A PHASE II PROSPECTIVE, RANDOMIZED, MULTI-CENTER, DIABETIC MACULAR EDEMA DOSE RANGING, COMPARATOR STUDY EVALUATING THE EFFICACY AND SAFETY OF PF-04523655 VERSUS LASER THERAPY (DEGAS)

• Conditions: Diabetic Macular Edema; MedDRA version: 9.1Level: LLTClassification code 10057934Term: Diabetic macular edema

• Registration Number: EUCTR2008-000349-68-GB
• Lead Sponsor: Pfizer Inc. 235 East 42nd Street, New York NY10017

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-06-17
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

1. History of diabetes mellitus (Type 1 or Type 2).
2. Serum HbA1c =5.5% and =12% at the screening visit.
3. Subjects with diffuse diabetic macular edema consisting of retinal thickness on OCT measuring 275 µm or more in the central subfield at the screening visit.
4. Reduced visual acuity resulting from retinal thickening involving the center of the fovea and a best corrected visual acuity, using Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity protocol of 20/40 or worse (letter score of =73) and up to 20/320 or better (letter score =24) in the study eye at the screening visit.
5. Visual acuity score in the fellow eye of 20/400 or better (letter score of =19) at the screening visit.
Note: Only one eye will be treated (study eye), in the event both eyes are eligible for study entry the study eye should be selected by the investigator and subject.
6. Treatment for diabetic macular edema with laser photocoagulation can be withheld for at least 90 days after the subject has enrolled in the study.
7. Ocular media and adequate pupillary dilation to allow good quality OCT and stereoscopic fundus photography.
8. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
9. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures such as telephone access from Call Center for the administration of NEI-VFQ-25
10. Males and females aged 18 years or older. Female subjects either of non-childbearing potential (hysterectomized or believed to be post-menopausal as evidenced by a 3 year history of amenorrhea) or of childbearing potential are eligible, provided they have a negative urine pregnancy test at the Screening and Baseline visit. Female subjects of childbearing potential should be willing to use adequate (at least two forms of) contraceptive methods as described below during the treatment period and for 3 months after the last dose of study medication. Male subjects with partners of childbearing potential must agree to use adequate (at least one form of) contraception as described below during the treatment period and for 3 months after the last dose of study medication or be surgically sterile.
Acceptable contraceptive methods for male (need at least one):
a. Abstinence;
b. Use of condom for males with a vasectomy;
c. Without a vasectomy, must use a condom and be instructed that their female
partner should use another form of contraception such as an IUD, spermicidal
foam/gel/film/cream/suppository, diaphragm with spermicide, oral contraceptive,
injectable progesterone, subdermal implant or tubal ligation if the female partner
could become pregnant from the time of the first dose of trial medication until
3 months after the last dose.
Acceptable contraceptive methods for female (need at least two):
a.Hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing IUDs) at least 14 days prior to the first dose of trial medication;
b.Abstinence;
c.Placement of a copper-containing intrauterine device (IUD);
d.Condom with spermicidal foam/gel/film/cream/suppository;
e.Tubal ligation;
f.Male partner who has had a vasectomy for at least 4 months
Are the trial subjects under 18? no
Number of subjects for this age

Exclusion Criteria

1.Panretinal photocoagulation or macular photocoagulation performed in the study eye within 3 months of the screening visit.
2.Subjects receiving concomitant intravitreal anti-VEGF therapy in the non study eye. Intravitreal steroids in the non study eye are permitted.
3.Any concurrent intraocular condition in the study eye or previous surgery (eg, cataract, vitrectomy) that, in the opinion of the investigator, could either (a) require medical or surgical intervention during the 36-month study period to prevent or treat visual loss that might result from that condition, or (b) if allowed to progress untreated, could likely contribute to loss of at least 2 ETDRS lines of best corrected visual acuity over a 36-month period (c) may affect macular edema or reduce visual acuity during the course of the study eg, uveitis/ ocular inflammatory disease, vein occlusions, Irvine-Gass syndrome.
4.Cataract surgery in the study eye within 2 months prior to study enrollment.
5.High risk proliferative diabetic retinopathy (PDR) in the study eye. Inactive fibrosed neovascularization following pan retinal photocoagulation (PRP) laser therapy and non high risk PDR with no evidence of vitreous hemorrhage is permitted.
6.Current infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
7.Aphakia or absence of the posterior capsule in the study eye. Previous Yttrium Aluminum Garnet (YAG) capsulotomy performed 2 months or more prior to study entry associated with posterior intraocular lens implant is permitted.
8.Structural damage to the center of the macula in the study eye likely to preclude improvement in visual acuity following the resolution of macular edema, including but not limited to persistent DME involving the foveal center of more than 2 years in duration, atrophy of the retinal pigment epithelium, subretinal fibrosis, macular ischemia as defined by an enlarged foveal avascular zone (FAZ >1000µm on fundus fluorescein angiography), laser scar(s), organized hard exudative plaque, vitreomacular traction, epiretinal membrane evident on ophthalmic examination or by OCT.
9.Uncontrolled glaucoma (defined as intraocular pressure treatment with anti-glaucoma medications) with IOP ?30 mm Hg and/or advance disc cupping with glaucomatous visual field loss.
10.Subjects who have a history of any severe acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with study participation or could interfere with the interpretation of study results and, in the judgment of the investigator, could make the subject inappropriate for entry into this study; eg,;
•History of gastrointestinal bleeding within 2 months of study enrollment;
•Renal function insufficiency: serum creatinine >2.5 mg/dL or status post renal transplant or receiving dialysis;
•liver function insufficiency: serum bilirubin >1.5 mg/dL, ALT >2 x ULN, AST > 2 x ULN, alkaline phosphatase > 2 x ULN;
•History or evidence of severe cardiac disease (NYHA Functional Class III or IV) (Appendix 6), medical history of cerebral vascular accident, unstable angina, acute coronary syndrome, transient ischemic attacks, myocardial infarction, revascularization procedure within 6 months prior to screening visit, or ventricular tachyarrythmias requiring ongoing treatment;
•History or evidence of clinically significant peripheral vascular disease such as intermittent claudication or prior amputation;
•Stroke within 12 mo

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate efficacy of three dose levels of PF-04523655 versus laser in improving visual acuity in subjects with diabetic macular edema .<br><br><br>;Primary end point(s): Mean change from baseline (Day 0) at Month 24 in the best corrected visual acuity<br>(BCVA) score, as measured by ETDRS visual acuity protocol.;Secondary Objective: To evaluate the safety and tolerability of PF-04523655 in subjects with diabetic<br>macular edema.<br>• To evaluate the dosing schedule in maintaining the effect of PF-04523655 in subjects with diabetic macular edema.<br>• To evaluate changes in lesion morphology following administration of PF-04523655<br>by fundus photography, fluorescein angiography (FA) and optical coherence<br>tomography (OCT).<br>• To evaluate the efficacy of PF-4523655 on vision related function and well being<br>assessed using the National Eye Institute Visual Function Questionnaire-25 (NEIVFQ-<br>25)<br>• To evaluate systemic exposure of PF-04523655 at 1 week following first dose.