Study to Assess the Efficacy and Safety of LX201 for Prevention of Corneal Allograft Rejection Episodes and Graft Failure in Subjects at Increased Immunological Risk

Inclusion Criteria:

• Subjects are candidates for a corneal transplant and are at increased immunological risk for graft failure, as evidenced by one or more of the following:

  • ≥ 1 quadrant deep corneal vascularization
  • verifiable history of graft failure due to rejection
  • position of graft is < 1 mm from the limbus

Exclusion Criteria:

• Any condition that would greatly increase the risk of non-rejection graft failure such as Stevens-Johnson syndrome, xerophthalmia or severe exposure keratitis.
• Schirmer's test ≤ 5 mm in 1 minute
• Clinical evidence of limbal stem cell deficiency
• History of or active herpes simplex virus keratitis or other acute corneal infection
• Subjects who have had > 3 failed grafts in the study eye
• Uncontrolled glaucoma as evidenced by an intraocular pressure of >21 mmHg while on maximal medical therapy
• Clinically suspected or confirmed ocular lymphoma
• Treatment with a systemic immunosuppressive regimen within the previous 30 days; systemic prednisone (or its equivalent) of ≤ 10 mg daily is, however, permitted.
• Any implantable corticosteroid-eluting device (e.g., Retisert™, Posurdex®, Medidur™, I-vation™ TA intravitreal implant)
• Subjects who periodically require high-dose systemic steroid treatment (e.g., for exacerbation of chronic obstructive pulmonary disease).
• 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
• History 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)
• Previous exposure or known contraindication to administration of cyclosporine
• Recipients of a solid organ transplant
• Currently pregnant or lactating
• Active, extraocular and/or systemic infection requiring the prolonged or chronic use of antimicrobial agents or the presence of active hepatitis A, B or C
• 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
• 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
• Active peptic ulcer disease
• Co-morbid conditions that require immunosuppression