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

Corneal Diseases Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00447187
• Other study ID #: LX201-01
• Status: Terminated
• Phase: Phase 3
• First received: March 12, 2007
• Last updated: October 9, 2012
• Start date: April 2007
• Est. completion date: November 2010

Study information

• Verified date: October 2012
• Source: Lux Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 368
• Est. completion date: November 2010
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cornea Transplant
• Corneal Diseases

Intervention

Drug:
• 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.

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

Locations

Country	Name	City	State
Germany	Augenklinik, Universitat Erlangen-Nurnberg	Erlangen
Germany	Cornea Bank, Universitätsklinikum Essen	Essen
Germany	Klinik fuer Ophthalmologie Campus Kiel	Kiel
Germany	Ludwig Maximilians Universität	Muenchen
Germany	Augenklinik der Technischen Universität München	München
Germany	Augenklinik Wuerzburg	Wuerzburg
United States	W.K. Kellogg Eye Center - University of Michigan	Ann Arbor	Michigan
United States	Emory Eye Center	Atlanta	Georgia
United States	The Eye Center at Union Memorial Hospital	Baltimore	Maryland
United States	Wilmer Eye Institute, Cornea Service	Baltimore	Maryland
United States	MN Eye Consultants, P.A.	Bloomington	Minnesota
United States	New England Eye Center	Boston	Massachusetts
United States	University of Illinois at Chicago	Chicago	Illinois
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Cornea Associates of Texas	Dallas	Texas
United States	Duke University Eye Center	Durham	North Carolina
United States	Price Vision Group	Indianapolis	Indiana
United States	Tauber Eye Center	Kansas City	Missouri
United States	Loma Linda University Health Care	Loma Linda	California
United States	USC Doheny Eye Institute	Los Angeles	California
United States	Bascom Palmer Eye Institute	Miami	Florida
United States	Mount Sinai School of Medicine	New York	New York
United States	New York Eye and Ear Infirmary	New York	New York
United States	UMDNJ - New Jersey Medical School Institute of Ophthalmology and Visual Science	Newark	New Jersey
United States	Virginia Eye Consultants	Norfolk	Virginia
United States	Cornea Consultants of Arizona	Phoenix	Arizona
United States	Ophthalmic Consultants of Long Island	Rockville Center	New York
United States	Eye Associates NW	Seattle	Washington
United States	Cornea Consultants of Albany	Slingerlands	New York
United States	Ophthalmology Associates	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Lux Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	graft rejection or graft failure		52 weeks	No

External Links

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