Study to Assess LX201 for Prevention of Corneal Allograft Rejection or Graft Failure in Subjects Who Have Experienced One or More Rejection Episodes Following Penetrating Keratoplasty

A Multi-center, Placebo-Controlled, Randomized, Parallel-Group, Dose-Ranging Study to Assess the Efficacy and Safety of LX201 Implantation for the Prevention of Corneal Allograft Rejection Episodes or Graft Failure in Subjects Who Have Experienced One or More Rejection Episodes Following Penetrating Keratoplasty

This study will evaluate the use of LX201 to prevent future graft rejection episodes and/or graft failure in patients who have undergone corneal transplantation and who have recently experienced a rejection episode due to an immune response.

Study Overview

• Status: Terminated
• Conditions: Corneal Transplantation; Corneal Graft Rejection
• Intervention / Treatment: Other: Placebo; Drug: LX201

Detailed Description

LX201 was a novel sustained-release silicone implant containing 30% cyclosporine A by weight. LX201 is 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 in subjects who have had one or more rejection episodes following penetrating keratoplasty.

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. In Germany, the implant was to be removed at Week 52 with a 3-month safety follow-up period after removal.

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Erlangen, Germany, 91054
    • Augenklinik, Universitat Erlangen-Nurnberg
  • Essen, Germany, 45122
    • Cornea Bank, Universitätsklinikum Essen
  • Kiel, Germany, 24105
    • Klinik fuer Ophthalmologie Campus Kiel
  • Muenchen, Germany, 80336
    • Ludwig Maximilians Universität
  • München, Germany, 81675
    • Augenklinik der Technischen Universität München
  • Wuerzburg, Germany, 97080
    • Augenklinik Wuerzburg
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Cornea Consultants of Arizona
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health Care
    • Los Angeles, California, United States, 90033
      • USC Doheny Eye Institute
  • Florida
    • Miami, Florida, United States, 33136
      • Bascom Palmer Eye Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Eye Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Price Vision Group
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • The Eye Center at Union Memorial Hospital
    • Baltimore, Maryland, United States, 21287
      • Wilmer Eye Institute, Cornea Service
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • New England Eye Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • W.K. Kellogg Eye Center - University of Michigan
  • Minnesota
    • Bloomington, Minnesota, United States, 55431
      • MN Eye Consultants, P.A.
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Tauber Eye Center
    • St. Louis, Missouri, United States, 63141
      • Ophthalmology Associates
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • UMDNJ - New Jersey Medical School Institute of Ophthalmology and Visual Science
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10003
      • New York Eye and Ear Infirmary
    • Rockville Center, New York, United States, 11570
      • Ophthalmic Consultants of Long Island
    • Slingerlands, New York, United States, 12159
      • Cornea Consultants of Albany
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Eye Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Cornea Associates of Texas
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Eye Consultants
  • Washington
    • Seattle, Washington, United States, 98104
      • Eye Associates NW

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who, within 6 months prior to study randomization, have experienced 1 or more corneal allograft rejection episodes following penetrating keratoplasty
• Must be on a stable medical regimen for at least 14 days at the time of randomization into the study
• Conjunctiva must be suitable for implantation with the study device

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 ipsilateral 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™ triamcinolone acetonide [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 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
• 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LX201 0.50 inch implant; LX201 implant contained 30% cyclosporine A by weight and 0.50 inch in length	Drug: LX201; LX201 was 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 is 0.08 inch wide and 0.04 inch in height. The implants are flat on one side (the posterior surface, which is applied to the episclera) and the anterior surface and ends were rounded.
Experimental: LX201 0.75 inch implant; LX201 implant contained 30% cyclosporine A by weight and 0.75 inch by length	Drug: LX201; LX201 was 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 is 0.08 inch wide and 0.04 inch in height. The implants are flat on one side (the posterior surface, which is applied to the episclera) and the anterior surface and ends were rounded.
Placebo Comparator: Placebo 0.75 inch implant; Silicone implant not containing cyclosporine A, 0.75 inch in length	Other: Placebo; The placebo was a silicone implant 0.75 inch in length. It contained no cyclosporine A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
prevention of corneal allograft rejection or graft failure	52 weeks

Collaborators and Investigators

• Sponsor: Lux Biosciences, Inc.
• Investigators: Study Chair: Eddy Anglade, MD, Chief Medical Officer, Lux Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: March 13, 2007
• First Submitted That Met QC Criteria: March 13, 2007
• First Posted (Estimate): March 15, 2007

Study Record Updates

• Last Update Posted (Estimate): October 11, 2012
• Last Update Submitted That Met QC Criteria: October 9, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: allograft; cornea; immunology; graft failure; corneal allograft rejection
• Other Study ID Numbers: LX201-02