A Multi-Center, Double-Masked, Parallel-Group, Placebo-Controlled Study to Assess the Efficacy and Safety of Voclosporin as Therapy in Subjects with Active Noninfectious Uveitis Involving the Intermediate and/or Posterior Segments of the Eye

• Conditions: on-Infectious Intermediate, Posterior or Pan-uveitis

• Registration Number: EUCTR2010-022128-63-AT
• Lead Sponsor: ux Biosciences, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-11-23
• Last Update Posted: 4 February 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

Eligibility Criteria: Inclusion
I.1.Active noninfectious uveitis involving the intermediate and/or posterior segment (i.e., anterior + intermediate-, intermediate-, posterior- or pan-uveitis) in at least one eye as evidenced by a vitreous haze grade of at least 2+ at the baseline visit (Visit 1). Subjects who also have anterior segment involvement need not be excluded if otherwise qualified.
I.2.Uveitis therapy
Current uveitis therapy must conform to one of the following:
-Prednisone monotherapy at a dose of = 10 mg/day and = 40 mg/day (or equivalent dose of another corticosteroid) for at least 2 weeks prior to the baseline visit (Visit 1).
-Prednisone, at any dose = 40 mg/day (or equivalent dose of another corticosteroid), in addition to one immunosuppressive agent from among cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid or methotrexate for at least 2 weeks prior to the baseline visit (Visit 1).
?Receiving monotherapy with azathioprine, mycophenolate mofetil, mycophenolic acid or methotrexate for at least 2 weeks prior to randomization.
?Not receiving systemic therapy and not receiving corticosteroid therapy (systemic or local) and for whom systemic or local corticosteroid therapy is medically inappropriate or refused by the patient.

-N.B: All immunosuppressive therapy (excluding systemic corticosteroids) must be discontinued by the evening prior to the baseline visit (Visit 1).
I.3.Considered by the Investigator to require systemic immunosuppressive therapy.
I.4.A minimum ability to count fingers at a distance of 30 cm (1 foot) with each eye at the baseline visit (Visit 1).
I.5.At least 18 years of age.
I.6. Subjects, whether male or female, with reproductive potential and who are sexually active must agree to use double-barrier contraception methods BEFORE beginning study drug therapy, for the duration of the study (minimum of 24 weeks), and for 6 weeks following completion of study drug.
I.7.Women of childbearing potential must have a negative urine pregnancy test within 48 hours prior to subject’s assignment to study treatment at the baseline visit (Visit 1). All female subjects (including those with tubal ligations) will be considered to be of childbearing potential unless one or more of the following criteria are met:
-Over the age of 60 years.
-Amenorrheic for at least 2 years if age 45-60 years.
-Have had a hysterectomy and/or bilateral oophorectomy.
I.8.Subjects must be:
-Capable of understanding the purpose and risks of the study.
-Able to give written informed consent.
-Able to comply with all study requirements.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

E1. Ocular Disease/Conditions
The following conditions are exclusionary if present:
E1.1.Uveitis limited to only the anterior segment of the study eye.
E1.2.Confirmed or suspected infectious uveitis in either eye, including but not limited to infectious uveitis due to tuberculosis, cytomegalovirus, Lyme disease, toxoplasmosis, Human T-Lymphotropic Virus Type 1 (HTLV-1), Whipple’s disease, herpes zoster virus (HZV), and herpes simplex virus (HSV) or history of other ocular herpetic infection; Fuchs heterochromic iridocyclitis.
E1.3.Presence of an ocular toxoplasmosis scar or suspected active infection in either eye.
E1.4.Active infection (i.e. bacterial, viral, parasitic or fungal) in either eye.
E1.5.Serpiginous choroidopathy in either eye.
E1.6.Active inflammatory lesions or vasculitis involving the central macula within 1,000 microns of the fovea (either eye).
E1.7.History of central serous chorioretinopathy in either eye.
E1.8.Proliferative or severe non-proliferative diabetic retinopathy in either eye.
E1.9.Neovascular/exudative/wet age-related macular degeneration in either eye.
E1.10.Abnormality of vitreoretinal interface (i.e., vitreomacular traction, epiretinal membranes, etc.) thought by the Investigator to interfere with measurement of macular thickness or with the potential for macular structural damage independent of the inflammatory process in the study eye.
E1.11.Clinically suspected or confirmed ocular lymphoma (either eye).
E1.12.Obscured ocular media (e.g., corneal scars, lens opacities, vitreous abnormalities, etc.) in the study eye at baseline (Visit 1) such that reliable evaluations and grading of either the intermediate or posterior segment cannot be performed.
E1.13.Any other ocular disease in the study eye that can interfere with the diagnosis or assessment of disease progression.
E1.14.Monocular (no light perception or anophthalmic in fellow eye).
E1.15.Intraocular pressure of < 6 mmHg or > 21 mmHg in either eye at the baseline visit (Visit 1).
E1.16.Chronic hypotony (intraocular pressure less than 6 mmHg or clinical signs such as choroidals, choroidal, or corneal folds) or pre-phthisical state (e.g., scleral thickening on ultrasonography, decreasing globe size) in either eye.
E1.17.Contraindication to pupil dilation in either eye.
E1.18.A likely need for ocular surgery (e.g., cataract extraction, laser treatment) in the study eye during the period of study participation.
E2. Specific Prior and Current Treatments (for details please refer to protocol)
E3. Specific Extra-ocular Conditions (for details please refer to protocol)
E4. Specific Laboratory, Blood Pressure and ECG Evaluations (for details please refer to protocol)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to assess the safety and efficacy of voclosporin as therapy in subjects with active noninfectious uveitis involving the intermediate and/or posterior ocular segments. ;Secondary Objective: Primary Endpoint: The change from baseline in graded vitreous haze in the study eye at 12 weeks of therapy or at the time of treatment failure, if earlier.<br>Secondary Endpoints:<br>1. Time to treatment failure or inadequate response to therapy.<br>2. Daily mean systemic corticosteroid dose used during Weeks 12-24. <br>2. Change from baseline in the composite score of the National Eye Institute (NEI) Visual Function Questionnaire-25 (VFQ-25) at Week 24.<br>;Primary end point(s): The change from baseline in graded vitreous haze in the study eye at 12 weeks of therapy or at the time of treatment failure, if earlier.