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 - Full Text View

Sponsored by:	Lux Biosciences, Inc.
Information provided by:	Lux Biosciences, Inc.
ClinicalTrials.gov Identifier:	NCT00447187

Purpose

This is 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	Phase III

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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

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

Primary Outcome Measures:

immunological rejection
graft loss

Secondary Outcome Measures:

vision
quality of life

Estimated Enrollment:	175
Study Start Date:	March 2007
Estimated Study Completion Date:	January 2009
Estimated Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Detailed Description:

Did you know?

The cornea is one of the most frequently transplanted tissues in the United States. According to the Eye Bank of America, over 30,000 transplants are performed in the United States each year.
Corneal grafts can fail. Rates for corneal graft failure after transplantation have not improved over the last 40 years
There are no FDA approved treatments for the prevention or treatment of rejection of corneal grafts.

Studies report that 10% of corneal grafts fail within 2 years. However, for high-risk patients, the chances of graft failure within 2 years is as high as 40-65%. Even before graft loss actually occurs, rejection episodes may damage cells in the cornea, often leading to a decrease in visual clarity.

Causes for high risk for having a graft rejection include having had a previous graft failure or having blood vessels in the cornea (a normal cornea has no blood vessels).

Lux Biosciences, Inc. is currently investigating the use of a new treatment, LX201, to prevent the transplanted cornea from being rejected by the body's immune system. LX201 is implanted in the transparent membrane covering the white of the eye under the eyelid via a simple procedure. LX201 is made of silicone, a substance that has long been used safely in the eye. LX201 releases a medication called cyclosporine at steady doses over the course of a year. Cyclosporine, in the form of eyedrops, is approved by FDA for use in dry eye syndrome. Cyclosporine has also been used in oral form for over 20 years to help prevent the rejection of transplanted organs by the body. Therefore, although its use in the Lux research studies is investigational, the drug itself has a long history of use in man.

The presumed advantage of LX201 is that, by releasing cyclosporine from within the eye, high levels of cyclosporine are maintained in the surrounding ocular tissues. These levels are higher than those that can be achieved by oral cyclosporine or cyclosporine as eye drops. It is believed that these higher doses applied in a sustained fashion are needed for effective prevention of cornea transplant rejection. Importantly, the cyclosporine from the implant does not enter the blood system, so the significant side effects (for example, kidney and liver dysfunction, high blood pressure, and increased risk of infection) often associated with cyclosporine use are avoided.

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

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

Contacts

Contact: Cathy Stein-Izsak, PhD

clinicaltrials@luxbio.com

Show 30 Study Locations

Sponsors and Collaborators

Lux Biosciences, Inc.

More Information

Related Info This link exits the ClinicalTrials.gov site

Study ID Numbers:	LX201-01
Study First Received:	March 12, 2007
Last Updated:	July 8, 2008
ClinicalTrials.gov Identifier:	NCT00447187
Health Authority:	United States: Food and Drug Administration

Keywords provided by Lux Biosciences, Inc.:

corneal graft failure
corneal graft rejection
corneal transplant rejection

Study placed in the following topic categories:

Corneal Diseases
Eye Diseases

ClinicalTrials.gov processed this record on January 16, 2009