Efficacy and Safety of Adalimumab in Patients With Active Uveitis

NCT01138657 | Completed Phase 3 Results DMC

• 2 other identifiers: M10-8772009-016095-68
• Study Type: interventional
• Target: 239
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Uveitis

Keywords

inflammation of uvea

Outcome Measures

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.

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

Secondary Outcomes (9)

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

  From Baseline to Week 6 and at the Final/Early Termination Visit (up to 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

  From 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

  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

  From Baseline until the Final 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

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

Study Arms (2)

Adalimumab

EXPERIMENTAL

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

PLACEBO COMPARATOR

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

Adalimumab BIOLOGICAL

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

Adalimumab

Prednisone DRUG

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.

Adalimumab; Placebo

Placebo DRUG

Administered by subcutaneous injection

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Related Publications (3)

• 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.

  PMID: 27602665 RESULT

• 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.

  PMID: 28426849 DERIVED

• 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.

  PMID: 28237411 DERIVED

Related Links

• This clinical study may be evaluating a usage that is not currently FDA-approved. Please see US Prescribing Information for approved uses.

MeSH Terms

Conditions

Uveitis

Interventions

Adalimumab; Prednisone

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor, Abbott)

800-633-9110

Study Officials

• Andy Payne, PhD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2010
• First Posted: June 7, 2010
• Study Start: August 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: August 1, 2014
• Last Updated: July 7, 2021
• Results First Posted: August 22, 2016

Record last verified: 2021-07