Efficacy and Safety of Adalimumab Plus Medium Dose Oral Glucocorticosteroid for Refractory Behçet's Uveitis
Primary Purpose
Uveitis
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Adalimumab plus different doses of oral glucocorticosteroid
Sponsored by
About this trial
This is an interventional treatment trial for Uveitis
Eligibility Criteria
Inclusion Criteria:
- Behçet's disease (BD) patients fulfilling the International Criteria for Behçet's disease (ICBD) published in 2013 with recent recurrence of pan- or posterior uveitis
- The patient should be on ≥10mg/d oral prednisone or equivalent
Exclusion Criteria:
- Previous treatment with TNFα inhibitors within 3 months
- Pregnancy, breast feeding women
- Malignancy
- Heart failure
- Demyelinating diseases
- Renal impairment (creatinine > 1.5 mg/dl)
- Depression or other psychic disorders
- History of acute or chronic inflammatory joint or autoimmune disease
- Patients with severe extra-ocular involvement other than oral/genital ulcer and skin involvement
- Organ or bone marrow transplant recipient, cardiac failure > NYHA III
- Acute liver disease with ALT or SGPT 2x above normal
- White blood cell count < 3500/mm^3
- Platelet count < 100000/mm^3
- Hgb < 8.5g/dl
- T-SPOT TB: ≥200 SFCs per 10^6 PBMC
- Active peptic ulcer, systemic or local infection, moderate to severe osteoporosis or other contraindications of intermediate dose corticosteroids
- Other severe ocular diseases or intraocular surgery within 3 months
- Media opacity precluding a clear view of the fundus
- Positive screen test for HBV, HCV, HIV infection or syphilis
- Body weight <45 kg
- Alcohol abuse or drug abuse
- Mental impairment
- Uncooperative attitude
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Medium dose group (Adalimumab plus medium dose oral glucocorticosteroid)
High dose group (Adalimumab plus high dose oral glucocorticosteroid)
Arm Description
Patients will be given adalimumab with 30mg daily prednisone or equivalent with a fixed slow tapering plan.
Patients will be given adalimumab with 60mg daily prednisone or equivalent with a fixed slow tapering plan.
Outcomes
Primary Outcome Measures
Uveitis control
Inflammation control according to SUN criteria (two steps decrease of anterior chamber cell or vitreous haze or decreased to zero) or active retinal lesion recession with vitreous haze less than 0.5 grade
Secondary Outcome Measures
Best corrected visual acuity (BCVA)
BCVA was transformed into logMar form
Extent of vascular leakage
Vascular leakage was quantified based on the method developed by the Angiography Scoring for Uveitis Working Group (ASUWOG), in which vascular leakage in the posterior pole and in each peripheral quadrant was scored 1 if limited
BOS 24 score
BOS 24 scoring system refers to article "Behc et's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab
Uveitis deterioration
Inflammation deterioration according to SUN criteria (two steps increase of anterior chamber cell or vitreous haze or increases to grade 4) or new active retinal lesions or new onset of retinal vasculitis
Full Information
NCT ID
NCT05105347
First Posted
October 19, 2021
Last Updated
November 1, 2021
Sponsor
Peking Union Medical College Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05105347
Brief Title
Efficacy and Safety of Adalimumab Plus Medium Dose Oral Glucocorticosteroid for Refractory Behçet's Uveitis
Official Title
Efficacy and Safety of Adalimumab Plus Medium Dose Oral Glucocorticosteroid for Refractory Behçet's Uveitis, Compared With Adalimumab Plus High Dose Oral Glucocorticosteroid, a Non-inferior, Multi-center, Randomized Controlled Trial.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 10, 2021 (Anticipated)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Peking Union Medical College Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is a multi-center randomized non-inferiority study that aims to observe the short-term (3 months) efficacy and safety of adalimumab plus medium-dose glucocorticosteroid (30mg/d prednisone or equivalent) with slow tapering for recurrent Behçet's uveitis (BU) attack compared with adalimumab plus high-dose glucocorticosteroid (60mg/d prednisone or equivalent) with slow tapering.
Detailed Description
According to the most recent European League Against Rheumatism (EULAR) recommendation, patients presenting with an initial or recurrent episode of acute sight-threatening uveitis should be treated with high-dose glucocorticoids, infliximab or interferon-α. Adalimumab, another TNFα antagonist, is also considered as an alternative for infliximab and have proved its efficacy in several RCTs in the treatment of non-infectious intermediate, posterior and pan-uveitis. As higher dose glucocorticosteroid have greater side effects, this study aims to evaluate the non-inferior efficacy and safety of adalimumab plus medium-dose glucocorticosteroid compared with adalimumab plus high-dose glucocorticosteroid (and slow tapering) for recurrent posterior or pan-uveitis attack of Behcet's uveitis. Refractory BU is defined as relapse of posterior or panuveitis with at least 10mg daily prednisone (or equivalent). The acute attack will be controlled with adalimumab (80mg once, 40mg q2w thereafter) plus medium dose initial oral glucocorticosteroid (30mg daily prednisone or equivalent) in the "medium dose" group or plus high dose oral glucocorticosteroid (60mg daily prednisone or equivalent) in the "high dose" group with fixed tapering protocols. Patients will be followed up at 2w, 4w, 8w, and 12w after initiation of treatment. The primary endpoint is the inflammatory control rate. Secondary endpoints are BCVA, vascular leakage score on fundus fluorescein angiography (FFA), BOS 24 score and uveitis deterioration rate. The safety profiles of both groups will be also monitored.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uveitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
130 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Medium dose group (Adalimumab plus medium dose oral glucocorticosteroid)
Arm Type
Experimental
Arm Description
Patients will be given adalimumab with 30mg daily prednisone or equivalent with a fixed slow tapering plan.
Arm Title
High dose group (Adalimumab plus high dose oral glucocorticosteroid)
Arm Type
Active Comparator
Arm Description
Patients will be given adalimumab with 60mg daily prednisone or equivalent with a fixed slow tapering plan.
Intervention Type
Drug
Intervention Name(s)
Adalimumab plus different doses of oral glucocorticosteroid
Other Intervention Name(s)
Humira, prednisone
Intervention Description
A loading dose of 80mg adalimumab will be given subcutaneously and then change to 40mg adalimumab every two weeks. Medium dose oral glucocorticosteroid (30mg/d prednisone or equivalent) will be given to the experimental dose group and high dose oral glucocorticosteroid (60mg/d prednisone or equivalent) will be given to the high dose group.
Primary Outcome Measure Information:
Title
Uveitis control
Description
Inflammation control according to SUN criteria (two steps decrease of anterior chamber cell or vitreous haze or decreased to zero) or active retinal lesion recession with vitreous haze less than 0.5 grade
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Best corrected visual acuity (BCVA)
Description
BCVA was transformed into logMar form
Time Frame
3 months
Title
Extent of vascular leakage
Description
Vascular leakage was quantified based on the method developed by the Angiography Scoring for Uveitis Working Group (ASUWOG), in which vascular leakage in the posterior pole and in each peripheral quadrant was scored 1 if limited
Time Frame
3 months
Title
BOS 24 score
Description
BOS 24 scoring system refers to article "Behc et's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab
Time Frame
3 months
Title
Uveitis deterioration
Description
Inflammation deterioration according to SUN criteria (two steps increase of anterior chamber cell or vitreous haze or increases to grade 4) or new active retinal lesions or new onset of retinal vasculitis
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Behçet's disease (BD) patients fulfilling the International Criteria for Behçet's disease (ICBD) published in 2013 with recent recurrence of pan- or posterior uveitis
The patient should be on ≥10mg/d oral prednisone or equivalent
Exclusion Criteria:
Previous treatment with TNFα inhibitors within 3 months
Pregnancy, breast feeding women
Malignancy
Heart failure
Demyelinating diseases
Renal impairment (creatinine > 1.5 mg/dl)
Depression or other psychic disorders
History of acute or chronic inflammatory joint or autoimmune disease
Patients with severe extra-ocular involvement other than oral/genital ulcer and skin involvement
Organ or bone marrow transplant recipient, cardiac failure > NYHA III
Acute liver disease with ALT or SGPT 2x above normal
White blood cell count < 3500/mm^3
Platelet count < 100000/mm^3
Hgb < 8.5g/dl
T-SPOT TB: ≥200 SFCs per 10^6 PBMC
Active peptic ulcer, systemic or local infection, moderate to severe osteoporosis or other contraindications of intermediate dose corticosteroids
Other severe ocular diseases or intraocular surgery within 3 months
Media opacity precluding a clear view of the fundus
Positive screen test for HBV, HCV, HIV infection or syphilis
Body weight <45 kg
Alcohol abuse or drug abuse
Mental impairment
Uncooperative attitude
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hang Song, MD
Phone
+8615600612346
Email
songhang_pumch@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Chan Zhao, MD
Phone
+8613810454083
Email
zhaochan@pumch.cn
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
email contact person if needed
Citations:
PubMed Identifier
27602665
Citation
Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med. 2016 Sep 8;375(10):932-43. doi: 10.1056/NEJMoa1509852.
Results Reference
background
PubMed Identifier
24359625
Citation
Levy-Clarke G, Jabs DA, Read RW, Rosenbaum JT, Vitale A, Van Gelder RN. Expert panel recommendations for the use of anti-tumor necrosis factor biologic agents in patients with ocular inflammatory disorders. Ophthalmology. 2014 Mar;121(3):785-96.e3. doi: 10.1016/j.ophtha.2013.09.048. Epub 2013 Dec 17.
Results Reference
background
PubMed Identifier
26162757
Citation
Vallet H, Riviere S, Sanna A, Deroux A, Moulis G, Addimanda O, Salvarani C, Lambert M, Bielefeld P, Seve P, Sibilia J, Pasquali J, Fraison J, Marie I, Perard L, Bouillet L, Cohen F, Sene D, Schoindre Y, Lidove O, Le Hoang P, Hachulla E, Fain O, Mariette X, Papo T, Wechsler B, Bodaghi B, Rigon MR, Cacoub P, Saadoun D; French Behcet Network. Efficacy of anti-TNF alpha in severe and/or refractory Behcet's disease: Multicenter study of 124 patients. J Autoimmun. 2015 Aug;62:67-74. doi: 10.1016/j.jaut.2015.06.005. Epub 2015 Jul 8.
Results Reference
background
PubMed Identifier
24482146
Citation
Kaburaki T, Namba K, Sonoda KH, Kezuka T, Keino H, Fukuhara T, Kamoi K, Nakai K, Mizuki N, Ohguro N; Ocular Behcet Disease Research Group of Japan. Behcet's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab. Jpn J Ophthalmol. 2014 Mar;58(2):120-30. doi: 10.1007/s10384-013-0294-0. Epub 2014 Jan 31.
Results Reference
background
Learn more about this trial
Efficacy and Safety of Adalimumab Plus Medium Dose Oral Glucocorticosteroid for Refractory Behçet's Uveitis
We'll reach out to this number within 24 hrs