E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057934 |
E.1.2 | Term | Diabetic macular edema |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate efficacy of three dose levels of PF-04523655 versus laser in improving visual acuity in subjects with diabetic macular edema.
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of PF-04523655 in subjects with diabetic macular edema. • To evaluate the dosing schedule in maintaining the effect of PF-04523655 in subjects with diabetic macular edema. • To evaluate changes in lesion morphology following administration of PF-04523655 by fundus photography, fluorescein angiography (FA) and optical coherence tomography (OCT). • To evaluate the efficacy of PF-4523655 on vision related function and well being assessed using the National Eye Institute Visual Function Questionnaire-25 (NEIVFQ- 25) • To evaluate systemic exposure of PF-04523655 at 1 week following first dose. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 diabetic macular edema affecting the fovea 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. Note: Because the questionnaire or certified interviewers may not be available in all local languages needed, certain countries or sites or individuals will be exempt from this requirement (with prior approval from the sponsor). Those countries/sites/individuals impacted will be identified in a note to file. 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 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. 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. |
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E.4 | Principal 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 months of baseline visit; •History of procedure/surgery with increased risk of thromboembolism such as but not limited to major gastrointestinal, cardiothoracic, gynecological, genitourinary, or orthopedic surgeries within 2 months of study enrollment; •Poor glycemic control expected to require initiation of insulin treatment within the next 4 months from baseline should not be enrolled into the study. 11.Subjects with blood pressure >180/110 at screening visit should be excluded. Subjects with blood pressure equal or below 180/110 with anti-hypertensive medication may be enrolled into the study. 12.Subjects who show a clinically significantly abnormal ECG, suggesting ischemic heart diseases, clinically significant cardiac arrhythmias, atrioventricular block, congestive heart failure as determined by a physician at screening. In case a clinically significant abnormality is shown at screening, the ECG should be assessed at baseline again to determine the eligibility.
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from baseline (Day 0) at Month 24 in the best corrected visual acuity (BCVA) score, as measured by ETDRS visual acuity protocol. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 36 |
E.8.9.2 | In all countries concerned by the trial days | 0 |