A study comparing the safety and efficacy of adalimumab compared with placebo in patients with active uveitis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
239
Administered subcutaneously as an 80 mg loading dose (2 syringes) at Baseline followed by a 40 mg dose eow starting at Week 1.
Administered orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper schedule in which all participants continuing in the study were to discontinue prednisone no later than Week 15.
Administered by subcutaneous injection
Time to Treatment Failure on or After Week 6
Time to treatment failure was analyzed using Kaplan-Meier methods. Treatment failures on or after Week 6 were counted as events. Dropouts for reasons other than treatment failure at any time during the study were censored at the dropout date. To be considered a treatment failure, ≥ 1 of these criteria had to be present in at least 1 eye: * New active, inflammatory chorioretinal or retinal vascular lesions relative to Baseline * Inability to achieve ≤ 0.5+ at Week 6 or a 2-step increase relative to best state achieved at all visits after Week 6 in anterior chamber cell grade or vitreous haze grade * Worsening of best corrected visual acuity by ≥ 15 letters relative to best state achieved. Per protocol, the primary analysis was performed in the Main Study population which included all randomized participants recruited outside Japan; for completeness results are also reported below for the Integrated dataset which includes participants recruited in Japan.
Time frame: From Baseline until end of study (up to 80 weeks)
Change in Anterior Chamber (AC) Cell Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
Slit lamp examinations were conducted at each visit to assess AC cell count. The number of AC cells observed within a 1 mm × 1 mm slit beam was used to determine the grade according to the Standardization of Uveitis Nomenclature (SUN) criteria: Grade 0 = \< 1 cell; Grade 0.5+ = 1-5 cells; Grade 1+ = 6-15 cells; Grade 2+ = 16-25 cells; Grade 3+ = 26-50 cells; Grade 4+ = \> 50 cells.
Time frame: From Baseline to Week 6 and at the Final/Early Termination Visit (up to 80 weeks)
Change in Vitreous Haze (VH) Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
Vitreous haze was measured using dilated indirect ophthalmoscopy (DIO) and assessed by the Investigator according to National Eye Institute (NEI) and SUN criteria: Grade 0: No evident vitreous haze; Grade 0.5+: Slight blurring of the optic disc margin because of the haze; normal striations and reflex of the nerve fiber layer cannot be visualized; Grade 1+: Permits a better definition of both the optic nerve head and the retinal vessels (compared to higher grades); Grade 2+: Permits better visualization of the retinal vessels (compared to higher grades); Grade 3+: Permits the observer to see the optic nerve head, but the borders are quite blurry; Grade 4+: Optic nerve head is obscured.
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Time frame: From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)
Change In Logarithm of the Minimum Angle of Resolution (LogMAR) Best Corrected Visual Acuity (BCVA) In Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
Using corrective lenses based on that visit's refraction testing, participant's best corrected visual acuity was measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart.
Time frame: From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)
Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 6
Optical coherence tomography was performed at every visit using 1 of 3 approved machines. Images were evaluated by a central reader. Macular edema was defined as cystoid macular edema. OCT evidence of macular edema on or after Week 6 was to be counted as an event. Dropouts due to reasons other than OCT evidence of macular edema were to be considered as censored observations at the time of dropping out.
Time frame: From Baseline until the Final Visit (up to 80 weeks)
Percent Change in Central Retinal Thickness in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
Central retinal thickness was measured using optical coherence tomography and assessed by a central reader.
Time frame: Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)
Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The overall composite score ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.
Time frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
Change in VFQ-25 Distance Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The distance vision subscore is calculated from the answers to 3 distance vision-related questions and ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.
Time frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
Change in VFQ-25 Near Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The distance vision subscore is calculated from the answers to 3 near vision-related questions and ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.
Time frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
Change in VFQ-25 Ocular Pain Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The ocular pain subscore is calculated from the answers to 2 ocular pain-related questions and ranges from 0 to 100, where higher scores or increases in score indicate less pain.
Time frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)