A Double-Masked, Placebo-Controlled, Parallel-Group, Multi-Center, Dose-Ranging Study with an Optional Extension to Assess the Efficacy and Safety of LX211 as Therapy in Subjects with Active Sight Threatening, Non-Infectious Intermediate-, Anterior and Intermediate-, Posterior-, or Pan-Uveitis.
- Conditions
- Subjects with active sight-threatening, non-infectious intermediate-, anterior and intermediate-, posterior- or pan-uveitis.MedDRA version: 8.1 Level: LLT Classification code 10046851 Term: Uveitis
- Registration Number
- EUCTR2006-006543-31-GB
- Lead Sponsor
- ux Biosciences GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 335
• Subjects with a documented history of non-infectious intermediate-, anterior and intermediate-, posterior- or pan-uveitis
• Uncontrolled uveitis, as evidenced by Grade 2+ or higher vitreous haze, in at least one eye for = 2 weeks prior to randomization.
• Current uveitis therapy must conform to one of the following:
• Prednisone monotherapy at a dose of = 10 mg/day (or equivalent) for = 2 weeks prior to randomization
• Have received = 2 injections of corticosteroid (intravitreal or periocular) for control of disease within the past 8 months, but not within 2 weeks of randomization; subjects may also be receiving systemic corticosteroid therapy
• Receiving monotherapy with azathioprine, mycophenolate mofetil, mycophenolic acid or methotrexate for at least 2 weeks prior to randomization
• Receiving prednisone in addition to one immunomodulatory agent from among cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, mycophenolic acid and methotrexate for at least 2 weeks prior to randomization
• Subjects for whom corticosteroid therapy (systemic or local) is medically inappropriate or who refuse corticosteroid therapy
• Considered by the Investigator to require immunomodulatory therapy
• Subjects do not plan to undergo elective ocular surgery (e.g., cataract extraction) during the study
• A minimum ability to count fingers at a distance of 30 cm (1 foot) using the study eye
• 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 24 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 age 45-60 years
• 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
• Uveitis of infectious etiology
• Clinically suspected or confirmed central nervous system or ocular lymphoma
• Primary diagnosis of anterior uveitis
• Uncontrolled glaucoma as evidenced by an intraocular pressure of >21 mmHg while on medical therapy
• Subjects with chronic hypotony (less than 6 mmHg)
• 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 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 inhibitors, Section 9.8)
• Subjects who have taken any other medications listed in Section 9.8, within the timeframe specified, prior to the first dose
• Presence of an ocular toxoplasmosis scar
• 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
• Subjects with a known history or clinical diagnosis of herpes zoster or varicella infection within 6 weeks before enrollment or chicken pox exposure within 21 days before enrollment
• 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 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
• Participating in another clinical trial with an investigational agent in the 30 days prior to study participation 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 impa
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: The objective of this study is to assess the safety and efficacy of LX211 as<br> therapy in subjects with active sight-threatening, non-infectious intermediate-,<br> anterior and intermediate-, posterior-, or pan- uveitis.<br> ;Secondary Objective: None.;<br> Primary end point(s): The primary endpoint is the mean change from baseline in graded vitreous haze after 16 weeks of therapy or at time of rescue, it earlier. Subjects who experience either an increase of at least 1 grade from baseline at Visit 3 or show no improvement from baseline by Visit 4 are to receive rescue therapy.<br><br> If statistical significance is achieved for vitreous haze at 16 weeks, then mean change from baseline in graded vitreous haze after 24 weeks of therapy or at time of rescue, if earlier, will also be analyzed as a primary endpoint.<br>
- Secondary Outcome Measures
Name Time Method