Clinical trial NCT00447187: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Corneal Diseases
Cornea Transplant
Keywords: corneal graft failure
corneal graft rejection
corneal transplant rejection
Lead sponsor: Lux Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2007-03-14
Enrollment: 368
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 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: 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 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

Primary outcomes:
measure: graft 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:
citation: 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.