Efficacy and Safety of Adalimumab in Patients With Active 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 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
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: 239.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: inflammation of uvea

Summary:

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

Eligibility criteria:

        Inclusion Criteria:

          -  Subject is at least 18 years of age.

          -  Subject is diagnosed with non-infectious intermediate-, posterior-, or panuveitis.

          -  Subject must have active disease at the Baseline visit as defined by the presence of
             at least 1 of the following parameters in at least one eye despite at least 2 weeks of
             maintenance therapy with oral prednisone ≥ 10 mg/day to ≤ 60 mg/day (or oral
             corticosteroid equivalent):

               -  Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion

               -  ≥ 2+ anterior chamber cells (Standardization of Uveitis Nomenclature [SUN]
                  criteria)

               -  ≥ 2+ vitreous haze (National Eye Institute [NEI]/SUN criteria)

          -  Subject is on oral prednisone ≥ 10 mg/day to ≤ 60 mg/day (or oral corticosteroid
             equivalent) for at least 2 weeks prior to Screening and remains on the same dose from
             Screening to Baseline visit.

          -  Subject with documented prior adequate response to oral corticosteroids (equivalent of
             oral prednisone up to 1 mg/kg/day).

          -  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 prior inadequate response to high-dose oral corticosteroids

          -  Subject with confirmed or suspected infectious uveitis, including but not limited to
             infectious uveitis due to TB, cytomegalovirus (CMV), Human T-Lymphotropic Virus Type 1
             (HTLV-1), Whipple's disease, Herpes Zoster virus (HZV), Lyme disease, toxoplasmosis
             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 (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 had 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.

          -  If entering the study on 1 concomitant immunosuppressive therapy, dose has been
             increased within the last 28 days prior to 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 received Retisert® (glucocorticosteroids implant) within 3 years prior to
             the Baseline visit or that has had complications related to the device. Subject has
             had Retisert® (glucocorticosteroids implant) removed within 90 days prior to the
             Baseline visit or has had complications related to the removal of the device.

          -  Subject has received intraocular or periocular corticosteroids within 30 days prior to
             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 severe vitreous haze that precludes visualization of the fundus at the
             Baseline visit.

          -  Subject has received Ozurdex® (dexamethasone implant) within 6 months 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 has received intravitreal methotrexate within 90 days prior to the Baseline
             visit

          -  Subject on systemic carbonic anhydrase inhibitor within 1 week prior to Screening
             visit.

          -  Subject with macular edema as the only sign of uveitis.

          -  Subject with a history of scleritis.

          -  Subject with intolerance to high-dose oral corticosteroids (equivalent of oral
             prednisone 1 mg/kg/day or 60 to 80 mg/day).

          -  Subject on cyclophosphamide within 30 days prior to the Baseline visit.