Clinical trial NCT00447642: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Corneal Transplantation
Corneal Graft Rejection
Keywords: immunology
cornea
allograft
corneal allograft rejection
graft failure
Lead sponsor: Lux Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2007-03-15
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: prevention of corneal allograft rejection or graft failure
timeFrame: 52 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Cornea Consultants of Arizona
state: Arizona
city: Loma Linda
country: United States
facility: Loma Linda University Health Care
state: California
city: Los Angeles
country: United States
facility: USC Doheny Eye Institute
state: California
city: Miami
country: United States
facility: Bascom Palmer Eye Institute
state: Florida
city: Atlanta
country: United States
facility: Emory Eye Center
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Price Vision Group
state: Indiana
city: Baltimore
country: United States
facility: The Eye Center at Union Memorial Hospital
state: Maryland
city: Baltimore
country: United States
facility: Wilmer Eye Institute, Cornea Service
state: Maryland
city: Boston
country: United States
facility: New England Eye Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: W.K. Kellogg Eye Center - University of Michigan
state: Michigan
city: Bloomington
country: United States
facility: MN Eye Consultants, P.A.
state: Minnesota
city: Kansas City
country: United States
facility: Tauber Eye Center
state: Missouri
city: St. Louis
country: United States
facility: Ophthalmology Associates
state: Missouri
city: Newark
country: United States
facility: UMDNJ - New Jersey Medical School Institute of Ophthalmology and Visual Science
state: New Jersey
city: New York
country: United States
facility: New York Eye and Ear Infirmary
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Rockville Center
country: United States
facility: Ophthalmic Consultants of Long Island
state: New York
city: Slingerlands
country: United States
facility: Cornea Consultants of Albany
state: New York
city: Durham
country: United States
facility: Duke University Eye Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Dallas
country: United States
facility: Cornea Associates of Texas
state: Texas
city: Norfolk
country: United States
facility: Virginia Eye Consultants
state: Virginia
city: Seattle
country: United States
facility: Eye Associates NW
state: Washington
city: Erlangen
country: Germany
facility: Augenklinik, Universitat Erlangen-Nurnberg
city: Essen
country: Germany
facility: Cornea Bank, Universitätsklinikum Essen
city: Kiel
country: Germany
facility: Klinik fuer Ophthalmologie Campus Kiel
city: Muenchen
country: Germany
facility: Ludwig Maximilians Universität
city: München
country: Germany
facility: Augenklinik der Technischen Universität München
city: Wuerzburg
country: Germany
facility: Augenklinik Wuerzburg
Study officials:
affiliation: Chief Medical Officer, Lux Biosciences, Inc.
name: Eddy Anglade, MD
role: STUDY_CHAIR
References: