E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Macula oedema secondary to branch retinal vein occlusion |
|
E.1.1.1 | Medical condition in easily understood language |
Blockage of veins in the eye that leads to build up of fluid causing swelling in the area of the retina called the macula. This may lead to
damage to the macula which affects your central vision. |
|
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 | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025415 |
E.1.2 | Term | Macular oedema |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038907 |
E.1.2 | Term | Retinal vein occlusion |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
|
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 compare the efficacy and safety of Ozurdex vs. Lucentis in subjects
with BRVO |
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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 |
1. Male or female, ≥ 18 years of age
2. Written informed consent has been obtained
3. No inclusion criterion associated with this number
4. Study eye must have clear ocular media and adequate pupil dilation to permit good quality photographic imaging
5. ME secondary to BRVO in the study eye with all of the following characteristics:
a) involving the centre of the macula (fovea)
b) central retina subfield thickness ≥ 320 μm as assessed with Spectralis optical coherence tomography (OCT) or ≥ 300 μm as assessed with Cirrus OCT
c) less than 90 days from onset of BRVO symptoms to screening visit
d) visual acuity (VA) decrease attributable to retinal oedema
Note: Characteristics a and b will be confirmed by a CRC
6. Absence of severe macular ischemia (defined as an area of nonperfusion > 4 disc areas [DA] which involve the foveal avascular zone), as confirmed by a CRC
7. BCVA score of ≥ 20 to ≤ 70 letters (20/40 to 20/400 Snellen equivalent) using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol at both the screening visit and day 1 visit.
8. Female subjects of childbearing potential must have a negative urine pregnancy test at the screening (day -14) visit. |
|
E.4 | Principal exclusion criteria |
1. History of a medical condition (disease, metabolic dysfunction, physical examination finding or clinical laboratory finding) that, in the opinion of the investigator, would preclude scheduled study visits, completion of the study, or a safe administration of study medication.
2. Ocular hypertension unless controlled with monotherapy.
3. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine (human chorionic gonadotropin [hCG] > 20 mIU/ml) or serum pregnancy test (hCG ≥ 5 mIU/ml).
4. Pre-menopausal women of child-bearing potential not using adequate contraception. Women of child-bearing potential are defined as all women physiologically capable of becoming pregnant. This includes women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means unless they meet the following definition of postmenopausal:12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels of > 40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy. Adequate
contraception is defined as one or more of the following methods: surgical sterilization (eg, bilateral tubal ligation), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of intrauterine device, male or female condom with spermicidal gel, diaphragm, sponge, or cervical cap). Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the subject ensures compliance. Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and
withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after the administration of the last study drug injection.
Note: Instruct females of childbearing potential to immediately inform the investigator if they become pregnant during the study. Should this occur, the investigator shall immediately contact the Sponsor as detailed in Sections 9.2 and 9.3 of the protocol.
5. Participation in an investigational drug or device study within 30 days of the screening visit
6. Any current or history of ocular disease in the study eye other than RVO that, in the opinion the investigator, may confound assessment of the macula or affect central vision, such as exudative age-related macular degeneration, geographic atrophy, diabetic retinopathy, uveitis, angioid streaks, histoplasmosis, pathological myopia, retinal detachment, epiretinal membrane, macular hole, or significant cataract
7. History of cataract surgery in either eye within the past 3 months prior to the screening visit
8. History or evidence of serious ocular trauma or intraocular surgery (such as laser-assisted in situ keratomileusis, keratoplasty, vitrectomy) in the study eye within the past 6 months prior to the screening visit
9. History of severe or serious hypersensitivity to any components of the test article or fluorescein dye.
10. > 10-Letter improvement in BCVA between the screening visit and day 1
11. Brisk afferent pupillary defect (ie, obvious and unequivocal)
12. Aphakic study eye with rupture of the posterior lens capsule or, pseudophakic study eye with Anterior Chamber Intraocular Lens (ACIOL) and rupture of the posterior lens capsule.
13. Any active ocular infection (ie, bacterial, viral, parasitic, or fungal) in adnexa of either eye
14. History of radial optic neurotomy or sheathotomy
15. Laser photocoagulation for ME in the study eye within 3 months prior to the screening visit
16. Anticipated need for ocular surgery or ophthalmic laser treatment in the study eye during the 12-month study period
17. Prior anti-VEGF treatment in study or fellow eye within 3 months of screening or systemic anti-VEGF treatment within 6 months of the screening visit
18. Use of intraocular, intravitreal, or peri-ocular steroids in the study eye within 3 months of the screening visit
19. Use of systemic steroids (eg, oral, intravenous, intra-articular, epidural, intrabursal) within 1 month of screening or anticipated use at any time during the study. Inhaled and intranasal steroids are allowed.
20. IOP > 22 mm Hg at screening or day 1 visit in either eye. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is mean change in BCVA at month 12. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
BCVA assessment at screening, baseline, day 7 and at each monthly visit. |
|
E.5.2 | Secondary end point(s) |
1. Mean change in the central retina subfield thickness between baseline and month 6, and between baseline and month 12
2. Proportion of subjects with ≥ 15-letter improvement in BCVA between baseline and month 12
3. Proportion of subjects with ≥ 15-letter decrease in BCVA between baseline and month 12
4. Change from baseline in vision-dependent subfields of the VFQ-25 questionnaire including near vision, far vision, and vision-dependent activity at month 3, month 6, and month 12.
5. Proportion of subjects in each treatment arm not completing the month 12 visit due to treatment failure (as defined in the protocol). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. OCT assessments that will be used in evaluation of timepoint will be done at baseline, month 6 and month 12.
2. and 3. BCVA assessments that will be used in evaluation of timepoints will be done at baseline and month 12.
4. VFQ-25 questionnaire completed at baseline, month 3, month 6, and month 12. |
|
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 | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 39 |
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 |
France |
Germany |
Israel |
Italy |
Spain |
United Kingdom |
|
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
|
|
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 | 1 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |