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

Sponsor

Lux Biosciences, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT00447642

Collaborator

(none)

122

Enrollment

Locations

Arms

33.1

Duration (Months)

4.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Corneal Transplantation Corneal Graft Rejection	Drug: LX201 Other: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

122 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

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 Start Date :

Apr 1, 2007

Actual Primary Completion Date :

Aug 1, 2008

Actual Study Completion Date :

Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LX201 0.50 inch implant LX201 implant contained 30% cyclosporine A by weight and 0.50 inch in length	Drug: LX201 LX201 was 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 is 0.08 inch wide and 0.04 inch in height. The implants are flat on one side (the posterior surface, which is applied to the episclera) and the anterior surface and ends were rounded.
Experimental: LX201 0.75 inch implant LX201 implant contained 30% cyclosporine A by weight and 0.75 inch by length	Drug: LX201 LX201 was 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 is 0.08 inch wide and 0.04 inch in height. The implants are flat on one side (the posterior surface, which is applied to the episclera) and the anterior surface and ends were rounded.
Placebo Comparator: Placebo 0.75 inch implant Silicone implant not containing cyclosporine A, 0.75 inch in length	Other: Placebo The placebo was a silicone implant 0.75 inch in length. It contained no cyclosporine A

Arm

Intervention/Treatment

Experimental: LX201 0.50 inch implant

LX201 implant contained 30% cyclosporine A by weight and 0.50 inch in length

Drug: LX201

LX201 was 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 is 0.08 inch wide and 0.04 inch in height. The implants are flat on one side (the posterior surface, which is applied to the episclera) and the anterior surface and ends were rounded.

Experimental: LX201 0.75 inch implant

LX201 implant contained 30% cyclosporine A by weight and 0.75 inch by length

Drug: LX201

Placebo Comparator: Placebo 0.75 inch implant

Silicone implant not containing cyclosporine A, 0.75 inch in length

Other: Placebo

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

Outcome Measures

Primary Outcome Measures

prevention of corneal allograft rejection or graft failure [52 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Cornea Consultants of Arizona	Phoenix	Arizona	United States	85032
2	Loma Linda University Health Care	Loma Linda	California	United States	92354
3	USC Doheny Eye Institute	Los Angeles	California	United States	90033
4	Bascom Palmer Eye Institute	Miami	Florida	United States	33136
5	Emory Eye Center	Atlanta	Georgia	United States	30322
6	University of Illinois at Chicago	Chicago	Illinois	United States	60612
7	Price Vision Group	Indianapolis	Indiana	United States	46260
8	The Eye Center at Union Memorial Hospital	Baltimore	Maryland	United States	21218
9	Wilmer Eye Institute, Cornea Service	Baltimore	Maryland	United States	21287
10	New England Eye Center	Boston	Massachusetts	United States	02111
11	W.K. Kellogg Eye Center - University of Michigan	Ann Arbor	Michigan	United States	48105
12	MN Eye Consultants, P.A.	Bloomington	Minnesota	United States	55431
13	Tauber Eye Center	Kansas City	Missouri	United States	64111
14	Ophthalmology Associates	St. Louis	Missouri	United States	63141
15	UMDNJ - New Jersey Medical School Institute of Ophthalmology and Visual Science	Newark	New Jersey	United States	07103
16	New York Eye and Ear Infirmary	New York	New York	United States	10003
17	Mount Sinai School of Medicine	New York	New York	United States	10029
18	Ophthalmic Consultants of Long Island	Rockville Center	New York	United States	11570
19	Cornea Consultants of Albany	Slingerlands	New York	United States	12159
20	Duke University Eye Center	Durham	North Carolina	United States	27705
21	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
22	Cornea Associates of Texas	Dallas	Texas	United States	75231
23	Virginia Eye Consultants	Norfolk	Virginia	United States	23502
24	Eye Associates NW	Seattle	Washington	United States	98104
25	Augenklinik, Universitat Erlangen-Nurnberg	Erlangen		Germany	91054
26	Cornea Bank, Universitätsklinikum Essen	Essen		Germany	45122
27	Klinik fuer Ophthalmologie Campus Kiel	Kiel		Germany	24105
28	Ludwig Maximilians Universität	Muenchen		Germany	80336
29	Augenklinik der Technischen Universität München	München		Germany	81675
30	Augenklinik Wuerzburg	Wuerzburg		Germany	97080