A study comparing the safety and efficacy of Adalimumab vs. Placebo in subjects with active
uveitis.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Inclusion Criteria:
- Subject is at least 18 years of age.
- Subject is diagnosed with non-infectious intermediate-, posterior-, or pan-uveitis.
- 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 TB. Only one TB test is required
to allow the subject in the study. Subjects with either negative PPD (< 5 mm of
induration) or negative QuantiFERON®-TB Gold test (or 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-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.
Site Reference ID/Investigator# 71298, Buenos Aires C1015ABO, Argentina
Site Reference ID/Investigator# 71316, Buenos Aires B1629ODT, Argentina
Site Reference ID/Investigator# 75253, Buenos Aires C1120AAN, Argentina
Site Reference ID/Investigator# 25724, East Melbourne 3002, Australia
Site Reference ID/Investigator# 25723, Nedlands 6009, Australia
Site Reference ID/Investigator# 25742, Vienna 1030, Austria
Site Reference ID/Investigator# 25746, Ghent 9000, Belgium
Site Reference ID/Investigator# 25747, Leuven 3000, Belgium
Site Reference ID/Investigator# 26016, Calgary T2H 0C8, Canada
Site Reference ID/Investigator# 26015, London N6A 4V2, Canada
Site Reference ID/Investigator# 26010, Montreal H1T 2M4, Canada
Site Reference ID/Investigator# 26011, Montreal H3A 1A1, Canada
Site Reference ID/Investigator# 47398, Ottawa K1H 8L6, Canada
Site Reference ID/Investigator# 77942, Vancouver V5Z 3N9, Canada
Site Reference ID/Investigator# 82673, Vancouver V6Z 1Y6, Canada
Site Reference ID/Investigator# 25749, Prague 2 128 00, Czech Republic
Site Reference ID/Investigator# 25751, Aarhus 8000, Denmark
Site Reference ID/Investigator# 25750, Glostrup 2600, Denmark
Site Reference ID/Investigator# 25759, Nantes Cedex 1 44093, France
Site Reference ID/Investigator# 25753, Paris Cedex 14 75679, France
Site Reference ID/Investigator# 97935, Paris 75012, France
Site Reference ID/Investigator# 25752, Strasbourg Cedex 67091, France
Site Reference ID/Investigator# 25762, Freiburg 79106, Germany
Site Reference ID/Investigator# 25761, Heidelberg 69120, Germany
Site Reference ID/Investigator# 76753, Kiel 24105, Germany
Site Reference ID/Investigator# 25760, Muenster 48145, Germany
Site Reference ID/Investigator# 72274, Munich 80336, Germany
Site Reference ID/Investigator# 25764, Tuebingen 72076, Germany
Site Reference ID/Investigator# 74639, Larissa 41100, Greece
Site Reference ID/Investigator# 25766, Petach Tikva 49100, Israel
Site Reference ID/Investigator# 25769, Tel Aviv 64239, Israel
Site Reference ID/Investigator# 78353, Bologna 40138, Italy
Site Reference ID/Investigator# 25772, Milan 20132, Italy
Site Reference ID/Investigator# 47962, Negrar (Verona) 37024, Italy
Site Reference ID/Investigator# 71853, Reggio Emilia 42100, Italy
Site Reference ID/Investigator# 26329, Fukuoka-shi, Japan
Site Reference ID/Investigator# 88033, Nagakute-shi, Japan
Site Reference ID/Investigator# 26322, Sapporo-shi, Japan
Site Reference ID/Investigator# 29274, Sendai-shi, Japan
Site Reference ID/Investigator# 26328, Suita-shi, Japan
Site Reference ID/Investigator# 26323, Tokyo, Japan
Site Reference ID/Investigator# 26324, Tokyo, Japan
Site Reference ID/Investigator# 26327, Yokohama-shi, Japan
Site Reference ID/Investigator# 71553, Mexico DF 04030, Mexico
Site Reference ID/Investigator# 73173, Nuevo Leon 64020, Mexico
Site Reference ID/Investigator# 71293, Tijuana 22320, Mexico
Site Reference ID/Investigator# 74813, Gdansk-Chelm 80-809, Poland
Site Reference ID/Investigator# 74816, Wroclaw 50-556, Poland
Site Reference ID/Investigator# 25776, Coimbra 3000-075, Portugal
Site Reference ID/Investigator# 25775, Porto 4200-319, Portugal
Site Reference ID/Investigator# 25777, Barcelona 08028, Spain
Site Reference ID/Investigator# 25780, Valencia 46014, Spain
Site Reference ID/Investigator# 25783, Valladolid 47011, Spain
Site Reference ID/Investigator# 75613, Bern 3012, Switzerland
Site Reference ID/Investigator# 75233, Lausanne 1004, Switzerland
Site Reference ID/Investigator# 25788, Aberdeen AB25 2ZD, United Kingdom
Site Reference ID/Investigator# 25787, Bristol BS1 2LX, United Kingdom
Site Reference ID/Investigator# 73354, Liverpool L7 8XP, United Kingdom
Site Reference ID/Investigator# 25789, London EC1V 2PD, United Kingdom
Site Reference ID/Investigator# 25610, Phoenix, Arizona 85014, United States
Site Reference ID/Investigator# 49742, Beverly Hills, California 90211, United States
Site Reference ID/Investigator# 27867, Miami, Florida 33143, United States
Site Reference ID/Investigator# 58286, Tamarac, Florida 33321, United States
Site Reference ID/Investigator# 26183, Tampa, Florida 33603, United States
Site Reference ID/Investigator# 25605, Atlanta, Georgia 30322, United States
Site Reference ID/Investigator# 25594, Chicago, Illinois 60612, United States
Site Reference ID/Investigator# 86493, Chicago, Illinois 60611, United States
Site Reference ID/Investigator# 37131, Ellsworth, Maine 04605, United States
Site Reference ID/Investigator# 25595, Baltimore, Maryland 21287, United States
Site Reference ID/Investigator# 75433, Baltimore, Maryland 21287, United States
Site Reference ID/Investigator# 25596, Detroit, Michigan 48201, United States
Site Reference ID/Investigator# 25586, Palisades Park, New Jersey 07650, United States
Site Reference ID/Investigator# 25589, New York, New York 10003, United States
Site Reference ID/Investigator# 25588, Belmont, North Carolina 28012, United States
Site Reference ID/Investigator# 26726, Durham, North Carolina 27705, United States
Site Reference ID/Investigator# 63243, Winston-Salem, North Carolina 27157, United States
Site Reference ID/Investigator# 25606, Oklahoma City, Oklahoma 73104, United States
Site Reference ID/Investigator# 25607, Portland, Oregon 97239, United States
Site Reference ID/Investigator# 25590, Philadelphia, Pennsylvania 19104, United States
Site Reference ID/Investigator# 27402, Dallas, Texas 75231, United States
Site Reference ID/Investigator# 25609, Houston, Texas 77025, United States
Site Reference ID/Investigator# 25612, Houston, Texas 77030, United States
Site Reference ID/Investigator# 81173, McAllen, Texas 78503, United States
Site Reference ID/Investigator# 25598, San Antonio, Texas 78240, United States
Site Reference ID/Investigator# 93193, Temple, Texas 76508, United States
Site Reference ID/Investigator# 25616, Salt Lake City, Utah 84132, United States
Site Reference ID/Investigator# 25599, Norfolk, Virginia 23502, United States
Site Reference ID/Investigator# 97495, Morgantown, West Virginia 26506, United States