A Double-Masked, Placebo-Controlled, Parallel-Group, Multi-Center, Dose-Ranging Study 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: 8.1Level: LLTClassification code 10046851Term: Uveitis
- Registration Number
- EUCTR2006-006543-31-FR
- Lead Sponsor
- ux Biosciences GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 335
• A documented history of non-infectious intermediate-, anterior and intermediate-, posterior- or panuveitis. 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.
• Currently uncontrolled uveitis for a minimum of 2 weeks on prednisone monotherapy at a dose of =10 mg/day (or equivalent) or despite having received =2 injections of corticosteroid (intravitreal or periocular) for control of disease within the previous six months or subjects for whom oral corticosteroid is contraindicated.
• Subjects who are intolerant of local corticosteroid therapy due to the development of an ocular hypertensive response.
• Grade 2+ or higher for vitreous haze at the time of enrollment.
• Subjects are considered by the investigator to require corticosteroid-sparing therapy. Reasons may include but are not limited to such considerations as exacerbation of previously controlled disease, need for steroid-sparing 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).
• The subject does 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 24 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.
• Subject weighs 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) and to comply with the study requirements.
Are the trial subjects under 18? yes
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.
• Any implantable corticosteroid-eluting device (eg, 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 90 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, Section 9.8).
• Subjects who have taken any other medications listed in Section 9.8, within
the timeframe specified, prior to the first dose.
• Primary diagnosis of anterior uveitis.
• Uncontrolled glaucoma.
• Presence of an ocular toxoplasmosis scar.
• Lens opacities or obscured ocular media upon enrollment such that reliable evaluation and grading of the posterior segment cannot be performed.
• 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.
• Seropositivity for human immunodeficiency virus (HIV).
• Alanine transaminase (ALT), aspartate transaminase (AST), or gammaglutamyl
transferase (GGT) = 3x upper limit of normal (ULN).
• Previous exposure or known contraindication to administration of LX211 (ISA247) or any of its components.
• Recipients of a solid organ transplant.
• Subjects with chronic hypotony (less than 6 mmHg)
• History of clinically defined allergy to any of the constituents of the LX211 formulation (vitamin E, medium chain triglyceride oil, Tween 40, ethanol).
• 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.
• Using a therapy for a condition other than uveitis that would likely affect immune responses or interfere with trial logistics.
• 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).
• Modification of Diet in Renal Disease Study (MDRD) glomerular filtration rate (GFR) < 60 mL/min.
• Severe anemia (hemoglobin < 6 g/dL), leukopenia (WBC < 2500 mm3),
thrombocytopenia (platelet count < 80,000 mm3), polycythemia (Hct > 54%
[male] or Hct > 49% [female]) or clinically significant coagulopathy.
• 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.
• Any non-ocular co-morbid condition that would require immunosuppression or that would likely have an impact on the subject’s ability to comply with the study visit schedule.
• Any current or history of substance abuse, psychiatric disorder or a condition that, in the opinion of the investigator, may invalidate communication.
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 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.;Secondary Objective: None.;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, if 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, change from baseline in graded vitreous haze after 24 weeks of treatment will also be analysed as a primary endpoint.
- Secondary Outcome Measures
Name Time Method