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CompletedNCT01138657VISUAL lUpdated Jul 7, 2021Results posted

Efficacy and Safety of Adalimumab in Patients With Active Uveitis

A Phase 3 interventional study of Adalimumab and Prednisone in Uveitis, sponsored by AbbVie (prior sponsor, Abbott). Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-07-07.

Sponsored by AbbVie (prior sponsor, Abbott) · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
239
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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

02

Conditions studied

  • Uveitis

Browse trials for

Keywords

  • inflammation of uvea
03

In context

Uveitis

335 studies on the registry are indexed under Uveitis; 37 are open to participants now.

This study's enrollment of 239 is above the median of 30 across 208 interventional studies indexed under Uveitis.

Browse Uveitis studies →

Lead sponsor

AbbVie (prior sponsor, Abbott) is the lead sponsor of 215 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
239 participants (actual)

Study arms

  • Experimental
    Adalimumab

    Participants received adalimumab 80 mg subcutaneous loading dose at Baseline followed by 40 mg doses every other week (eow) starting at Week 1 for a maximum of 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.

    Biological: Adalimumab · Drug: Prednisone

  • Placebo comparator
    Placebo

    Participants received placebo subcutaneous injection at Baseline followed by eow dosing starting at Week 1 for up to 80 weeks or until treatment failure. Participants continued to receive prednisone orally, 60 mg/day at study entry followed by a protocol-defined mandatory taper until Week 15.

    Drug: Prednisone · Drug: Placebo

Interventions

  • BiologicalAdalimumab

    Administered subcutaneously as an 80 mg loading dose (2 syringes) at Baseline followed by a 40 mg dose eow starting at Week 1.

    Also known as: ABT-D2E7, Humira

  • DrugPrednisone

    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.

  • DrugPlacebo

    Administered by subcutaneous injection

06

What researchers measure

Primary outcomes

  1. Time to Treatment Failure on or After Week 6

    Time to treatment failure was analyzed using Kaplan-Meier methods. Treatment failures on or after Week 6 were counted as events. Dropouts for reasons other than treatment failure at any time during the study were censored at the dropout date. To be considered a treatment failure, ≥ 1 of these criteria had to be present in at least 1 eye: * New active, inflammatory chorioretinal or retinal vascular lesions relative to Baseline * Inability to achieve ≤ 0.5+ at Week 6 or a 2-step increase relative to best state achieved at all visits after Week 6 in anterior chamber cell grade or vitreous haze grade * Worsening of best corrected visual acuity by ≥ 15 letters relative to best state achieved. Per protocol, the primary analysis was performed in the Main Study population which included all randomized participants recruited outside Japan; for completeness results are also reported below for the Integrated dataset which includes participants recruited in Japan.

    Time frame: From Baseline until end of study (up to 80 weeks)

Secondary outcomes

  1. Change in Anterior Chamber (AC) Cell Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

    Slit lamp examinations were conducted at each visit to assess AC cell count. The number of AC cells observed within a 1 mm × 1 mm slit beam was used to determine the grade according to the Standardization of Uveitis Nomenclature (SUN) criteria: Grade 0 = \< 1 cell; Grade 0.5+ = 1-5 cells; Grade 1+ = 6-15 cells; Grade 2+ = 16-25 cells; Grade 3+ = 26-50 cells; Grade 4+ = \> 50 cells.

    Time frame: From Baseline to Week 6 and at the Final/Early Termination Visit (up to 80 weeks)

  2. Change in Vitreous Haze (VH) Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

    Vitreous haze was measured using dilated indirect ophthalmoscopy (DIO) and assessed by the Investigator according to National Eye Institute (NEI) and SUN criteria: Grade 0: No evident vitreous haze; Grade 0.5+: Slight blurring of the optic disc margin because of the haze; normal striations and reflex of the nerve fiber layer cannot be visualized; Grade 1+: Permits a better definition of both the optic nerve head and the retinal vessels (compared to higher grades); Grade 2+: Permits better visualization of the retinal vessels (compared to higher grades); Grade 3+: Permits the observer to see the optic nerve head, but the borders are quite blurry; Grade 4+: Optic nerve head is obscured.

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

  3. 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

    Using corrective lenses based on that visit's refraction testing, participant's best corrected visual acuity was measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart.

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

  4. Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 6

    Optical coherence tomography was performed at every visit using 1 of 3 approved machines. Images were evaluated by a central reader. Macular edema was defined as cystoid macular edema. OCT evidence of macular edema on or after Week 6 was to be counted as an event. Dropouts due to reasons other than OCT evidence of macular edema were to be considered as censored observations at the time of dropping out.

    Time frame: From Baseline until the Final Visit (up to 80 weeks)

  5. Percent Change in Central Retinal Thickness in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

    Central retinal thickness was measured using optical coherence tomography and assessed by a central reader.

    Time frame: Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)

  6. Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

    The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The overall composite score ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.

    Time frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)

  7. Change in VFQ-25 Distance Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

    The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The distance vision subscore is calculated from the answers to 3 distance vision-related questions and ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.

    Time frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)

  8. Change in VFQ-25 Near Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

    The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The distance vision subscore is calculated from the answers to 3 near vision-related questions and ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.

    Time frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)

  9. Change in VFQ-25 Ocular Pain Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

    The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The ocular pain subscore is calculated from the answers to 2 ocular pain-related questions and ranges from 0 to 100, where higher scores or increases in score indicate less pain.

    Time frame: Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)

07

Results

Posted Aug 22, 2016

Participant flow

This study includes a Japan sub-study. 239 participants with active non-infectious intermediate uveitis, posterior uveitis, or panuveitis were randomized worldwide, including 223 participants at 67 sites in Australia, Europe, Israel, Latin America, and North America (Main Study), and 16 participants randomized at 7 sites in Japan (Japan sub-study).

Participant flow — Overall Study
MilestonePlaceboAdalimumab
Started120119
Enrolled in main study112111
Enrolled in japan sub-study88
Completed112101
Not completed818
Withdrew: Adverse event310
Withdrew: Lack of efficacy21
Withdrew: Lost to follow-up03
Withdrew: Miscellaneous reasons34

Outcome measures

PrimaryTime to Treatment Failure on or After Week 6

Time to treatment failure was analyzed using Kaplan-Meier methods. Treatment failures on or after Week 6 were counted as events. Dropouts for reasons other than treatment failure at any time during the study were censored at the dropout date. To be considered a treatment failure, ≥ 1 of these criteria had to be present in at least 1 eye: * New active, inflammatory chorioretinal or retinal vascular lesions relative to Baseline * Inability to achieve ≤ 0.5+ at Week 6 or a 2-step increase relative to best state achieved at all visits after Week 6 in anterior chamber cell grade or vitreous haze grade * Worsening of best corrected visual acuity by ≥ 15 letters relative to best state achieved. Per protocol, the primary analysis was performed in the Main Study population which included all randomized participants recruited outside Japan; for completeness results are also reported below for the Integrated dataset which includes participants recruited in Japan.

Time frame:
From Baseline until end of study (up to 80 weeks)
Reported as:
Median · months
Time to Treatment Failure on or After Week 6
monthsMain Study: PlaceboMain Study: AdalimumabIntegrated Study (Main + Japan Sub-study): PlaceboIntegrated Study (Main + Japan Sub-study): Adalimumab
Time to Treatment Failure on or After Week 63.0 (1.5 to 5.6)5.6 (3.0 to NA)3.0 (1.5 to 5.6)4.8 (2.8 to NA)
Statistical analysis
  • Main Study: Placebo vs Main Study: Adalimumab · Log Rank · p = <0.001 · Hazard ratio (hr): 0.50 · 95% CI 0.36 to 0.70
  • Integrated Study (Main + Japan Sub-study): Placebo vs Integrated Study (Main + Japan Sub-study): Adalimumab · Log Rank · p = < 0.001 · Hazard ratio (hr): 0.56 · 95% CI 0.40 to 0.76
SecondaryChange in Anterior Chamber (AC) Cell Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

Slit lamp examinations were conducted at each visit to assess AC cell count. The number of AC cells observed within a 1 mm × 1 mm slit beam was used to determine the grade according to the Standardization of Uveitis Nomenclature (SUN) criteria: Grade 0 = \< 1 cell; Grade 0.5+ = 1-5 cells; Grade 1+ = 6-15 cells; Grade 2+ = 16-25 cells; Grade 3+ = 26-50 cells; Grade 4+ = \> 50 cells.

Time frame:
From Baseline to Week 6 and at the Final/Early Termination Visit (up to 80 weeks)
Reported as:
Mean · units on a scale
Change in Anterior Chamber (AC) Cell Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
units on a scaleMain Study: PlaceboMain Study: AdalimumabIntegrated Study (Main + Japan Sub-study): PlaceboIntegrated Study (Main + Japan Sub-study): Adalimumab
Left Eye0.59 ± 0.9350.35 ± 0.7630.56 ± 0.9130.35 ± 0.744
Right Eye0.69 ± 1.0670.36 ± 0.7460.65 ± 1.0390.36 ± 0.727
Statistical analysis
  • Main Study: Placebo vs Main Study: Adalimumab · ANOVA · p = 0.011 · Mean difference: -0.29 · 95% CI -0.51 to -0.07The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.
  • Integrated Study (Main + Japan Sub-study): Placebo vs Integrated Study (Main + Japan Sub-study): Adalimumab · ANOVA · p = 0.019 · Mean difference: -0.25 · 95% CI -0.46 to -0.04The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.
SecondaryChange in Vitreous Haze (VH) Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

Vitreous haze was measured using dilated indirect ophthalmoscopy (DIO) and assessed by the Investigator according to National Eye Institute (NEI) and SUN criteria: Grade 0: No evident vitreous haze; Grade 0.5+: Slight blurring of the optic disc margin because of the haze; normal striations and reflex of the nerve fiber layer cannot be visualized; Grade 1+: Permits a better definition of both the optic nerve head and the retinal vessels (compared to higher grades); Grade 2+: Permits better visualization of the retinal vessels (compared to higher grades); Grade 3+: Permits the observer to see the optic nerve head, but the borders are quite blurry; Grade 4+: Optic nerve head is obscured.

Time frame:
From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)
Reported as:
Mean · units on a scale
Change in Vitreous Haze (VH) Grade in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
units on a scaleMain Study: PlaceboMain Study: AdalimumabIntegrated Study (Main + Japan Sub-study): PlaceboIntegrated Study (Main + Japan Sub-study): Adalimumab
Left Eye0.33 ± 0.6660.11 ± 0.5590.34 ± 0.6750.11 ± 0.547
Right Eye0.45 ± 0.7810.13 ± 0.6480.49 ± 0.8150.16 ± 0.648
Statistical analysis
  • Main Study: Placebo vs Main Study: Adalimumab · ANOVA · p = <0.001 · Mean difference: -0.27 · 95% CI -0.43 to -0.11The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.
  • Integrated Study (Main + Japan Sub-study): Placebo vs Integrated Study (Main + Japan Sub-study): Adalimumab · ANOVA · p = <0.001 · Mean difference: -0.28 · 95% CI -0.43 to -0.12The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.
SecondaryChange 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

Using corrective lenses based on that visit's refraction testing, participant's best corrected visual acuity was measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR chart.

Time frame:
From Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)
Reported as:
Mean · logMAR
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
logMARMain Study: PlaceboMain Study: AdalimumabIntegrated Study (Main + Japan Sub-study): PlaceboIntegrated Study (Main + Japan Sub-study): Adalimumab
Left Eye0.12 ± 0.1690.07 ± 0.1600.11 ± 0.1790.07 ± 0.164
Right Eye0.13 ± 0.3200.04 ± 0.1430.13 ± 0.3280.05 ± 0.145
Statistical analysis
  • Main Study: Placebo vs Main Study: Adalimumab · ANOVA · p = 0.003 · Mean difference: -0.07 · 95% CI -0.11 to -0.02The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.
  • Integrated Study (Main + Japan Sub-study): Placebo vs Integrated Study (Main + Japan Sub-study): Adalimumab · ANOVA · p = 0.008 · Mean difference: -0.06 · 95% CI -0.10 to -0.02The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.
SecondaryTime to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 6

Optical coherence tomography was performed at every visit using 1 of 3 approved machines. Images were evaluated by a central reader. Macular edema was defined as cystoid macular edema. OCT evidence of macular edema on or after Week 6 was to be counted as an event. Dropouts due to reasons other than OCT evidence of macular edema were to be considered as censored observations at the time of dropping out.

Time frame:
From Baseline until the Final Visit (up to 80 weeks)
Reported as:
Median · months
Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 6
monthsMain Study: PlaceboMain Study: AdalimumabIntegrated Study (Main + Japan Sub-study): PlaceboIntegrated Study (Main + Japan Sub-study): Adalimumab
Time to Optical Coherence Tomography (OCT) Evidence of Macular Edema in At Least 1 Eye On or After Week 66.2 (1.4 to NA)11.1 (2.6 to 15.9)3.7 (1.4 to NA)9.2 (2.7 to 15.9)
Statistical analysis
  • Main Study: Placebo vs Main Study: Adalimumab · Log Rank · p = 0.231 · Hazard ratio (hr): 0.70 · 95% CI 0.39 to 1.26The hazard ratio of adalimumab versus placebo was calculated using proportional hazards regression with treatment as factor.
  • Integrated Study (Main + Japan Sub-study): Placebo vs Integrated Study (Main + Japan Sub-study): Adalimumab · Log Rank · p = 0.191 · Hazard ratio (hr): 0.68 · 95% CI 0.38 to 1.21The hazard ratio of adalimumab versus placebo was calculated using proportional hazards regression with treatment and race (Japanese versus non-Japanese) as factors.
SecondaryPercent Change in Central Retinal Thickness in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

Central retinal thickness was measured using optical coherence tomography and assessed by a central reader.

Time frame:
Baseline to Week 6 and Final/Early Termination Visit (up to 80 weeks)
Reported as:
Mean · percent change
Percent Change in Central Retinal Thickness in Each Eye From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
percent changeMain Study: PlaceboMain Study: AdalimumabIntegrated Study (Main + Japan Sub-study): PlaceboIntegrated Study (Main + Japan Sub-study): Adalimumab
Left eye (n=100, 100, 107, 108)20.2 ± 52.019.6 ± 29.7619.0 ± 50.5713.9 ± 53.95
Right eye (n=102, 101, 108, 109)22.0 ± 62.488.2 ± 25.7821.7 ± 60.7514.5 ± 57.05
Statistical analysis
  • Main Study: Placebo vs Main Study: Adalimumab · ANOVA · p = 0.020 · Mean difference: -11.4 · 95% CI -20.9 to -1.8The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.
  • Integrated Study (Main + Japan Sub-study): Placebo vs Integrated Study (Main + Japan Sub-study): Adalimumab · Chi-squared, Corrected · p = 0.428 · Mean difference: -5.1 · 95% CI -17.7 to 7.5The mean difference between treatment groups with its 95% confidence interval is based on individual data from all eyes adjusted for correlated measurements within a subject in an analysis of variance (ANOVA) model.
SecondaryChange in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The overall composite score ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.

Time frame:
Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
Reported as:
Mean · units on a scale
Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
units on a scaleMain Study: PlaceboMain Study: AdalimumabIntegrated Study (Main + Japan Sub-study): PlaceboIntegrated Study (Main + Japan Sub-study): Adalimumab
Change in Visual Functioning Questionnaire 25 (VFQ-25) Composite Score From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit-5.50 ± 11.968-1.30 ± 10.980-5.34 ± 11.899-1.68 ± 10.924
Statistical analysis
  • Main Study: Placebo vs Main Study: Adalimumab · ANOVA · p = 0.010 · Mean difference: 4.20 · 95% CI 1.02 to 7.38ANOVA with treatment as a factor.
  • Integrated Study (Main + Japan Sub-study): Placebo vs Integrated Study (Main + Japan Sub-study): Adalimumab · ANOVA · p = 0.019 · Mean difference: 3.67 · 95% CI 0.62 to 6.71ANOVA with treatment and race (Japanese versus non-Japanese) as factors.
SecondaryChange in VFQ-25 Distance Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The distance vision subscore is calculated from the answers to 3 distance vision-related questions and ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.

Time frame:
Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
Reported as:
Mean · units on a scale
Change in VFQ-25 Distance Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
units on a scaleMain Study: PlaceboMain Study: AdalimumabIntegrated Study (Main + Japan Sub-study): PlaceboIntegrated Study (Main + Japan Sub-study): Adalimumab
Change in VFQ-25 Distance Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit-5.64 ± 14.654-3.77 ± 13.414-5.72 ± 14.531-4.42 ± 13.871
Statistical analysis
  • Main Study: Placebo vs Main Study: Adalimumab · ANOVA · p = 0.346 · Mean difference: 1.86 · 95% CI -2.03 to 5.75ANOVA with treatment as a factor.
  • Integrated Study (Main + Japan Sub-study): Placebo vs Integrated Study (Main + Japan Sub-study): Adalimumab · ANOVA · p = 0.496 · Mean difference: 1.31 · 95% CI -2.47 to 5.09ANOVA with treatment and race (Japanese versus non-Japanese) as factors.
SecondaryChange in VFQ-25 Near Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The distance vision subscore is calculated from the answers to 3 near vision-related questions and ranges from 0 to 100, where higher scores or increases in score indicate better vision-related functioning.

Time frame:
Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
Reported as:
Mean · units on a scale
Change in VFQ-25 Near Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
units on a scaleMain Study: PlaceboMain Study: AdalimumabIntegrated Study (Main + Japan Sub-study): PlaceboIntegrated Study (Main + Japan Sub-study): Adalimumab
Change in VFQ-25 Near Vision Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit-8.09 ± 17.754-2.97 ± 16.784-7.65 ± 17.808-3.52 ± 16.494
Statistical analysis
  • Main Study: Placebo vs Main Study: Adalimumab · ANOVA · p = 0.036 · Mean difference: 5.12 · 95% CI 0.34 to 9.90ANOVA with treatment as a factor.
  • Integrated Study (Main + Japan Sub-study): Placebo vs Integrated Study (Main + Japan Sub-study): Adalimumab · ANOVA · p = 0.077 · Mean difference: 4.14 · 95% CI -0.45 to 8.72ANOVA with treatment and race (Japanese versus non-Japanese) as factors.
SecondaryChange in VFQ-25 Ocular Pain Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit

The National Eye Institute VFQ-25 is an ocular disease-specific survey that measures the influence of visual disability and visual symptoms on generic health domains such as emotional well-being and social functioning, in addition to task-oriented domains related to daily visual functioning. The VFQ-25 consists of a base set of 25 vision-targeted questions plus an additional single-item general health rating question. The ocular pain subscore is calculated from the answers to 2 ocular pain-related questions and ranges from 0 to 100, where higher scores or increases in score indicate less pain.

Time frame:
Baseline to Week 6 and Final/Early Termination Visit (up 80 weeks)
Reported as:
Mean · units on a scale
Change in VFQ-25 Ocular Pain Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit
units on a scaleMain Study: PlaceboMain Study: AdalimumabIntegrated Study (Main + Japan Sub-study): PlaceboIntegrated Study (Main + Japan Sub-study): Adalimumab
Change in VFQ-25 Ocular Pain Subscore From Best State Achieved Prior to Week 6 to the Final/Early Termination Visit-12.62 ± 21.435-2.60 ± 15.342-12.39 ± 20.841-3.56 ± 16.056
Statistical analysis
  • Main Study: Placebo vs Main Study: Adalimumab · ANOVA · p = <0.001 · Mean difference: 10.02 · 95% CI 4.86 to 15.19ANOVA with treatment as a factor.
  • Integrated Study (Main + Japan Sub-study): Placebo vs Integrated Study (Main + Japan Sub-study): Adalimumab · ANOVA · p = <0.001 · Mean difference: 8.83 · 95% CI 3.88 to 13.79ANOVA with treatment and race (Japanese versus non-Japanese) as factors.

Adverse events

Collected over From the first study drug administration until 70 days following the last study drug administration or until rollover into the extension study. Median duration of treatment was 91 days in the placebo arm and 129 days in the adalimumab arm.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo—5/120 (4.2%)61/120 (50.8%)
Adalimumab—16/119 (13.4%)71/119 (59.7%)
Most frequent serious events
Showing 10 of 25
Most frequent serious events
EventPlaceboAdalimumab
ANGLE CLOSURE GLAUCOMAEye disorders0/1201/119
ANAPHYLACTIC REACTIONImmune system disorders0/1201/119
PILONIDAL CYSTInfections and infestations0/1201/119
PNEUMONIAInfections and infestations0/1201/119
TUBERCULOSISInfections and infestations0/1201/119
UPPER RESPIRATORY TRACT INFECTIONInfections and infestations0/1201/119
URINARY TRACT INFECTIONInfections and infestations0/1201/119
ACCIDENTAL OVERDOSEInjury, poisoning and procedural complications0/1201/119
LIGAMENT RUPTUREInjury, poisoning and procedural complications0/1201/119
TENDON RUPTUREInjury, poisoning and procedural complications0/1201/119
Most frequent other events
Showing 10 of 20
Most frequent other events
EventPlaceboAdalimumab
NASOPHARYNGITISInfections and infestations11/12021/119
HEADACHENervous system disorders16/12013/119
UVEITISEye disorders8/12012/119
FATIGUEGeneral disorders7/12012/119
ARTHRALGIAMusculoskeletal and connective tissue disorders12/12010/119
EYE PAINEye disorders2/1209/119
BACK PAINMusculoskeletal and connective tissue disorders3/1209/119
INSOMNIAPsychiatric disorders8/1209/119
VISION BLURREDEye disorders2/1208/119
BRONCHITISInfections and infestations4/1207/119

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboAdalimumabTotal
Mean43.19 ± 14.33143.46 ± 15.45843.33 ± 14.872
Age, Customized
Age, Customized(participants)PlaceboAdalimumabTotal
< 40 years5647103
40 - 64 years5456110
≥ 65 years101626
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboAdalimumabTotal
Female7366139
Male4753100
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)PlaceboAdalimumabTotal
White9189180
Black121123
Asian101222
American Indian/Alaskan Native101
Native Hawaiian or Other Pacific Islander000
Other5611
Multi Race112
Type of Uveitis
Type of Uveitis(participants)PlaceboAdalimumabTotal
Intermediate242549
Posterior383876
Panuveitis5856114
Diagnosis
Diagnosis(participants)PlaceboAdalimumabTotal
Idiopathic504090
Birdshot Choroidopathy212445
Multifocal Choroiditis And Panuveitis5813
Vogt Koyanagi Harada141226
Sarcoid121224
Behcet's41418
Other14923
Eye Affected
Eye Affected(participants)PlaceboAdalimumabTotal
Left5611
Right4711
Both111106217
Duration of Uveitis
Duration of Uveitis(months)PlaceboAdalimumabTotal
Mean58.56 ± 85.30841.18 ± 53.53049.90 ± 71.660
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Study locations

No study locations are listed for this record.

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References and documents

Publications

  • 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. PubMed 27602665 ↗
  • 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. PubMed 28426849 ↗
  • 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. PubMed 28237411 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 7, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT01138657
Lead sponsor
AbbVie (prior sponsor, Abbott)
Responsible party
Sponsor
First posted
Jun 7, 2010
Start date
Aug 2010
Primary completion
Jul 2014
Completion
Aug 2014
Results posted
Aug 22, 2016
Last update
Jul 7, 2021

Study contacts

Andy Payne, PhD
study director · AbbVie

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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