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

Study Overview
=================
Brief Summary
-----------------
This was a pivotal trial to determine whether LX201 reduces the likelihood of a graft rejection episode following corneal transplantation in patients at high immunological risk for rejection.

Detailed Description
-----------------
LX201 was a novel sustained-release silicone implant containing 30% cyclosporine A by weight. LX201 was intended for surgical episcleral placement in the eye. The study was a Phase 2/3, multi-center, placebo-controlled, randomized, parallel-group, dose-ranging study of LX201 for prevention of corneal allograft rejection or graft failure following penetrating keratoplasty with LX201 implantation. Subjects were to be followed in an outpatient setting for safety and efficacy at 4-6 week intervals for 52 weeks following transplantation surgery. After Visit 12 (Week 52), subjects in the USA and India with the implant in the study eye were to be followed for safety at least once per year for a 2-year period or until time of implant removal. For subjects in the USA and India, if the implant was removed at any time prior to the 3 year safety follow-up, the subject was to have a final safety follow up visit at 3 months post removal. In Germany, the implant was to be removed at Week 52 with a 3-month safety follow-up period after removal.

Official Title
-----------------
A Multi-center, Placebo-Controlled, Randomized, Parallel Group, Dose-Ranging Study to Assess the Efficacy and Safety of LX201 for Prevention of Corneal Allograft Rejection Episodes and Graft Failure Following Penetrating Keratoplasty With LX201 Implantation in Subjects Who Are at Increased Immunological Risk

Conditions
-----------------
Corneal Diseases, Cornea Transplant

Intervention / Treatment
-----------------
* Drug: LX201
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LX201 0.50 inch implant<br>LX201 implant contained 30% cyclosporine A by weight and 0.50 inch in length | Drug: LX201<br>* LX201 is a novel sustained-release silicone implant containing 30% cyclosporine A by weight. LX201 was available in two different lengths, 0.50 and 0.75 inch. Each implant was 0.08 inch wide and 0.04 inch in height. The implants were flat on one side (the posterior surface, which is applied to the episclera) and the anterior surface and ends were rounded.<br>|
| Experimental: LX201 0.75 inch implant<br>LX201 implant contained 30% cyclosporine A by weight and 0.75 inch by length | Drug: LX201<br>* LX201 is a novel sustained-release silicone implant containing 30% cyclosporine A by weight. LX201 was available in two different lengths, 0.50 and 0.75 inch. Each implant was 0.08 inch wide and 0.04 inch in height. The implants were flat on one side (the posterior surface, which is applied to the episclera) and the anterior surface and ends were rounded.<br>|
| Placebo Comparator: Placebo 0.75 inch implant<br>Silicone implant not containing cyclosporine A, 0.75 inch in length | Other: Placebo<br>* The placebo was a silicone implant 0.75 inch in length. It contained no cyclosporine A<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| graft rejection or graft failure |  | 52 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
corneal graft failure, corneal graft rejection, corneal transplant rejection