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

NCT ID: NCT00447187

Last Updated: 2012-10-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

368 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-04-30

Study Completion Date

2010-11-30

Brief Summary

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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

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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.

Conditions

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Corneal Diseases Cornea Transplant

Keywords

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corneal graft failure corneal graft rejection corneal transplant rejection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants

Study Groups

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LX201 0.50 inch implant

LX201 implant contained 30% cyclosporine A by weight and 0.50 inch in length

Group Type EXPERIMENTAL

LX201

Intervention Type DRUG

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.

LX201 0.75 inch implant

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

Group Type EXPERIMENTAL

LX201

Intervention Type DRUG

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 0.75 inch implant

Silicone implant not containing cyclosporine A, 0.75 inch in length

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

The placebo was a silicone implant 0.75 inch in length. It contained no cyclosporine A

Interventions

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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.

Intervention Type DRUG

Placebo

The placebo was a silicone implant 0.75 inch in length. It contained no cyclosporine A

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lux Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eddy Anglade, MD

Role: STUDY_CHAIR

Chief Medical Officer, Lux Biosciences, Inc.

Locations

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Cornea Consultants of Arizona

Phoenix, Arizona, United States

Site Status

Loma Linda University Health Care

Loma Linda, California, United States

Site Status

USC Doheny Eye Institute

Los Angeles, California, United States

Site Status

Bascom Palmer Eye Institute

Miami, Florida, United States

Site Status

Emory Eye Center

Atlanta, Georgia, United States

Site Status

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Price Vision Group

Indianapolis, Indiana, United States

Site Status

The Eye Center at Union Memorial Hospital

Baltimore, Maryland, United States

Site Status

Wilmer Eye Institute, Cornea Service

Baltimore, Maryland, United States

Site Status

New England Eye Center

Boston, Massachusetts, United States

Site Status

W.K. Kellogg Eye Center - University of Michigan

Ann Arbor, Michigan, United States

Site Status

MN Eye Consultants, P.A.

Bloomington, Minnesota, United States

Site Status

Tauber Eye Center

Kansas City, Missouri, United States

Site Status

Ophthalmology Associates

St Louis, Missouri, United States

Site Status

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

Newark, New Jersey, United States

Site Status

New York Eye and Ear Infirmary

New York, New York, United States

Site Status

Mount Sinai School of Medicine

New York, New York, United States

Site Status

Ophthalmic Consultants of Long Island

Rockville Centre, New York, United States

Site Status

Cornea Consultants of Albany

Slingerlands, New York, United States

Site Status

Duke University Eye Center

Durham, North Carolina, United States

Site Status

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

Cornea Associates of Texas

Dallas, Texas, United States

Site Status

Virginia Eye Consultants

Norfolk, Virginia, United States

Site Status

Eye Associates NW

Seattle, Washington, United States

Site Status

Augenklinik, Universitat Erlangen-Nurnberg

Erlangen, , Germany

Site Status

Cornea Bank, Universitätsklinikum Essen

Essen, , Germany

Site Status

Klinik fuer Ophthalmologie Campus Kiel

Kiel, , Germany

Site Status

Ludwig Maximilians Universität

München, , Germany

Site Status

Augenklinik der Technischen Universität München

München, , Germany

Site Status

Augenklinik Wuerzburg

Würzburg, , Germany

Site Status

Countries

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United States Germany

References

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Bock F, Matthaei M, Reinhard T, Bohringer D, Christoph J, Ganslandt T, Cursiefen C. High-dose subconjunctival cyclosporine a implants do not affect corneal neovascularization after high-risk keratoplasty. Ophthalmology. 2014 Sep;121(9):1677-82. doi: 10.1016/j.ophtha.2014.03.016. Epub 2014 Apr 26.

Reference Type DERIVED
PMID: 24780407 (View on PubMed)

Related Links

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Other Identifiers

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LX201-01

Identifier Type: -

Identifier Source: org_study_id