Efficacy and Safety of Adalimumab in Subjects With Inactive Uveitis
Condition: Uveitis
MeSH terms: Uveitis
Intervention: Adalimumab; Prednisone; Placebo
Intervention description: Administered subcutaneously as an 80 mg loading dose (2 syringes) at Baseline followed by 40 mg eow starting at Week 1.; Administered orally, 10 - 35 mg/day at study entry followed by a protocol-defined mandatory taper schedule in which all subjects continuing in the study were to discontinue prednisone no later than Week 19.; Administered by subcutaneous injection
Intervention MeSH terms: Prednisone; Adalimumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 261.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Uveitis

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject is diagnosed with non-infectious intermediate, posterior, or panuveitis.

          -  Subject that for ≥ 28 days prior to the Baseline visit has inactive disease and is
             taking ≥ 10 mg of oral prednisone to maintain this inactive state and fulfillment of
             all 3 of the following criteria based on the Investigator's clinical judgment at the
             Screening and Baseline visits for both eyes:

               -  Subject without active, inflammatory chorioretinal and/or inflammatory retinal
                  vascular lesions.

               -  Subject with anterior chamber cell grade ≤ 0.5+ according to Standardization of
                  Uveitis Nomenclature (SUN) criteria.

               -  Subject with vitreous haze grade ≤ 0.5+ according to National Eye Institute
                  (NEI)/SUN criteria.

          -  Subject is on oral prednisone 10 to 35 mg/day (or oral corticosteroid equivalent) at
             Baseline and the dose has not been increased in the past 28 days or decreased in the
             past 14 days.

          -  Subject must have a documented history of experiencing at least one disease flare
             within 18 months of the Screening visit. This flare has to occur during or up to a
             maximum of 28 days after tapering off the oral corticosteroid therapy.

          -  Subjects who do not have previous, active or latent tuberculosis (TB). Only one TB
             test is required to allow the subject in the study. Subjects with either negative
             purified protein derivative (PPD) (< 5 mm of induration) or negative QuantiFERON®-TB
             Gold test (or interferon-gamma release assay (IGRA) equivalent) are eligible. Subjects
             with a repeat indeterminate QuantiFERON®-TB Gold test (or IGRA equivalent) result are
             not eligible. Note, that only one TB screening test is allowed and required. A repeat
             QuantiFERON®-TB Gold test (or IGRA equivalent) is not permitted if the PPD skin test
             is positive. The TB screening tests are diagnostic tests. In the event of a negative
             TB screening test, the results are to be interpreted in the context of the patient's
             epidemiology, history, exam findings, etc. and it is the responsibility of the
             investigator to determine if a patient has previous, active or latent tuberculosis or
             not. Under no circumstances can a patient with a positive PPD result or positive
             QuantiFERON®-TB Gold test (or IGRA equivalent) enter the study.

        Exclusion Criteria:

          -  Subject with isolated anterior uveitis.

          -  Subject with confirmed or suspected infectious uveitis, including but not limited to
             infectious uveitis due to TB, cytomegalovirus (CMV), Lyme disease, toxoplasmosis,
             human T-lymphotropic virus type 1 (HTLV-1) infection, Whipple's disease, herpes zoster
             virus (HZV) and herpes simplex virus (HSV).

          -  Subject with serpiginous choroidopathy.

          -  Subject with corneal or lens opacity that precludes visualization of the fundus or
             that likely requires cataract surgery during the duration of the trial.

          -  Subject with intraocular pressure of ≥ 25 mmHg and on ≥ 2 glaucoma medications or
             evidence of glaucomatous optic nerve injury.

          -  Subject with best corrected visual acuity (BCVA) less than 20 letters (ETDRS [Early
             Treatment Diabetic Retinopathy Study]) in at least one eye at the Baseline visit.

          -  Subject with intermediate uveitis or panuveitis that has signs of intermediate uveitis
             (e.g. presence or history of snowbanking or snowballs) and symptoms and/or magnetic
             resonance imaging (MRI) findings suggestive of a demyelinating disease such as
             multiple sclerosis. All subjects with intermediate uveitis or panuveitis that have
             signs of intermediate uveitis (e.g. presence or history of snowbanking or snowballs)
             must have a brain MRI within 90 days prior to the Baseline visit.

          -  Subject has previous exposure to anti-tumor necrosis factor (TNF) therapy or any
             biologic therapy (except intravitreal anti- vascular endothelial growth factor (VEGF)
             therapy) with a potential therapeutic impact on non-infectious uveitis.

          -  Subject on concomitant immunosuppressive therapy other than methotrexate,
             cyclosporine, mycophenolate mofetil or an equivalent drug to mycophenolate mofetil
             (e.g., mycophenolic acid), azathioprine or tacrolimus within 28 days of Baseline or
             has discontinued an immunosuppressive therapy including methotrexate, cyclosporine,
             mycophenolate mofetil or an equivalent drug to mycophenolate mofetil (e.g.,
             mycophenolic acid), azathioprine or tacrolimus within 28 days of Baseline.

          -  If entering the study on one concomitant immunosuppressive therapy, dose has not been
             stable for at least 28 days prior to the Baseline visit or is not within the following
             allowable doses at the Baseline visit:

               -  Methotrexate (MTX) ≤ 25 mg per week

               -  Cyclosporine ≤ 4 mg/kg per day

               -  Mycophenolate mofetil ≤ 2 grams per day or an equivalent drug to mycophenolate
                  mofetil (e.g. mycophenolic acid) at an equivalent dose approved by the Medical
                  Monitor

               -  Azathioprine ≤ 175 mg per day

               -  Tacrolimus (oral formulation) ≤ 8 mg per day

          -  Subject has Retisert® (glucocorticosteroids implant) within 3 years prior to the
             Baseline visit or has had complications related to the device. Subject has had
             Retisert® (glucocorticosteroid implant) removed within 90 days prior to the Baseline
             visit or has had complications related to removal of the device.

          -  Subject has received intraocular or periocular corticosteroids within 90 days prior to
             the Baseline visit.

          -  Subject with proliferative or severe non-proliferative diabetic retinopathy or
             clinically significant macular edema due to diabetic retinopathy.

          -  Subject with neovascular/wet age-related macular degeneration.

          -  Subject with abnormality of vitreo-retinal interface (i.e., vitreomacular traction,
             epiretinal membranes, etc.) with the potential for macular structural damage
             independent of the inflammatory process.

          -  Subject with cystoid macular edema unless the retinal changes are persistent, residual
             and stable as defined by the SUN criteria (persistent is > 3 months duration).

          -  Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to the
             Baseline visit.

          -  Subject has received intravitreal methotrexate within 90 days prior to the Baseline
             visit.

          -  Subject has received intravitreal anti-VEGF therapy:

               -  within 45 days of the Baseline visit for Lucentis® (ranibizumab) or Avastin®
                  (bevacizumab);

               -  or within 60 days of the Baseline visit for anti-VEGF Trap (Aflibercept).

          -  Subject on systemic carbonic anhydrase inhibitor within 1 week prior to Screening
             visit.

          -  Subject with a history of scleritis.

          -  Subject on cyclophosphamide within 30 days prior to the Baseline visit.