| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subfoveal Choroidal Neovascularization (CNV) associated with 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 | 10060837 |
| E.1.2 | Term | Choroidal neovascularization |
|
| 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 |
Stage I
• To evaluate the onset of action of PF-04523655 for further study in Stage II as either first line (initial) therapy or following induction therapy (following a single intravitreal injection of ranibizumab 0.5 mg) in subjects with neovascular AMD.
Stage II
• To evaluate the dose response of PF-04523655 when given either as first line (initial) therapy or following induction therapy (following a single intravitreal injection of ranibizumab 0.5 mg) as determined from Stage I versus ranibizumab (comparator) in subjects with neovascular AMD. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of PF-04523655 in subjects with CNV associated with AMD
To evaluate changes in retinal central subfield thickness and retinal lesion thickness by Optical Coherence Tomography
To evaluate changes in lesion morphology following intravitreal administration of PF-04523655 by fluorescein angiography
To evaluate the efficacy and durability of PF-04523655 for the preservation of visual function related quality of life as measured by the 25-item version of the National Eye Institute Visual Functioning Questionnaire in subjects with CNV associated with AMD at study sites where such evaluation is feasible
The following objectives will be explored at centers where available:
To evaluate autofluorescence as a predictor and measure of response following intravitreal administration of PF-04523655
To evaluate OCT changes using spectral domain OCT in the retina and choroid following intravitreal administration of PF-04523655 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Males and females age 50 years or older with active primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to agerelated macular degeneration (AMD). Active CNV is defined as any leakage detected on FFA or OCT. The following subjects will be eligible for study enrollment:
a. Subjects who are treatment naïve to neovascular AMD (CNV) therapy;
b. Subjects previously/ currently receiving chronic CNV therapy (<7 previous injections) who have previously shown a positive response to their therapy in the study eye (anatomically dry retina on previous OCT scan or a 5 letter improvement in VA). These subjects will be eligible to participate in the study if continued treatment is necessitated for their CNV due to reaccumulation of sub retinal fluid eg, Reaccumulation of retinal fluid of at least 50 µm in the central subfield thickness at least 1 month after last treatment will be considered eligible. Note: Female subjects 50- 60 years of age must be amenorrheic for at least 2 years and have a serum FSH level within the laboratory reference range for postmenopausal women.
2. The total area of CNV (including both classic and occult components) encompassed within the lesion must be 50% or more of the total lesion area.
3. The total lesion size ≤12 disc areas.
4. Best corrected visual acuity using ETDRS protocol of 20/40 to 20/320 (letter score ≤73) in the study eye at the screening visit.
5. Best corrected 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) through the duration of the study. In the event both eyes are eligible for study entry the study eye should be selected by the investigator and subject. The non-study eye may be treated with an approved AMD therapy.
6. Subject has retinal central subfield thickness ≥250µm measured using Stratus OCT.
7. 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.
8. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
|
| E.4 | Principal exclusion criteria |
1. Prior treatment with verteporfin photodynamic therapy, external-beam radiation therapy, or transpupillary thermotherapy in the study eye.
2. Previous subfoveal focal laser photocoagulation in the study eye.
3. Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1 month preceding Baseline.
4. Previous non response to ranibizumab therapy (See inclusion criterion 1b) in the study eye.
5. History of vitrectomy, submacular surgery or other surgical intervention for AMD in the study eye.
6. Previous participation in any studies with investigational drugs or treatments administered 1 month preceding Baseline visit such as systemic glucocorticoids, ocular or periocular steroids (eg, triamcinolone, anecortave acetate), antiangiogenic drugs such as pegaptanib (Macugen), ranibizumab (Lucentis), bevacizumab (Avastin)
in the study eye.
7. Subretinal hemorrhage in the study eye that involves the fovea, if the size of the hemorrhage is either 50% or more of the total lesion area or 1 or more disc areas in size.
8. CNV in either eye of other etiology, eg, ocular histoplasmosis, trauma, or pathologic myopia.
9. Presence of subfoveal scarring.
10. Retinal pigment epithelial tear involving the macula in the study eye.
11. Any concurrent ocular condition in the study eye (eg, cataract or diabetic retinopathy) that, in the opinion of the investigator, could either
(a) require medical or surgical intervention during the 12-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 5 letters (ETDRS) of best corrected visual acuity over the 12-month study period.
12. Current active intraocular inflammation (grade “trace” or above) or history of idiopathic /autoimmune uveitis in either eye.
13. Vitreous hemorrhage present in the study eye.
14. History of rhegmatogenous retinal detachment or macular hole (any Stage) in the study eye.
15. Current infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
16. Aphakia or absence of the posterior capsule in the study eye. YAG capulotomy in association with posterior intraocular lens implant is permitted.
17. Spherical equivalent of the refractive error in the study eye demonstrating more than −8 diopters of myopia.
18. Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Baseline.
19. Uncontrolled glaucoma in the study eye (defined as intraocular pressure of 30 mmHg or more despite treatment with antiglaucoma medications).
20. History of glaucoma filtering surgery in the study eye.
21. History of corneal transplant in the study eye.
22. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications.
23. Current treatment for active systemic infection.
24. Inability to obtain fundus photographs, FFA or OCT of sufficient quality to be analyzed and graded by the central reading center.
25. Inability to comply with study or follow-up procedures.
26. History of gastrointestinal bleeding 2 months prior to study enrollment.
27. History of procedure/surgery with increased risk of thromboembolism such as but not limited to major gastrointestinal, cardiothoracic, gynecological, genitourinary, or orthopedic surgeries 2 months prior to study enrollment.
28. History of cerebral vascular accident, myocardial infarction, transient ischemic attacks 6 months prior to study enrollment. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Stage I
• Proportion of subjects in each dose cohort of PF-04523655 (0.4 mg, 1 mg, 3 mg) responding to treatment at 2 weeks.
A responder is defined as a subject whose retinal central subfield thickness (measured using OCT) has at least a 50 µm reduction or whose Best Corrected Visual Acuity (BCVA) score (measured using ETDRS protocol) improves by at least 5 letters at the Week 2 visit.
Stage II
• Mean change in the best corrected visual acuity score measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at Week 48. |
|
| 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 | Yes |
| 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) | 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 | 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.8.3 |
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 | 72 |
| 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
| |
| 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 | 11 |
| E.8.9.1 | In the Member State concerned days | 6 |
| 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 | 11 |
| E.8.9.2 | In all countries concerned by the trial days | 6 |
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