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Efficacy and Safety of Adalimumab in Subjects With Inactive Uveitis (Visual II)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by AbbVie
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier:
NCT01124838
First received: May 14, 2010
Last updated: October 10, 2014
Last verified: October 2014
  Purpose

A study comparing the safety and efficacy of Adalimumab vs. Placebo in subjects with inactive uveitis.


Condition Intervention Phase
Uveitis
Drug: adalimumab
Drug: prednisone
Drug: adalimumab placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter Study of the Efficacy and Safety of the Human Anti-TNF Monoclonal Antibody Adalimumab in Subjects With Inactive Non-infectious Intermediate, Posterior, or Pan-Uveitis

Resource links provided by NLM:


Further study details as provided by AbbVie:

Primary Outcome Measures:
  • Time to Treatment Failure [ Time Frame: Evaluated at all visits after Baseline ] [ Designated as safety issue: No ]
    Treatment Failure is defined by the occurrence of one of the following relative to baseline: new active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesions; 2 step increase in (Anterior Chamber) AC cells; 2 step increase in vitreous haze; worsening of Best Corrected Visual Acuity (BCVA) by >/=15 letters.


Secondary Outcome Measures:
  • Change in Anterior Chamber (AC) cell grade in each eye. [ Time Frame: Evaluate from Baseline to the Final/Early Termination visit. ] [ Designated as safety issue: No ]
    Final Visit could occur at any point up to 80 weeks.

  • Change in Vitreous Haze grade (NEI/SUN criteria) in each eye. [ Time Frame: Evaluate from Baseline to the Final/Early Termination visit. ] [ Designated as safety issue: No ]
    Final Visit could occur at any point up to 80 weeks.

  • Change in logarithm of the minimum angle of resolution (logMAR) BCVA in each eye. [ Time Frame: Evaluate from Baseline to the Final/Early Termination visit. ] [ Designated as safety issue: No ]
    Final Visit could occur at any point up to 80 weeks.

  • Time to optical coherence tomography (OCT) evidence of macular edema in at least one eye. [ Time Frame: Evaluate at all visits after Baseline. ] [ Designated as safety issue: No ]
  • Percent change in central retinal thickness in each eye. [ Time Frame: Evaluate from Baseline to the Final/Early Termination visit. ] [ Designated as safety issue: No ]
    Final Visit could occur at any point up to 80 weeks.

  • Change in NEI Visual Functioning Questionnaire (VFQ-25) composite score. [ Time Frame: Evaluate from Baseline to the Final/Early Termination visit. ] [ Designated as safety issue: No ]
    Final Visit could occur at any point up to 80 weeks.


Estimated Enrollment: 250
Study Start Date: July 2010
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: adalimumab
adalimumab 80 mg subcutaneous (SC) loading dose at the Baseline study visit followed a week later by 40 mg eow starting at Week 1.
Drug: adalimumab
Subjects will be randomized into one of two arms. Arm 1 will receive adalimumab 80 mg subcutaneous (SC) loading dose at Baseline followed by 40 mg doses eow starting at Week 1. Arm 2 will receive matching placebo. Randomization will be a 1:1 ratio double masked fashion to the treatment groups using baseline immunosuppressant usage as the stratification factor.
Other Name: ABT-D2E7 Humira
Drug: prednisone
Based on the dose of corticosteroids at study entry, a pre-defined taper schedule will be followed that mandates discontinuation of corticosteroid therapy no later than Week 19. Subjects who enter this study on another corticosteroid will be converted to an equivalent dose of prednisone at Baseline.
Placebo Comparator: adalimumab placebo
Placebo 80 mg subcutaneous (SC) loading dose at the Baseline study visit followed a week later by 40 mg placebo injections eow starting at Week 1.
Drug: prednisone
Based on the dose of corticosteroids at study entry, a pre-defined taper schedule will be followed that mandates discontinuation of corticosteroid therapy no later than Week 19. Subjects who enter this study on another corticosteroid will be converted to an equivalent dose of prednisone at Baseline.
Drug: adalimumab placebo
Placebo 80 mg subcutaneous (SC) loading dose at the Baseline study visit followed a week later by 40 mg placebo injections eow starting at Week 1.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject is diagnosed with non-infectious intermediate, posterior, or pan-uveitis.
  • Subject that for >/= 28 days prior to the Baseline visit has inactive disease and is taking >/= 10 mg of oral prednisone to maintain this inactive state and fulfillment of all 3 of the following criteria based on the Investigator's clinical judgment at the Screening and Baseline visits for both eyes:

    • Subject without active, inflammatory chorioretinal and/or inflammatory retinal vascular lesions.
    • Subject with Anterior Chamber Cell grade </= 0.5+ according to Standardization of Uveitis Nomenclature (SUN) criteria.
    • Subject with Vitreous Haze grade </= 0.5+ according to National Eye Institute (NEI)/SUN criteria.
  • Subject is on oral prednisone 10 to 35 mg/day (or oral corticosteroid equivalent) at Baseline and the dose has not been increased in the past 28 days or decreased in the past 14 days.
  • Subject must have a documented history of experiencing at least one disease flare within 18 months of the Screening visit. This flare has to occur during or up to a maximum of 28 days after tapering off the oral corticosteroid therapy.
  • Subjects who do not have previous, active or latent TB. Only one TB test is required to allow the subject in the study. Subjects with either negative PPD (< 5mm of induration) or negative QuantiFERON®-TB Gold test (or 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 confirmed or suspected infectious uveitis, including but not limited to infectious uveitis due to TB, cytomegalovirus (CMV), Lyme disease, toxoplasmosis, Human T-Lymphotropic Virus Type 1 (HTLV-1) infection, Whipple's disease, herpes zoster virus(HZV) 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 (ETDRS [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 a brain MRI within 90 days prior to the Baseline visit.
  • Subject has previous exposure to anti-TNF therapy or any biologic therapy (except intravitreal anti- Vascular endothelial growth factor (VEGF) therapy) with a potential therapeutic impact on non-infectious uveitis.
  • Subject on concomitant immunosuppressive therapy other than methotrexate, cyclosporine, mycophenolate mofetil or an equivalent drug to mycophenolate mofetil (e.g., mycophenolic acid), azathioprine or tacrolimus within 28 days of Baseline or has discontinued an immunosuppressive therapy including methotrexate, cyclosporine, mycophenolate mofetil or an equivalent drug to mycophenolate mofetil (e.g., mycophenolic acid), azathioprine or tacrolimus within 28 days of Baseline.
  • If entering the study on one concomitant immunosuppressive therapy, dose has not been stable for at least 28 days prior to the 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 Retisert® (glucocorticosteroids implant) within 3 years prior to the Baseline visit or has had complications related to the device. Subject has had Retisert® (glucocorticosteroid implant) removed within 90 days prior to the Baseline visit or has had complications related to removal of the device.
  • Subject has received intraocular or periocular corticosteroids within 90 days prior to the 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 cystoid macular edema unless the retinal changes are persistent, residual and stable as defined by the Standardization of Uveitis Nomenclature (SUN) criteria (persistent is > 3 months duration).
  • Subject has received Ozurdex® (dexamethasone implant) within 6 months prior to the Baseline visit.
  • Subject has received intravitreal methotrexate within 90 days 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 on systemic carbonic anhydrase inhibitor within 1 week prior to Screening visit.
  • Subject with a history of scleritis.
  • Subject on cyclophosphamide within 30 days prior to the Baseline visit.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01124838

Contacts
Contact: Andy Payne, PhD 847-938-7795 andy.payne@abbvie.com
Contact: Barry Bittle 610-438-2589 Barry.Bittle@abbvie.com

  Show 124 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Andy Payne AbbVie
  More Information

Additional Information:
No publications provided

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01124838     History of Changes
Other Study ID Numbers: M10-880, 2009-016008-22
Study First Received: May 14, 2010
Last Updated: October 10, 2014
Health Authority: United States: Food and Drug Administration
Austria: Federal Office for Safety in Health Care
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Medicines Agency
Germany: Paul-Ehrlich-Institut
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Israel: Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Portugal: National Pharmacy and Medicines Institute
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Canada: Health Canada
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Switzerland: Swissmedic
Brazil: Ministry of Health
Mexico: Ministry of Health
Czech Republic: State Institute for Drug Control
Greece: Ministry of Health and Welfare
Argentina: Ministry of Health

Keywords provided by AbbVie:
Uveitis

Additional relevant MeSH terms:
Chorioretinitis
Uveitis
Choroid Diseases
Choroiditis
Eye Diseases
Panuveitis
Retinal Diseases
Retinitis
Uveal Diseases
Uveitis, Posterior
Adalimumab
Prednisone
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014