Clinical Trial: Efficacy and Safety of Adalimumab in Subjects With Inactive 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 in Subjects With Inactive Non-infectious Intermediate Uveitis, Posterior Uveit

Brief Summary: A study comparing the safety and efficacy of adalimumab compared with. placebo in adults with inactive non-infectious intermediate uveitis, posterior uveitis, or panuveitis.

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

Current Primary Outcome: Time to Treatment Failure on or After Week 2 [ Time Frame: From Baseline until end of study (up to 80 weeks) ]

Treatment failure was defined by the occurrence of a uveitis flare (the inability to maintain disease control). To be considered treatment failure, ≥ 1 of these criteria had to be present in at least 1 eye at Week 2 or all other visits:

  • New active, inflammatory chorioretinal, and/or inflammatory retinal vascular lesions relative to Baseline
  • 2-step increase relative to Baseline in anterior chamber cell grade or vitreous haze grade
  • Worsening of best corrected visual acuity by ≥ 15 letters relative to baseline.

Time to treatment failure was analyzed using the Kaplan-Meier method. Dropouts for reasons other than treatment failure at any time during the study were censored at the drop out date.

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: Evaluated at all visits after Baseline ]

Treatment Failure is defined by the occurrence of one of the 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.


Current Secondary Outcome:

  • Change in Anterior Chamber (AC) Cell Grade in Each Eye From Baseline to the Final/Early Termination Visit [ Time Frame: Baseline 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 Baseline to the Final/Early Termination Visit [ Time Frame: Baseline 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 Baseline to the Final/Early Termination Visit [ Time Frame: Baseline 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. On the logMAR scale, 0 is equivalent to 20/20 visual acuity, the range of normal vision is considered to be from -0.2 - 0.1; higher values indicate visual impairment.
  • Time to Optimal Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 2 [ 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 2 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 Baseline to the Final/Early Termination Visit. [ Time Frame: Baseline and Final/Early Termination Visit (up to 80 weeks) ]
    Central retinal thickness was measured using OCT and assessed by a central reader.
  • Change in Visual Functioning Questionnaire 25 (VFQ-25) Total Score From Baseline to the Final/Early Termination Visit [ Time Frame: Baseline 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 Subscore Distance Vision From Baseline to the Final/Early Termination Visit [ Time Frame: Baseline 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 q

    Original Secondary Outcome:

    • Proportion of subjects that taper down to 5 mg/day of prednisone [ Time Frame: Between Weeks 4 and 10 ]
    • Proportion of subjects that discontinue prednisone [ Time Frame: Between Weeks 12 and 20 ]
    • Change in Vitreous Haze grade (NEI/SUN criteria) [ Time Frame: Evaluate from Baseline to Final Visit ]
    • Change in logMAR BCVA [ Time Frame: Evaluate from Baseline to Final Visit ]
    • OCT evidence of macular edema [ Time Frame: Evaluate at all visits after Baseline ]
    • Change in central retinal thickness [ Time Frame: Evaluate from Baseline to Final Visit ]
    • Change in NEI Visual Functioning Questionnaire (VFQ-25) [ Time Frame: Evaluate from Baseline to Final Visit ]


    Information By: AbbVie

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