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NCT Number: NCT05874505

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

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

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Key information

Conditions

Behcet's Uveitis

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age >= 18 at Inclusion
  • 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).
  • 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
  • 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)
  • 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
  • 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.
  • Affiliation to a social security system. Patients affiliated to universal medical coverage (CMU) are eligible for the study

Exclusion criteria

  • Infectious uveitis, masquerade syndromes, or uveitis due to causes other than BD uveitis
  • Active tuberculosis or history of untreated tuberculosis and/or severe infection
  • Positive HIV antibody and/or positive hepatitis B surface antigen and/or positive hepatitis C RNA, results obtained within 1 month prior to inclusion
  • 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.
  • 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
  • Laboratory values assessed during Inclusion:
  • Neutrophil < 1.0 x 10^3 /mm3
  • Platelet count < 80 x 10^3 /mm3
  • ASAT or ALAT > 5 ULN
  • Treatment with anti-TNF and/or Tocilizumab therapy within 1 month prior to inclusion
  • 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
  • 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)
  • Any live (attenuated) vaccine within 4 weeks prior to inclusion
  • Breastfeeding or pregnant women

Treatment and study plan

Adalimumab

Drug

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

Tocilizumab

Drug

Tocilizumab 162 mg subcutaneous each week for 15 weeks

Primary outcomes

  1. Proportion of patients with complete remission of ocular involvement (Efficacy)

    Time frame: At week 16 after randomization

    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.

Secondary outcomes

  1. Percent of patients meeting the corticosteroid sparing targets

    Time frame: At week 16 after randomization

    lower than 0.1 mg/day/kg of prednisone

  2. Mean dose of corticosteroids

    Time frame: At week 16 after randomization

  3. Cumulative dose of corticosteroids

    Time frame: At week 16 after randomization

  4. Time to response onset

    Time frame: Up to week 48

  5. Erythrocyte sedimentation rate

    Time frame: At week 4

  6. Erythrocyte sedimentation rate

    Time frame: At week 8

  7. Erythrocyte sedimentation rate

    Time frame: At week 12

  8. Erythrocyte sedimentation rate

    Time frame: At week 16

  9. Erythrocyte sedimentation rate

    Time frame: At week 24

  10. Erythrocyte sedimentation rate

    Time frame: At week 36

  11. Erythrocyte sedimentation rate

    Time frame: At week 48

  12. C-reactive protein rate

    Time frame: At week 4

  13. C-reactive protein rate

    Time frame: At week 8

  14. C-reactive protein rate

    Time frame: At week 12

  15. C-reactive protein rate

    Time frame: At week 16

  16. C-reactive protein rate

    Time frame: At week 24

  17. C-reactive protein rate

    Time frame: At week 36

  18. C-reactive protein rate

    Time frame: At week 48

  19. Rate of relapses

    Time frame: up to 48 weeks

    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

  20. Time to occurrence of relapse or worsening of uveitis

    Time frame: up to 48 weeks

    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

  21. Disease activity assessed by Behcet's Disease Current Activity

    Time frame: At week 8

    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.

  22. Disease activity assessed by Behcet's Disease Current Activity

    Time frame: At week 16

    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.

  23. Disease activity assessed by Behcet's Disease Current Activity

    Time frame: At week 24

    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.

  24. Disease activity assessed by Behcet's Syndrome Activity Score

    Time frame: At week 8

    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.

  25. Disease activity assessed by Behcet's Syndrome Activity Score

    Time frame: At week 16

    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.

  26. Disease activity assessed by Behcet's Syndrome Activity Score

    Time frame: week 24

    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.

  27. Changes in the number of other organs involved by Behcet Disease (BD)

    Time frame: At week 4

  28. Changes in the number of other organs involved by Behcet Disease (BD)

    Time frame: At week 8

  29. Changes in the number of other organs involved by Behcet Disease (BD)

    Time frame: At week 12

  30. Changes in the number of other organs involved by Behcet Disease (BD)

    Time frame: At week 16

  31. Changes in the number of other organs involved by Behcet Disease (BD)

    Time frame: At week 24

  32. Changes in the number of other organs involved by Behcet Disease (BD)

    Time frame: At week 36

  33. Changes in the number of other organs involved by Behcet Disease (BD)

    Time frame: At week 48

  34. Quality of Life assessed by Behcet's Disease Quality of Life Measure

    Time frame: At week 16

    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

  35. Quality of Life assessed by Behcet's Disease Quality of Life Measure

    Time frame: At week 24

    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

  36. Changes in Short Form (36) Health Survey for quality of life

    Time frame: At week 16

    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.

  37. Changes in Short Form (36) Health Survey for quality of life

    Time frame: At week 24

    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.

  38. Proportion of patients with adverse clinical events

    Time frame: at week 4

  39. Proportion of patients with adverse clinical events

    Time frame: at week 8

  40. Proportion of patients with adverse clinical events

    Time frame: at week 12

  41. Proportion of patients with adverse clinical events

    Time frame: at week 16

  42. Proportion of patients with adverse clinical events

    Time frame: at week 24

  43. Proportion of patients with adverse clinical events

    Time frame: at week 36

  44. Proportion of patients with adverse clinical events

    Time frame: at week 48

  45. Severity of adverse clinical events

    Time frame: At week 4

    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.

  46. Severity of adverse clinical events

    Time frame: At week 8

    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.

  47. Severity of adverse clinical events

    Time frame: At week 12

    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.

  48. Severity of adverse clinical events

    Time frame: At week 16

    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.

  49. Severity of adverse clinical events

    Time frame: At week 24

    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.

  50. Severity of adverse clinical events

    Time frame: At week 36

    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.

  51. Severity of adverse clinical events

    Time frame: At week 48

    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.

  52. Changes in Tyndall score

    Time frame: At week 8

    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.

  53. Changes in Tyndall score

    Time frame: At week 16

    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.

  54. Changes in Tyndall score

    Time frame: At week 24

    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.

  55. Changes in Tyndall score

    Time frame: At week 36

    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.

  56. Changes in Tyndall score

    Time frame: At week 48

    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.

  57. Changes in flare score

    Time frame: At week 8

    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.

  58. Changes in flare score

    Time frame: At week 16

    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.

  59. Changes in flare score

    Time frame: At week 24

    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.

  60. Changes in flare score

    Time frame: At week 36

    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.

  61. Changes in flare score

    Time frame: At week 48

    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.

  62. Changes of Vitreous Haze

    Time frame: At week 8

    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.

  63. Changes of Vitreous Haze

    Time frame: At week 16

    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.

  64. Changes of Vitreous Haze

    Time frame: At week 24

    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.

  65. Changes of Vitreous Haze

    Time frame: At week 36

    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.

  66. Changes of Vitreous Haze

    Time frame: At week 48

    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.

  67. Changes in Best corrected visual acuity

    Time frame: At week 8

    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

  68. Changes in Best corrected visual acuity

    Time frame: At week 16

    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

  69. Changes in Best corrected visual acuity

    Time frame: At week 24

    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

  70. Changes in Best corrected visual acuity

    Time frame: At week 36

    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

  71. Changes in Best corrected visual acuity

    Time frame: At week 48

    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

  72. Changes in central retinal thickness

    Time frame: At week 8

    Changes in central retinal thickness measured with Optical Coherence Tomography (OCT)

  73. Changes in central retinal thickness

    Time frame: At week 16

    Changes in central retinal thickness measured with Optical Coherence Tomography (OCT)

  74. Changes in central retinal thickness

    Time frame: At week 24

    Changes in central retinal thickness measured with Optical Coherence Tomography (OCT)

  75. Changes in central retinal thickness

    Time frame: At week 36

    Changes in central retinal thickness measured with Optical Coherence Tomography (OCT)

  76. Changes in central retinal thickness

    Time frame: At week 48

    Changes in central retinal thickness measured with Optical Coherence Tomography (OCT)

  77. Percentage of patients with central retinal thickness <300 microns

    Time frame: At week 8

  78. Percentage of patients with central retinal thickness <300 microns

    Time frame: At week 16

  79. Percentage of patients with central retinal thickness <300 microns

    Time frame: At week 24

  80. Percentage of patients with central retinal thickness <300 microns

    Time frame: At week 36

  81. Percentage of patients with central retinal thickness <300 microns

    Time frame: At week 48

  82. Percentage of patients without retinal vessel leakage on retinal angiography

    Time frame: At week 16

    in case of retinal vasculitis

  83. Percentage of patients without retinal vessel leakage on retinal angiography

    Time frame: At week 24

    in case of retinal vasculitis

  84. Percentage of patients without retinal vessel leakage on retinal angiography

    Time frame: At week 36

    in case of retinal vasculitis

  85. Percentage of patients without retinal vessel leakage on retinal angiography

    Time frame: At week 48

    in case of retinal vasculitis

Study contacts

Contact information is provided by the study sponsor or research team.

Bahram BODAGHI, Pr

CONTACT

[email protected]

+33 1 42 16 37 28

Matthieu RESCHE-RIGON, Pr

CONTACT

[email protected]

+33 1 42 49 97 42

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Registry information

Official study 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

Acronym: UVB

Important dates

Study start
2023
Primary completion
2026
Study completion
2027
First posted
May 25, 2023
Registry last updated
May 25, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.