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 - Full Text View

Sponsored by:	Lux Biosciences, Inc.
Information provided by:	Lux Biosciences, Inc.
ClinicalTrials.gov Identifier:	NCT00447642

Purpose

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.

Condition	Intervention	Phase
Corneal Transplantation Corneal Graft Rejection	Drug: LX201 Other: 0.75" Placebo Implant	Phase III

Drug Information available for: Cyclosporin Cyclosporine

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 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

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

Primary Outcome Measures:

immunological graft rejection episode or graft failure [ Time Frame: within 52 weeks post implant placement ]

Secondary Outcome Measures:

corneal neovascularization [ Time Frame: 24 and 52 weeks post implant placement ]

Estimated Enrollment:	240
Study Start Date:	March 2007
Estimated Study Completion Date:	March 2009

Arms	Assigned Interventions
A: Experimental LX201 0.50" plus topical therapy	Drug: LX201 LX201 is a sustained release silicone implant containing 30% cyclosporine A by weight. The LX201 implant releases the cyclosporine at steady doses over the course of a year. Cyclosporine has also been used in oral form for over 20 years to help prevent the rejection of transplanted organs by the body. LX201 implant is placed in the transparent membrane covering the white of the eye under the eyelid via a simple procedure. LX201 is available in two different lengths, 0.50 and 0.75 inch. Each implant device is 0.08 inch wide and 0.04 inch in height. The implants are flat on the bottom, the top and ends are rounded.
B: Experimental LX201 0.75" plus topical therapy	Drug: LX201 LX201 is a sustained release silicone implant containing 30% cyclosporine A by weight. The LX201 implant releases the cyclosporine at steady doses over the course of a year. Cyclosporine has also been used in oral form for over 20 years to help prevent the rejection of transplanted organs by the body. LX201 implant is placed in the transparent membrane covering the white of the eye under the eyelid via a simple procedure. LX201 is available in two different lengths, 0.50 and 0.75 inch. Each implant device is 0.08 inch wide and 0.04 inch in height. The implants are flat on the bottom, the top and ends are rounded.
C: Placebo Comparator 0.75" placebo implant plus topical therapy	Other: 0.75" Placebo Implant The placebo is a silicone implant 0.75" in length. It contains no cyclosporine

Detailed Description:

Did you know that …

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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00447642

Show 30 Study Locations

Sponsors and Collaborators

Lux Biosciences, Inc.

More Information

Study ID Numbers:	LX201-02
Study First Received:	March 13, 2007
Last Updated:	July 8, 2008
ClinicalTrials.gov Identifier:	NCT00447642
Health Authority:	United States: Food and Drug Administration

Keywords provided by Lux Biosciences, Inc.:

immunology
cornea
allograft
corneal allograft rejection
graft failure

Study placed in the following topic categories:

Corneal Diseases
Cyclosporine
Cyclosporins

ClinicalTrials.gov processed this record on January 16, 2009