A Double-Masked, Placebo-Controlled, Parallel-Group, Multi-Centre, Dose-Ranging Study with an Optional Extension 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: MedDRA version: 8.1Level: LLTClassification code 10046851Term: Uveitis; Subjects with clinically quiescent sight-threatening, non-infectious intermediate-, anterior and intermediate-, posterior- or pan-uveitis requiring systemic immune suppression.

• Registration Number: EUCTR2006-006544-66-DE
• Lead Sponsor: ux Biosciences GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-01-23
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 350

Inclusion Criteria

• A diagnosis of non-infectious intermediate-, anterior and intermediate-, posterior- or pan-uveitis of at least 3 months duration prior to enrollment, requiring treatment during that period to control intraocular inflammatory disease and avoid sight-threatening complications due to inflammation

• Minimum prescribed therapy upon enrollment is one or more of the following:
• Systemic prednisone or equivalent averaging = 10 mg/day
• At least 2 periocular/intravitreal corticosteroid administrations for control of inflammatory disease within the previous 8 months (but not within 6 weeks of randomization)
• At least one, but not more than 2, immunosuppressive drugs from among the following compounds:
• cyclosporine
• tacrolimus
• azathioprine
• mycophenolate mofetil
• mycophenolic acid
• methotrexate

Note: Subjects are not excluded from study entry if they are receiving treatment with topical corticosteroids for control of anterior inflammation.

• The subject’s uveitis is considered clinically quiescent in both eyes on current medications at the time of enrollment. Clinical quiescence means that the prescribed uveitis medications at enrollment have neither been increased in dosage nor augmented for a minimum of 6 weeks prior to enrollment, nor have there been any symptoms or signs of exacerbation of intraocular inflammation during this same 6-week period

• Subjects considered by the Investigator to require immunomodulatory therapy

• Subjects have best corrected visual acuity (BCVA) in the worst involved eye of 20/400 or better (ETDRS logMAR < 1.34)

• Subject does not plan to undergo elective ocular surgery (e.g., cataract extraction) during the course of the study

• At least 18 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) and throughout the extension phase

• 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:
- Be over the age of 60 years
- Be amenorrheic for at least 2 years if aged 45-60
- Have had a hysterectomy and/or bilateral oophorectomy

All other female subjects (including those with tubal ligations) will be considered to be of childbearing potential

• Subjects must weigh at least 38 kg (84 lbs) and no more than 110 kg (242 lbs)
(Note: this restriction is imposed to allow for the masking of treatment assignments.)

• Subjects or their guardians must be:
- Capable of understanding the purpose and risks of the study
- Able to give informed consent (and assent by pediatric subjects, if required)
- Able to comply with the 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

• Uveitis of infectious etiology

• Clinically suspected or confirmed central nervous system or ocular lymphoma

• Primary diagnosis of anterior uveitis

• Evidence of active, uncontrolled non-infectious uveitis

• Uncontrolled glaucoma, as evidenced by an intraocular pressure of > 21 mmHg while on medical therapy

• Subjects with chronic hypotony (less than 6 mmHg)

• A known history or clinical diagnosis of Behçet’s disease

• Local (periocular/intravitreal) administration of corticosteroids within the previous 6 weeks

• Any implantable corticosteroid-eluting device (e.g., Retisert™, Posurdex®, Medidur™, I-vation™ TA intravitreal implant)

• Treatment with 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 30 days or with alemtuzumab within the previous 12 months

• Subjects who have used any drugs or substances known to be strong inhibitors of cytochrome P450 (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 inhibitors, Section 9.6)

• Subjects who have taken any other medications listed in Section 9.6, within the timeframe specified, prior to the first dose

• Recipients of a solid organ transplant

• Subjects with lens opacities or obscured ocular media upon enrollment such that reliable evaluations and grading of the posterior segment cannot be performed

• Presence of an ocular toxoplasmosis scar

• Subjects with 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, HCV)

• Subjects who have a history of or exposure to syphilis or Lyme disease

• Modification of Diet in Renal Disease Study (MDRD) glomerular filtration rate (GFR) < 60 mL/min

• Alanine transaminase (ALT), aspartate transaminase (AST), or gamma-glutamyl transferase (GGT) = 3x upper limit of normal

• Severe anemia (hemoglobin < 6 g/dL), leukopenia (white blood cell count < 2500/mm3), thrombocytopenia (platelet count < 80,000/mm3), polycythemia (hematocrit > 54% [male] or hematocrit > 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 (vitamin E, medium chain triglyceride [MCT] oil, polysorbate 40, ethanol)

• Using a therapy 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

• Subjects with any non-ocular, medically significant co-morbid conditions that impair normal activities, require immunosuppression, or who have a conditio

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this study is to evaluate the safety and efficacy of LX211 as treatment and maintenance therapy in subjects with currently clinically quiescent sight-threatening, non-infectious intermediate-, anterior and intermediate-, posterior- or pan-uveitis requiring systemic immune suppression.;Secondary Objective: None.;Primary end point(s): The primary endpoint is the proportion of subjects who experience inflammatory<br>exacerbation during the 26 weeks of treatment as defined by a clinically significant deterioration in either eye in one or more of the following:<br><br>• vitreous haze: an increase of =2 grades from baseline.<br>• anterior chamber cells: an increase of =2 grades from baseline.<br>• visual acuity: a change of =+0.3 logMAR from baseline in BCVA.