E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic Macular Edema (DME) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
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 |
The objective of this trial will be to confirm the safety and compare the efficacy of pegaptanib sodium when subjects are given intravitreous injections of 0.3 mg/eye versus sham injections in a 1:1 ratio, respectively. All subjects previously randomized to the 0.03 or 0.003 mg/eye treatment arms during the conduct of EOP1013 through EOP1013C will be given the option of either receiving injections of 0.3 mg/eye or withdrawing from the study. Injections will be given as often as every 6 weeks for 2 years, in subjects with diabetic macular edema (DME) involving the center of the macula associated with vision loss not due to ischemia. There will be an optional, open-label, year long extension phase which will provide all who participate the opportunity to receive Macugen therapy. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
OPHTHALMIC CRITERIA 1. Subjects must have macular edema that involves the center of the macula with corresponding leakage on fluorescein angiogram. Leakage will be confirmed retrospectively by the IRC. 2. Foveal thickness of at least 250 microns (OCT center point thickness), with a standard deviation of the center point of <10%, an OCT signal strength of ≥5 is recommended, and properly created ILM and RPE borders at Baseline by computer software. In cases that the OCT image software fails to properly draw ILM and RPE borders, if the IRC obtains a manual estimate of OCT center point thickness of at least 250 microns, then the patient will be considered eligible. 3. Best corrected distance visual acuity in the study eye must be a letter score between 65 and 35 inclusive (20/50 to 20/200 Snellen equivalents). 4. Clear ocular media and adequate pupillary dilatation to permit good quality stereoscopic fundus photography. 5. Intraocular pressure of 21 mmHg, or less. 6. The treating ophthalmologist should be comfortable that focal laser (direct and grid as needed) can be deferred for at least 18 weeks in the study eye, even though focal or grid laser is indicated.
GENERAL CRITERIA 1. Type I, or Type II diabetic subjects as defined by the WHO criteria of either gender, and aged ≥ 18 years . 2. Performance Status ≤ 2 according to the Eastern Cooperative Oncology Group (ECOG) / World Health Organization (WHO) scale. (See Appendix 15.6) 3. Normal electrocardiogram (ECG), or clinically non-significant changes. 4. Women must be using effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile. All women of childbearing potential must have a negative serum pregnancy test at baseline and negative urine pregnancy tests immediately prior to each injection and use two effective forms of contraception during the trial and for at least 60 days following the last dose of pegaptanib sodium. 5. Adequate hematological function: hemoglobin ≥10 g/dL; platelet count ≥130 x 109/l; WBC ≥ 3.8 x 109/l. 6. Adequate liver function: serum bilirubin ≤1.5 mg/dL; SGOT/ALT, SGPT/AST, GGT and alkaline phosphatase within 2 x ULN. 7. Adequate renal function: serum creatinine ≤ 2.5 mg/dL and BUN within 2.5 x ULN. 8. Ability to provide written informed consent. 9. Ability to return for all trial visits.
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E.4 | Principal exclusion criteria |
Subjects will not be eligible for the trial if any of the following criteria are present systemically, or in the study eye: 1. Eyes with prior scatter (panretinal) photocoagulation less than 6 months prior to baseline angiography/photography or eyes in which scatter (panretinal) photocoagulation is needed now or is likely to be needed within the next 9 months (e.g. eyes with DRS high risk PDR not already adequately treated with photocoagulation). 2. Presence of any abnormality that is likely to confound assessment of visual acuity improvement in eyes in which macular edema resolves, or improves, such as non-perfusion for >1 disc area involving the foveal avascular zone (FAZ - involving 2 or more quadrants centered around the foveal avascular zone), epiretinal membrane associated with signs of contraction and/or significant opacification (i.e. striae within 1 disc diameter of the foveal center), or presence of chorioretinal atrophy involving the center of the macula. 3. Vitreomacular traction determined clinically and/or by OCT, which, in the investigator’s opinion, contributes to the macular edema (or causes associated foveal detachment), and would preclude improvement with pegaptanib sodium or sham treatment. 4. Any other cause of macular edema such as vitreous extension, or entrapment to anterior segment wound, or any retinal vein occlusion involving the macula. 5. Atrophy/scarring/fibrosis involving the center of the macula, including evidence of laser treated atrophy within 200 microns of FAZ. 6. Any subfoveal hard exudates, or RPE atrophy (by fundus examination, fundus photograph, FA or OCT). 7. Subjects who have received YAG laser, or peripheral retinal cryoablation, or laser retinopexy (for retinal tears only), or focal or grid photocoagulation, within the previous 16 weeks. 8. Significant media opacities, including cataract, which might interfere with visual acuity, assessment of toxicity or fundus photography. Subjects should not be entered if there is likelihood that they will require cataract surgery within the following 1 year. 9. Any intraocular surgery within 6 months of trial entry. 10. Previous vitrectomy. 11. HbA1C level >10% or recent signs of uncontrolled diabetes (3 or more episodes of severe hypoglycemia by DCCT (Diabetes Control and Complications Trial) definition [10] within 3 months of baseline, or 2 or more episodes of ketoacidosis within 1 year of baseline, or an episode of ketoacidosis within 3 months of baseline). 12. Any of the following underlying systemic diseases including: •History or evidence of severe cardiac disease, e.g. NYHA Functional Class III or IV (Appendix 15.7), clinical or medical history of unstable angina, acute coronary syndrome, myocardial infarction, or revascularization procedure within 6 months prior to baseline, or ventricular tachyarrythmias requiring ongoing treatment. •History or evidence of clinically significant peripheral vascular disease such as intermittent claudication or prior amputation. •Clinically significant impaired renal function (serum creatinine >2.5 mg/dL or s/p renal transplant or receiving dialysis). •Clinically significant impaired hepatic function. •Stroke (within 12 months of trial entry). •Any major surgical procedure within one month of trial entry. 13. Previous radiation to the head in the region of the study eye. 14. Any of the following prior treatments or at anytime during the study: •Investigational agents for DME (including intravitreal, subconjunctival or subtenons corticosteroids) at any time in the study eye. Treatment with Avastin in either the study eye or fellow eye is not allowed at anytime. •Avastin or any investigational agent during the past 90 days for any other nonocular condition. 15. Known serious allergies to the fluorescein dye used in angiography, or to the components of pegaptanib sodium formulation. 16. Systolic BP > 160 (2 different readings) or diastolic BP > 100 (2 different readings). 17. Acute ocular or periocular infection. 18. Previous filtering surgery (e.g., trabeculectomy) or placement of a glaucoma drainage devise (e.g., tube-shunt surgery). 19. Pathological high myopia (spherical equivalent of negative 8 diopters or more, or axial length of 25 mm or more). 20. Women who are currently nursing
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary: The proportion of subjects exhibiting an improvement ≥ 10 letter (or 2-line) of vision (ETDRS) from baseline. The 1 year endpoint is the primary endpoint, while the 2 year endpoint will be the secondary endpoint. Secondary (at 1 and 2 years unless specified): *The proportion of subjects with a ≥15 letter improvement at 1 and 2 years. * The proportion of eyes experiencing a change in the degree of retinopathy by 2 or more steps. * Changes in mean visual acuity over time. * The proportion of subjects requiring focal or grid laser.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.4 | Double blind | Yes |
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) | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
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 | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |