E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057934 |
E.1.2 | Term | Diabetic macular edema |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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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 whether treatment with 700 μg DEX PS DDS every 5 months provides a similar treatment effect on average change of best-corrected visual acuity (BCVA) as ranibizumab administered as per its European Summary of Product Characteristics (SmPC) in patients with DME |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the effects of 700 μg DEX PS DDS on central retinal thickness (CRT) and other anatomical changes relative to ranibizumab 0.5 mg in patients with DME.
• To evaluate the effects of 700 μg DEX PS DDS on patient-reported outcomes (PROs) relative to ranibizumab 0.5 mg in patients with DME.
• To evaluate the safety of 700 μg DEX PS DDS relative to ranibizumab 0.5 mg in patients with DME.
• To evaluate the effect of 700 μg DEX PS DDS on BCVA average change in
pseudophakic subgroup of patients relative to ranibizumab 0.5 mg in patients with DME |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, at least 18 years of age.
2. Diagnosis of diabetes mellitus (type 1 or type 2) as defined by the World Health Organization/International Diabetes Federation (Report of a WHO/IDF consultation, 2006)
- Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL) or
- Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) 2 hours after a 75 g oral glucose load as in a glucose tolerance test.
3. Presence of macular edema associated with diabetic retinopathy defined as macular thickening by optical coherence tomography (OCT) assessed by the investigator in the study eye with the following characteristics:
- involving the center of the macula (fovea)
- VA decrease attributable to macular edema
4. BCVA score ≥ 34 and ≤ 70 letters (approximately 20/200 to 20/40 on the Snellen scale) using the Early Treatment Diabetic Retinopathy Study (ETDRS) method in the study eye at the screening visit.
5. Study eye mean retinal thickness by spectral domain OCT in the 1 mm central macular subfield of ≥ 300 μm with Spectralis (Heidelberg) or 275 μm with Cirrus (Zeiss) as determined by the investigator at the screening visit.
6. (Both Eyes) Media clarity, pupillary dilation, and patient cooperation sufficient for all study procedures.
7. Written informed consent has been obtained in accordance with state and country privacy requirements, where applicable. |
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E.4 | Principal exclusion criteria |
Systemic conditions or treatments
1. History of disease, metabolic dysfunction, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of the investigational drug, might affect the interpretation of study results or render the patient at high risk from treatment complications.
2. HbA1c (glycated hemoglobin) >12% at baseline.
3. Untreated diabetes mellitus or initiation of oral anti-diabetic medication or insulin within 4 months prior to baseline or anticipated change of anti-diabetic medications during the 1-year study participation.
4. Renal failure requiring hemodialysis or peritoneal dialysis within 6 months prior to baseline or anticipated need for hemodialysis or peritoneal dialysis at any time during the study or adjusted glomerular filtration rate < 50 mL/min.
5. Use of systemic (eg, oral, intravenous, intramuscular, epidural, rectal, or extensive dermal) corticosteroids within 1 month prior to screening.
6. Uncontrolled systemic disease
Ocular concomitant conditions/disease
7. Any current or history of ocular disease in the study eye, other than DME that in the opinion of the investigator may confound assessment of the macula or affect central vision (for example: exudative age-related macular degeneration [AMD], geographic atrophy, macular edema due to retinal vein occlusion, uveitis, angioid streaks, histoplasmosis, active or inactive cytomegalovirus, pathological myopia, retinal detachment, macular traction, macular fibrosis or scarring, macular hole, significant cataract).
8. Increased intraocular pressure (IOP ≥ 22 mmHg) at screening or day 1, or diagnosis of glaucoma.
9. Any active ocular inflammation or ocular infection (ie, bacterial, viral, parasitic, or fungal) in either eye at the screening visit.
10. Aphakia in the study eye or break in the posterior capsule in the study eye, unless it is a small break resulted from a YAG laser posterior capsulotomy in association with prior posterior intraocular lens implantation
11. Anticipated need for ocular surgery in the study eye during the 1-year study participation.
12. Active proliferative diabetic retinopathy and/or rubeosis.
13. BCVA score < 34 letters in fellow eye.
Ocular treatment
14. Laser photocoagulation to the study eye within 3 months prior to screening.
15. Use of anti-VEGF treatment in study eye within 3 months prior to screening or use of systemic anti-VEGF within 6 months prior to screening
16. Use of intravitreal triamcinolone within 6 months prior to screening.
17. Use of topical intraocular, intravitreal (except triamcinolone, see above) or periocular corticosteroids within 3 months prior to screening in the study eye or ocular conditions in the study eye that require chronic concomitant therapy with topical, local ocular or systemically administered corticosteroids.
18. History of use of DEX PS DDS within 9 months prior to screening.
19. History of cataract surgery within the 3 months prior to baseline.
20. History of vitrectomy.
21. History of incisional glaucoma surgery.
22. Known allergy, hypersensitivity or contraindication to the study medications, its components, fluorescein or povidone iodine.
Compliance / administrative.
23. Female patients who are pregnant, nursing, or planning a pregnancy, or who are of childbearing potential and not using a reliable means of contraception.
24. Current enrollment in an investigational drug or device study or participation in such a study within the 30 days prior to day 1
25. Patient has a condition or is in a situation which, in the investigator’s opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with the patient’s participation in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The average change from baseline in BCVA across all follow-up visits will be calculated for each patient. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At every visit - screening, randomization (Day 1), Month 1-12 visits. |
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E.5.2 | Secondary end point(s) |
(1) Change from baseline in the foveal thickness based on optical coherence tomography (OCT).
(2) Change from baseline in total leakage area based on fluorescein angiography (FA). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
OCT assessment at every visit (screening, randomization (Day1), Month 1-12 visits)
FA assessment at screening, month 6 and month 12. |
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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 | 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) | 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 | Yes |
E.8.1.3 | Single blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 | No |
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 |
Austria |
Belgium |
Brazil |
Denmark |
France |
Germany |
Israel |
Italy |
Netherlands |
Portugal |
South Africa |
Spain |
Sweden |
United Kingdom |
United States |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |