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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

Phase 3
Terminated
Conditions
Corneal Transplantation
Corneal Graft Rejection
Interventions
Other: Placebo
Registration Number
NCT00447642
Lead Sponsor
Lux Biosciences, Inc.
Brief Summary

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.

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
122
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo 0.75 inch implantPlaceboSilicone implant not containing cyclosporine A, 0.75 inch in length
LX201 0.50 inch implantLX201LX201 implant contained 30% cyclosporine A by weight and 0.50 inch in length
LX201 0.75 inch implantLX201LX201 implant contained 30% cyclosporine A by weight and 0.75 inch by length
Primary Outcome Measures
NameTimeMethod
prevention of corneal allograft rejection or graft failure52 weeks
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (30)

Wilmer Eye Institute, Cornea Service

🇺🇸

Baltimore, Maryland, United States

Bascom Palmer Eye Institute

🇺🇸

Miami, Florida, United States

Duke University Eye Center

🇺🇸

Durham, North Carolina, United States

University Hospitals Case Medical Center

🇺🇸

Cleveland, Ohio, United States

Price Vision Group

🇺🇸

Indianapolis, Indiana, United States

Eye Associates NW

🇺🇸

Seattle, Washington, United States

University of Illinois at Chicago

🇺🇸

Chicago, Illinois, United States

New England Eye Center

🇺🇸

Boston, Massachusetts, United States

Tauber Eye Center

🇺🇸

Kansas City, Missouri, United States

Emory Eye Center

🇺🇸

Atlanta, Georgia, United States

Mount Sinai School of Medicine

🇺🇸

New York, New York, United States

Cornea Consultants of Arizona

🇺🇸

Phoenix, Arizona, United States

Virginia Eye Consultants

🇺🇸

Norfolk, Virginia, United States

Klinik fuer Ophthalmologie Campus Kiel

🇩🇪

Kiel, Germany

Augenklinik Wuerzburg

🇩🇪

Wuerzburg, Germany

Ophthalmology Associates

🇺🇸

St. Louis, Missouri, United States

Cornea Consultants of Albany

🇺🇸

Slingerlands, New York, United States

W.K. Kellogg Eye Center - University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

UMDNJ - New Jersey Medical School Institute of Ophthalmology and Visual Science

🇺🇸

Newark, New Jersey, United States

Loma Linda University Health Care

🇺🇸

Loma Linda, California, United States

USC Doheny Eye Institute

🇺🇸

Los Angeles, California, United States

The Eye Center at Union Memorial Hospital

🇺🇸

Baltimore, Maryland, United States

MN Eye Consultants, P.A.

🇺🇸

Bloomington, Minnesota, United States

Augenklinik, Universitat Erlangen-Nurnberg

🇩🇪

Erlangen, Germany

Cornea Bank, Universitätsklinikum Essen

🇩🇪

Essen, Germany

Cornea Associates of Texas

🇺🇸

Dallas, Texas, United States

New York Eye and Ear Infirmary

🇺🇸

New York, New York, United States

Ophthalmic Consultants of Long Island

🇺🇸

Rockville Center, New York, United States

Ludwig Maximilians Universität

🇩🇪

Muenchen, Germany

Augenklinik der Technischen Universität München

🇩🇪

München, Germany

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