A Double-Masked, Placebo-Controlled, Multi-Centre, Parallel Group, Dose-Ranging Study to Assess the Efficacy and Safety of LX211 as Therapy in Subjects with Clinically Quiescent Sight Threatening, Non-Infectious Intermediate-, Anterior and Intermediate-, Posterior-, or Pan-Uveitis.
- Conditions
- Subjects with clinically quiescent sight threatening, non-infectious, intermediate-, anterior and intermediate-, posterior- or pan-uveitis.MedDRA version: 8.1Level: LLTClassification code 10046851Term: Uveitis
- Registration Number
- EUCTR2006-006544-66-AT
- Lead Sponsor
- ux Biosciences GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 350
• A diagnosis of non-infectious intermediate-, anterior and intermediateposterior-
or pan- uveitis of at least three months duration prior to enrollment, requiring treatment during that period to control intraocular inflammatory disease and avoid sight-threatening complications due to inflammation. Subjects are anticipated to have, but are not restricted to, the following conditions: intermediate uveitis of the pars planitis subtype, sarcoidosis, the Vogt-Koyanagi-Harada (VKH) syndrome, birdshot retinochoroidopathy, retinal vasculitis, sympathetic ophthalmia and multifocal choroiditis with panuveitis
• Minimum prescribed therapy upon enrollment is either a dose averaging = 10 mg/day of systemic prednisone or equivalent or a more intensive immunosuppression regimen (e.g. corticosteroid combined with a
corticosteroid-sparing agent) and/or repeated periocular/intravitreal corticosteroid administration (i.e. = 2 administrations within the previous 6 months) for control of inflammatory disease. More intensive regimens may include one additional immunosuppressive drug from among the following (or related) compounds:
- cyclosporine
- tacrolimus
- azathioprine
- mycophenolate mofetil
- methotrexate
• Subjects who are intolerant of local corticosteroid therapy due to the
development of an ocular hypertensive episode
• Subjects may also enter the study if they are receiving treatment with topical
corticosteroids for control of anterior inflammation
• Subjects may also enter the study if they are receiving treatment with a single
immunomodulatory drug for uveitis control
• The subject’s uveitis is considered clinically quiescent on current medications
at the time of enrollment. Clinical quiescence means that the prescribed
dosage(s) for their current uveitis medications at enrollment have neither
been increased in the 6 weeks prior to enrollment, nor there have been any
symptoms, signs or history of exacerbation of intraocular inflammation during
this same 6-week period
• Subjects are considered by the investigator to require corticosteroid-sparing
therapy. Reasons may include such considerations as need for steroidsparing
therapy, corticosteroid-intolerance, history of diabetes, adverse experiences with current therapy or conditions for which immunosuppressive therapy is used typically (e.g. posterior uveitides, birdshot retinochoroidopathy, multifocal choroiditis with panuveitis)
• Subjects have BCVA in the worst involved eye of 20/400 or better (ETDRS
logMAR < 1.34)
• Subjects do not plan to undergo elective ocular surgery (e.g., cataract
extraction) during the course of the study
• At least 13 years of age
• Subjects, whether male or female, with reproductive potential and who are
sexually active agree to use double-barrier contraception methods throughout
the course of the study (minimum of 26 weeks)
• Women of childbearing potential must have a negative urine pregnancy test
(UPT) within 48 hours prior to starting study drug and must not be lactating
Female subjects of non-childbearing potential must meet at least one of the
following criteria:
1. Postmenopausal females, defined as:
a. Females over the age of 60 years.
b. Females who are 45 to 60 years of age must be
amenorrheic for at least 2 years.
2. Females who had a hysterectomy and/or bilateral oophorectomy.
All other female subjects (including females with tubal ligations) will be
considered to be of childbearing potential.
• Subjects weigh at least 38 kg (84 lbs) and no more than 11
• Uveitis of infectious etiology
• Clinically suspected or confirmed central nervous system or ocular lymphoma
• A primary diagnosis of anterior uveitis
• Evidence of active, uncontrolled non-infectious uveitis
• Uncontrolled glaucoma
• A history or diagnosis of Behçet’s disease (since tapering or withdrawal of concomitant immunosuppressive medications is not a usual standard-of-care
for Behçet’s subjects)
• Local (periocular/intravitreal) administration of corticosteroids within the
previous 6 weeks
• Any implantable corticosteroid-eluting device (eg, Retisert™, Posurdex®,
Medidur™, I-vation™ TA intravitreal implant)
• An immune suppression regimen that includes an alkylating agent within the
previous 90 days
• Subjects who have received treatment with a monoclonal antibody or any
other biologic therapy within the previous 90 days or with alemtuzumab within
the previous 12 months
• Subjects who have used any drugs or substances known to be strong
inhibitors of CYP 3A4/5 enzymes within 7 days of the first dose, or grapefruit
juice and star fruit within 24 hours of the first dose (listed in table of CYP
3A4/5, Section 9.7)
• Subjects who have taken any other medications listed in Section 9.7, within
the timeframe specified, prior to the first dose
• Recipients of a solid organ transplant
• Subjects with chronic hypotony (less than 6 mmHg)
• Subjects with lens opacities or obscured ocular media upon enrollment such
that reliable evaluation and grading of the posterior segment cannot be
performed
• Presence of an ocular toxoplasmosis scar
• A known history or clinical diagnosis of herpes zoster or varicella infection
within 6 weeks prior to enrollment, or chicken pox exposure within 21 days
before enrollment
• Subjects with diabetes mellitus that is inadequately controlled
• Active, extraocular infection requiring the prolonged or chronic use of
antimicrobial agents or the presence of active hepatitis A, B or C virus (HAV,
HBV, HCB)
• Subjects who have a history of or exposure to syphilis, Lyme , or
toxoplasmosis
• Modification of Diet in Renal Disease Study (MDRD) glomerular filtration rate
(GFR) < 60 mL/min
• Alanine transaminase (ALT), aspartate transaminase (AST), or gammaglutamyl
transferase (GGT) = 3x upper limit of normal (ULN)
• Severe anemia (hemoglobin < 6 g/dL), leukopenia (white blood cell count[WBC] < 2500 mm3), thrombocytopenia (platelet count < 80,000 mm3),
polycythemia (hematocrit [Hct] > 54% [male] or Hct > 49% [female]) or
clinically significant coagulopathy
• Seropositivity for human immunodeficiency virus (HIV)
• Current malignancy or a history of malignancy (within the previous 5 years)
except non-metastatic basal or squamous cell carcinoma of the skin or
carcinoma-in-situ of the cervix that has been treated successfully
• Previous exposure or known contraindication to administration of LX211
(ISA247) or any of its components
• History of clinically defined allergy to any of the constituents of the LX211
formulation (vitamin E, medium chain triglyceride [MCT] oil, Tween 40,
ethanol)
• Using a therapy for a condition other than uveitis that would likely affect
immune responses or interfere with trial logistics
• Currently enrolled in another clinical therapeutic trial or who have received
any investigational therapy within the 30 days prior to enrollment and/or has
not recovered from any reversible effects or side effects of prior
investigational agent
• Subject with any non-ocular, medically significant co-morbid con
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method