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

This study has been terminated.
(The primary efficacy endpoint was not met)
Sponsor:
Information provided by (Responsible Party):
Lux Biosciences, Inc.
ClinicalTrials.gov Identifier:
NCT00447187
First received: March 12, 2007
Last updated: October 9, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Corneal Diseases
Cornea Transplant
Drug: LX201
Other: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Lux Biosciences, Inc.:

Primary Outcome Measures:
  • graft rejection or graft failure [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 368
Study Start Date: April 2007
Study Completion Date: November 2010
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LX201 0.50 inch implant
LX201 implant contained 30% cyclosporine A by weight and 0.50 inch in length
Drug: LX201

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.

Experimental: LX201 0.75 inch implant
LX201 implant contained 30% cyclosporine A by weight and 0.75 inch by length
Drug: LX201

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.

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00447187

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

Additional Information:
No publications provided

Responsible Party: Lux Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT00447187     History of Changes
Other Study ID Numbers: LX201-01
Study First Received: March 12, 2007
Last Updated: October 9, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Lux Biosciences, Inc.:
corneal graft failure
corneal graft rejection
corneal transplant rejection

Additional relevant MeSH terms:
Corneal Diseases
Eye Diseases
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 23, 2014