Efficacy and Safety of Adalimumab in Patients With Active Uveitis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 July 2021
• Main ID: NCT01138657
• Date of registration: 14/05/2010
• Prospective Registration: Yes
• Primary sponsor: AbbVie (prior sponsor, Abbott)
• Public title: Efficacy and Safety of Adalimumab in Patients With Active Uveitis VISUAL l
• Scientific 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
• Date of first enrolment: August 2010
• Target sample size: 239
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01138657
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, Greece, Israel, Italy, Japan, Mexico, Netherlands, Poland, Portugal, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Andy Payne, PhD
• Affiliation: AbbVie

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Uveitis

Intervention(s)

Biological: Adalimumab

Drug: Placebo

Drug: Prednisone

Primary Outcome(s)

Time to Treatment Failure on or After Week 6 [Time Frame: From Baseline until end of study (up to 80 weeks)]

Secondary Outcome(s)

Change in Anterior Chamber (AC) Cell Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [Time Frame: From Baseline to Week 6 and at the Final/Early Termination Visit (up to 80 weeks)]

Percent Change in Central Retinal Thickness in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [Time Frame: Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)]

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 [Time Frame: From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)]

Change in VFQ-25 Distance Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [Time Frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)]

Change in VFQ-25 Near Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [Time Frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)]

Change in VFQ-25 Ocular Pain Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [Time Frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)]

Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [Time Frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)]

Change in Vitreous Haze (VH) Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit [Time Frame: From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)]

Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 6 [Time Frame: From Baseline until the Final Visit (up to 80 weeks)]

Secondary ID(s)

M10-877

2009-016095-68

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 22/08/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01138657