E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neovascular age-related macular degeneration (AMD) |
|
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 | 10064930 |
E.1.2 | Term | Age-related macular degeneration |
|
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 assess the efficacy of intravitreally (ITV) administered VEGF Trap-Eye compared to ranibizumab (in a non-inferiority paradigm) in preventing moderate vision loss in subjects with all subtypes of neovascular AMD. |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of repeated ITV administration of VEGF Trap-Eye in subjects with all subtypes of neovascular AMD for up to 2 years. To assess the effect of repeated ITV administration of VEGF Trap-Eye in vision-related quality of life (QOL) in subjects with all subtypes of neovascular AMD, as assessed using the NEI VFQ-25. To describe systemic exposure to the study drug.
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacogenomic investigations in AMD patients participating in the clinical study VIEW2. Evaluation of potential naso-mucosal side effects in a subset of subjects participating in the clinical study VIEW 2 from selected centers, also in the Netherlands. |
|
E.3 | Principal inclusion criteria |
1. Signed Informed Consent. 2. Men and women ≥ 50 years of age. 3. Active primary subfoveal CNV lesions secondary to AMD, including juxtafoveal lesions that affect the fovea as evidenced by FA in the study eye. 4. ETDRS best-corrected visual acuity of: 20/40 to 20/320 (letter score of 73 to 25) in the study eye. 5. Willing, committed, and able to return for ALL clinic visits and complete all study-related procedures. 6. Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member. Able to understand and willing to sign the informed consent form. 7. The area of CNV must occupy at least 50% of total lesion.
|
|
E.4 | Principal exclusion criteria |
1. Any prior ocular (in the study eye) or systemic treatment or surgery for neovascular AMD, except dietary supplements or vitamins. 2. Any prior or concomitant therapy with another investigational agent to treat neovascular AMD in the study eye. 3. Any prior treatment with anti-VEGF agents in the study eye. 4. Total lesion size >12 disc areas (30.5 mm2, including blood, scars and neovascularization) as assessed by FA in the study eye. 5. Subretinal hemorrhages that is either 50% or more of the total lesion area, or if the blood is under the fovea and is 1 or more disc areas in size in the study eye. (If the blood is under the fovea, then the foevea must be surrounded by 270 degrees by visible CNV). 6. Scar or fibrosis making up >50% of the total lesion in the study eye. 7. Scar, fibrosis, or atrophy involving the center of the fovea in the study eye. 8. Presence of retinal pigment, epithelial tears or rips involving the macula in the study eye. 9. History of any vitreous hemorrhage within 4 weeks prior to Visit 1 in the study eye. 10. Presence of other causes of CNV in the study eye. 11. Prior vitrectomy in the study eye. 12. History of retinal detachment or treatment or surgery for retinal detachment in the study eye. 13. Any history of macular hole of stage 2 and above in the study eye. 14. Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of Day 1, as long as it is unlikely to interfere with the injection. 15. Prior trabeculectomy or other filtration surgery in the study eye. 16. Uncontrolled glaucoma (defined as intraocular pressure >=25 mmHg despite treatment with antiglaucoma medication) in the study eye. 17. Aphakia or psuedophakia with absence of posterior capsule (unless it occurred as a result of a yttrium aluminum garnet [YAG] posterior capsulotomy) in the study eye. 18. Previous therapeutic radiation in the region of the study eye. 19. History of corneal transplant or corneal dystrophy in the study eye. 20. Significant media opacities, including cataract, in the study eye which might interfere with visual acuity, assessment of toxicity or fundus photography. 21. History or clinical evidence of diabetic retinopathy, diabetic macular edema or any retinal vascular disease other than AMD in either eye. 22. Active intraocular, extraocular and periocular inflammation or infection in either eye. 23. Any ocular or periocular infection within the last 2 weeks prior to screening in either eye. 24. Any history of uveitis in either eye. 25. Presence of Scleromalacia in either eye. 26. Any concurrent intraocular condition in the study eye that could require either medical or surgical intervention during the 96-week study period. 27. Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the subject safety or which otherwise may interfere with evaluation of efficacy or safety. 28. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug. 29. Participation as a subject in any clinical study within 12 weeks prior to Day 1. 30. Any systemic or ocular treatment with an investigational agent in the past 3 months prior to Day 1. 31. The use of long acting steroids, either systemically or intraocularly, in the 6 months prior to Day 1. 32. Any history of allergy to povidone iodine. 33. Known serious allergy to the fluorescein sodium for injection in angiography. 34. Presence of any contraindications indicated in the EMEA approved label for ranibizumab. Further details are provided in the attached label in Section 14.2. Contraindications include the following: •Known allergic reactions and/or hypersensitivity to ranibizumab or to any ingredients of the study medication. • Presence of any infection in or around the eye. • Presence of pain or redness (severe intraocular inflammation) in the eye. 35. Females who are pregnant, breastfeeding, or of childbearing potential, unwilling to practice adequate contraception throughout the study. Adequate contraceptive measures include oral contraceptives (stable use for 2 or more cycles prior to screening), intrauterine devices, hormonal injections, hormonal implants, bilateral tubal ligation, vasectomy, condom or diaphragm plus either contraceptive sponge, foam or jelly.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects who maintain vision at Week 52, where a subject is classified as maintaining vision if the subject has lost fewer than 15 letters in the ETDRS letter score compared to baseline (ie, prevention of moderate vision loss). |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
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) | 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 | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 130 |
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 |
|
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
|
The end of study visit (visit 27) will occur approximately 4 weeks after the end of study medication. End-of-Study visit is performed at week 96 for subjects who received their last injection at least 8 weeks prior to this visit. Subjects who have received an injection at Visit 26 will have this visit at Week 100, i.e. 8 weeks after their last injection. In addition, they will have an extra visit 4 weeks after their last injection even though no injection is given at this visit. |
|
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 | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |