Clinical Trial: Efficacy and Safety of Adalimumab in Patients With Active Uveitis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab as Maintenance Therapy in Subjects Requiring High Dose Corticosteroids for Active Non-infectious

Brief Summary: A study comparing the safety and efficacy of adalimumab compared with placebo in patients with active uveitis.

Detailed Summary:
Sponsor: AbbVie (prior sponsor, Abbott)

Current Primary Outcome: Time to Treatment Failure on or After Week 6 [ Time Frame: From Baseline until end of study (up to 80 weeks) ]

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.



Original Primary Outcome: Time to Treatment Failure [ Time Frame: As described above. ]

-Occurrence of one of following: New active, inflammatory chorioretinal and/or inflammatory retinal vascular lesions; Inability to achieve ≤ 0.5+ AC cell grade; Inability to achieve ≤ 0.5+ vitreous haze grade; Worsening of BCVA by ≥ 3 lines or 15 letters.

Time Frame: Evaluated at the Week 6 visit

-Occurrence of one of following: New active, inflammatory chorioretinal and/or inflammatory retinal vascular lesions; 2-step increase in AC cells; 2-step increase in vitreous haze; Worsening of BCVA by ≥ 3 lines or 15 letters.

Time Frame: Evaluated at all visits after Week 6 (up to 80 weeks)



Current Secondary Outcome:

  • Change in Anterior Chamber (AC) Cell Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [ Time Frame: From Baseline to Week 6 and at the Final/Early Termination Visit (up to 80 weeks) ]

    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.

  • Change in Vitreous Haze (VH) Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [ Time Frame: From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks) ]

    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.

  • 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 [ Time Frame: From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks) ]
    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 to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 6 [ Time Frame: From Baseline until the Final Visit (up to 80 weeks) ]

    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.

  • Percent Change in Central Retinal Thickness in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [ Time Frame: Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks) ]
    Central retinal thickness was measured using optical coherence tomography and assessed by a central reader.
  • Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [ Time Frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks) ]

    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.

  • Change in VFQ-25 Distance Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [ Time Frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks) ]

    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

    Original Secondary Outcome:

    • Change in Vitreous Haze grade (NEI/SUN criteria) [ Time Frame: Baseline to final visit (Final Visit could occur at any point up to 80 weeks) ]
    • Change in logMar BCVA [ Time Frame: Baseline to final visit (Final Visit could occur at any point up to 80 weeks) ]
    • Time to OCT evidence of macular edema [ Time Frame: Evaluated at all visits after Week 6 (Final Visit could occur at any point up to 80 weeks) ]
    • Change in central retinal thickness [ Time Frame: Baseline to final visit (Final Visit could occur at any point up to 80 weeks) ]
    • Change in NEI Visual Functioning Questionnaire (VFQ-25) [ Time Frame: Baseline to final visit (Final Visit could occur at any point up to 80 weeks) ]


    Information By: AbbVie

    Dates:
    Date Received: May 14, 2010
    Date Started: August 2010
    Date Completion:
    Last Updated: July 11, 2016
    Last Verified: July 2016