Secondary	Changes in Best corrected visual acuity	Evaluated by ETDRS letters score. The total score varies between 0 and 100. The higher score the better the visual acuity; ETDRS Early Treatment Diabetic Retinopathy Study Research Group Treatment Diabetic Retinopathy Study design and baseline patient characteristics. ETDRS report number 7., Ophthalmology. 1991 May; 98(5 Suppl):741-756	At week 16
Secondary	Changes in Best corrected visual acuity	Evaluated by ETDRS letters score. The total score varies between 0 and 100. The higher score the better the visual acuity; ETDRS Early Treatment Diabetic Retinopathy Study Research Group Treatment Diabetic Retinopathy Study design and baseline patient characteristics. ETDRS report number 7., Ophthalmology. 1991 May; 98(5 Suppl):741-756	At week 24
Secondary	Changes in Best corrected visual acuity	Evaluated by ETDRS letters score. The total score varies between 0 and 100. The higher score the better the visual acuity; ETDRS Early Treatment Diabetic Retinopathy Study Research Group Treatment Diabetic Retinopathy Study design and baseline patient characteristics. ETDRS report number 7., Ophthalmology. 1991 May; 98(5 Suppl):741-756	At week 36
Secondary	Changes in Best corrected visual acuity	Evaluated by ETDRS letters score. The total score varies between 0 and 100. The higher score the better the visual acuity; ETDRS Early Treatment Diabetic Retinopathy Study Research Group Treatment Diabetic Retinopathy Study design and baseline patient characteristics. ETDRS report number 7., Ophthalmology. 1991 May; 98(5 Suppl):741-756	At week 48
Secondary	Changes in central retinal thickness	Changes in central retinal thickness measured with Optical Coherence Tomography (OCT)	At week 8
Secondary	Changes in central retinal thickness	Changes in central retinal thickness measured with Optical Coherence Tomography (OCT)	At week 16
Secondary	Changes in central retinal thickness	Changes in central retinal thickness measured with Optical Coherence Tomography (OCT)	At week 24
Secondary	Changes in central retinal thickness	Changes in central retinal thickness measured with Optical Coherence Tomography (OCT)	At week 36
Secondary	Changes in central retinal thickness	Changes in central retinal thickness measured with Optical Coherence Tomography (OCT)	At week 48
Secondary	Percentage of patients with central retinal thickness <300 microns		At week 8
Secondary	Percentage of patients with central retinal thickness <300 microns		At week 16
Secondary	Percentage of patients with central retinal thickness <300 microns		At week 24
Secondary	Percentage of patients with central retinal thickness <300 microns		At week 36
Secondary	Percentage of patients with central retinal thickness <300 microns		At week 48
Secondary	Percentage of patients without retinal vessel leakage on retinal angiography	in case of retinal vasculitis	At week 16
Secondary	Percentage of patients without retinal vessel leakage on retinal angiography	in case of retinal vasculitis	At week 24
Secondary	Percentage of patients without retinal vessel leakage on retinal angiography	in case of retinal vasculitis	At week 36
Secondary	Percentage of patients without retinal vessel leakage on retinal angiography	in case of retinal vasculitis	At week 48