| 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 |
| To evaluate the efficacy of different dosing paradigms of PF-04523655 versus ranibizumab (comparator) in subjects with neovascular AMD. |
|
| E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of repeat intravitreal injections 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 (OCT);
To evaluate changes in lesion morphology following intravitreal administration of PF-04523655 by fundus fluorescein angiography (FFA); |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
1. Males and females age 50 years or older with active primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and are naïve to any previous treatment for neovascular AMD. Active CNV is defined as any leakage detected on FFA or OCT.
Note: Women of non child bearing potential will be defined as female subjects 50- 60 years of age who are amenorrheic for at least 2 years and have a serum FSH level within the laboratory reference range for postmenopausal women. Female subjects of childbearing potential are eligible for the study but should be willing to use adequate (at least two forms of) contraceptive methods as described below during the treatment period and for 3 months after the last dose of study medication. Male subjects with partners of childbearing potential must agree to use adequate (at least one form of) contraception as described below during the treatment period and for 3 months after the last dose of study medication or be surgically sterile.
Acceptable contraceptive methods for female (need at least two):
a. Hormonal methods of contraception (including oral and transdermal contraceptives, injectable progesterone, progestin subdermal implants, progesterone-releasing IUDs) at least 14 days prior to the first dose of trial medication;
b. Abstinence;
c. Placement of a copper-containing intrauterine device (IUD);
d. Condom with spermicidal foam/gel/film/cream/suppository;
e. Tubal ligation;
f. Male partner who has had a vasectomy for at least 4 months. Acceptable contraceptive methods for male (need at least one):
a. Abstinence;
b. Use of condom for males with a vasectomy;
c. Without a vasectomy, must use a condom and be instructed that their female partner should use another form of contraception such as an IUD, spermicidal
foam/gel/film/cream/suppository, diaphragm with spermicide, oral contraceptive, injectable progesterone, subdermal implant or tubal ligation if the female partner
could become pregnant from the time of the first dose of trial medication until
3 months after the last dose.
Best corrected visual acuity using ETDRS protocol of 20/40 to 20/320 in the study eye at the baseline visit.
Best corrected visual acuity score in the fellow eye of 20/800 or better at the baseline Visit.
Note: Only one eye will be treated (study eye) during 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.
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. Subject has retinal central subfield thickness ≥250µm measured using Stratus OCT.
5. 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.
6. 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. CNV in either eye of other etiology, eg, ocular histoplasmosis, trauma, or pathologic myopia.
2. Any prior treatment for neovascular AMD including but not limited to the following approved or investigational therapies administered locally to the study eye or systemically; verteporfin photodynamic therapy, focal laser photocoagulation, external-beam radiation therapy, transpupillary thermotherapy in the study eye, anti VEGF therapy eg ranibizumab, pegaptanib, bevasiranib, and VEGF trap, intra ocular(eg, triamcinolone, anecortave acetate), peribulbar steroids, vitrectomy, submacular surgery or other surgical intervention for AMD in the study eye.
3. 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.
4. Presence of subfoveal scarring.
5. Retinal pigment epithelial tear involving the macula in the study eye.
6. History of rhegmatogenous retinal detachment or macular hole (any Stage) in the study eye.
7. 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.
8. Current active intraocular inflammation (grade “trace” or above) or history of idiopathic / autoimmune uveitis in either eye.
9. Current infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye.
10. Vitreous hemorrhage present in the study eye.
11. Spherical equivalent of the refractive error in the study eye demonstrating more than−8 diopters of myopia.
12. Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Baseline.
13. Uncontrolled glaucoma in the study eye (defined as intraocular pressure of 30 mmHg or more despite treatment with antiglaucoma medications).
14. History of glaucoma filtering surgery in the study eye.
15. History of corneal transplant in the study eye.
16. 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.
17. Current treatment for active systemic infection.
18. 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 (baseline visit).
19. History of cerebral vascular accident, myocardial infarction, transient ischemic attacks 6 months prior to study enrollment.
20. Inability to obtain fundus photographs, FFA or OCT of sufficient quality to be analyzed and graded by the central reading center.
21. Inability to comply with study or follow-up procedures. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Mean change from baseline in the best corrected visual acuity score measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol by Week 16. |
|
| 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
| 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 | 2 |
| 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
|
| End of Trial in all participating countries is defined as Last Subject Last Visit. |
|
| 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 | 1 |
| E.8.9.1 | In the Member State concerned days | 14 |
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial days | 14 |
Print
