Clinical trial NCT01138657: Efficacy and Safety of Adalimumab in Patients With Active Uveitis
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 Intermediate Uveitis, Posterior Uveitis, or Panuveitis - Including a Sub-study in Japanese Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uveitis
Keywords: inflammation of uvea
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2010-06-07
Enrollment: 239
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Time to Treatment Failure on or After Week 6
timeFrame: From Baseline until end of study (up to 80 weeks)
Secondary outcomes:
measure: Change in Anterior Chamber (AC) Cell Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
timeFrame: From Baseline to Week 6 and at the Final/Early Termination Visit (up to 80 weeks)
measure: Change in Vitreous Haze (VH) Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
timeFrame: From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)
measure: 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
timeFrame: From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)
measure: Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 6
timeFrame: From Baseline until the Final Visit (up to 80 weeks)
measure: Percent Change in Central Retinal Thickness in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
timeFrame: Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)
measure: Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
timeFrame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
measure: Change in VFQ-25 Distance Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
timeFrame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
measure: Change in VFQ-25 Near Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
timeFrame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
measure: Change in VFQ-25 Ocular Pain Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
timeFrame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: Andy Payne, PhD
role: STUDY_DIRECTOR
References:
citation: Jaffe GJ, Dick AD, Brezin AP, Nguyen QD, Thorne JE, Kestelyn P, Barisani-Asenbauer T, Franco P, Heiligenhaus A, Scales D, Chu DS, Camez A, Kwatra NV, Song AP, Kron M, Tari S, Suhler EB. Adalimumab in Patients with Active Noninfectious Uveitis. N Engl J Med. 2016 Sep 8;375(10):932-43. doi: 10.1056/NEJMoa1509852.
citation: Sheppard J, Joshi A, Betts KA, Hudgens S, Tari S, Chen N, Skup M, Dick AD. Effect of Adalimumab on Visual Functioning in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, and Panuveitis in the VISUAL-1 and VISUAL-2 Trials. JAMA Ophthalmol. 2017 Jun 1;135(6):511-518. doi: 10.1001/jamaophthalmol.2017.0603.
citation: Grewal DS, O'Sullivan ML, Kron M, Jaffe GJ. Association of Disorganization of Retinal Inner Layers With Visual Acuity In Eyes With Uveitic Cystoid Macular Edema. Am J Ophthalmol. 2017 May;177:116-125. doi: 10.1016/j.ajo.2017.02.017. Epub 2017 Feb 22.