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UveitisPhase 3VISUAL lNCT01138657

Efficacy and Safety of Adalimumab in Patients With Active Uveitis

A Phase 3 study testing Adalimumab and Prednisone in people with Uveitis, run by AbbVie (prior sponsor, Abbott).

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Uveitis
What is being tested?
Adalimumab and Prednisone
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
239 participants
Where
No sites listed yet
Study dates
Aug 2010to Aug 2014
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.

Who cannot join

  • 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.
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  • 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.

About this study

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

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

Conditions
Uveitis
Being tested
Adalimumab, Prednisone, Placebo
Keywords
inflammation of uvea
Medical subject headings
Uveitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AdalimumabBiological

    Also called ABT-D2E7, Humira

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

  • PrednisoneDrug

    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.

  • PlaceboDrug

    Administered by subcutaneous injection

Study groups in NCT01138657
Study groupRoleWhat they receive
AdalimumabExperimentalParticipants 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.
Receives: Biological: Adalimumab; Drug: Prednisone
PlaceboPlacebo comparatorParticipants 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.
Receives: Drug: Prednisone; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (9)

  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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

    Measured: 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2010 (estimated)
  2. Study startAug 2010
  3. Primary completionJul 2014
  4. Study completionAug 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
239 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01138657
Sponsor's protocol ID
M10-877
Other IDs
2009-016095-68, 2009
Acronym
VISUAL l
Status last verified
Jul 2021
First submitted
14 May 2010
Last updated
7 Jul 2021
Data monitoring committee
Yes

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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Adalimumab and Prednisone in people with Uveitis, run by AbbVie (prior sponsor, Abbott).

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Aug 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to Treatment Failure on or After Week 6 (time frame: From Baseline until end of study (up to 80 weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01138657, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2021.

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