E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Age-Related Macular Degeneration |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
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 evaluate if pazopanib eye drops can maintain or possibly improve vision, while reducing the continued need for intravitreal injections. |
|
E.2.2 | Secondary objectives of the trial |
1. To compare safety and tolerability between each pazopanib arm and comparator arms. 2. To compare retinal anatomical changes between each pazopanib arm and comparator arms. 3. To determine the steady-state plasma pazopanib concentrations after topical ocular administration. 4. To evaluate the response by complement factor H Y402H genotypes in each pazopanib arm and comparator arms. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Eligibility criteria 5-9 apply to the study eye only. 1. Subject understands the procedures, agrees to participate in the study (including participation in the CFH Y402H pharmacogenetics research), and has signed and dated the informed consent form prior to the initiation of any study-related activities. If the subject is unable to read or sign the consent form due to visual impairment, then alternate approaches may be followed. 2. Subject is a male or female adult 50 years of age or older. 3. Female subject is of non-childbearing potential defined as being physiologically incapable of becoming pregnant. 4. Subject is able and willing to comply with the study requirements (for example, able to open the eye drop foil-wrap packaging and eye drop vials, willing to adhere to the daily dosing schedule for the treatment duration), anticipates remaining in local vicinity for duration of trial, and is able and willing to attend all scheduled visits. 5. At the Screening Visit, subject has an active subfoveal CNV lesion secondary to AMD that is in need of re-injection. 6. At the Screening Visit, the total lesion area is <=12 disc areas with CNV contributing >=50% of the total lesion area. Serous retinal pigment epithelial detachment (PED), fibrosis, atrophic scar and subretinal hemorrhage combined are <50% of the total lesion area. Fibrosis alone is <=25% of the total lesion area. If the subretinal hemorrhage involves the fovea, then subfoveal hemorrhage is <=1 disc area. 7. Subject has the following anti-VEGF intravitreal injection history: a. At least 3 pre-screening anti-VEGF injections . At least 2 of the pre-screening injections must have occurred in the past 6 months. This may include subjects who were first treated as recently as 3 months prior to screening. b. Previous response to anti-VEGF injection therapy, which is defined as a meaningful reduction (at least 50 microns) in center point thickness or equivalent field for given OCT machine. c. Investigator anticipates the subject has a continued need for and is expected to benefit from anti-VEGF therapy. 8. At the Screening Visit, subject has best corrected VA in the study eye of 24 to 78 letters, inclusive, using the Early Treatment of Diabetic Retinopathy Study (ETDRS) grading charts. This calculated letter range equates to approximately 20/32 to 20/320 Snellen VA equivalents. 9. Subject has ocular media and pupillary dilation that permits adequate quality fundus imaging. 10. Subject has liver chemistry findings prior to randomization that are within normal limits or clinically insignificant. 11. Subject has a QTcb or QTcf (QT interval corrected for heart rate according to Bazett’s or Friederica’s formula, respectively) value <450 msec, or <480 msec for subjects with Bundle Branch Block, based on ECG testing during the Screening Period or within 3 months prior to the Screening Visit. |
|
E.4 | Principal exclusion criteria |
1. Subject has ever been treated in the study eye with IVT steroids, investigational (i.e., unapproved) drugs for CNV (exception: bevacizumab is permitted), pazopanib, investigational devices for CNV, previous subfoveal or juxtafoveal focal laser photocoagulation, photodynamic therapy with verteporfin, radiation or transpupillary thermotherapy, history of submacular surgery or other surgical intervention for AMD. 2. Subject has a history in the study eye of vitrectomy surgery, scleral buckle, glaucoma filtering/shunt surgery, or corneal transplant. Prior cataract surgery and prior Nd:YAG (neodymium-doped yttrium aluminium garnet) laser posterior capsulotomy for treatment of posterior capsule opacification are permitted if performed more than 3 months prior to Screening Visit and a posterior chamber intraocular lens is in place. 3. Within 6 months prior to the Screening Visit, the subject has received treatment with any systemically administered anti angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib). 4. Within 6 months prior to the Screening Visit, the subject has received treatment with medications known to be toxic to the eye (e.g., desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, nicotinic acid, and ethambutol). 5. Subject has center-fovea involvement of any of the following: fibrosis, atrophy, PED, or retinal pigment epithelial tear. Subject has CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia. 6. Concurrent Ocular Conditions (specific to study eye unless stated): a. Subject is unwilling to refrain from wearing contact lenses starting b. Subject has clinical evidence of diabetic retinopathy or diabetic macular edema. c. Subject has any concurrent intraocular condition that could require medical or surgical intervention during the study or likely lead to clinically significant effect in VA or retinal thickness. d. Subject has active or recent (within 4 weeks) intraocular inflammation. e. Subject has current vitreous hemorrhage. f. Subject has a history of rhegmatogenous retinal detachment or macular hole (stage 2 or greater). g. Subject has an active allergic or infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. h. Subject has a spherical equivalent of the refractive error demonstrating more than 8 diopters of myopia. For a subject who has undergone prior refractive or cataract surgery the preoperative refractive error cannot exceed 8 diopters of myopia. i. Subject has uncontrolled glaucoma (intraocular pressure >25 mmHg) despite treatment with antiglaucoma medication. j. Subject is unable to be photographed to document CNV due to cataract obscuring the CNV, known allergy to fluorescein, or lack of venous access, or other reasons. k. Subject has other ocular disease or progressive retinal disease likely to affect VA during the study. l. Subject is aphakic. m. Subject is phakic or pseudophakic with evidence of instability of the intraocular lens (e.g., zonular dehiscence or weakness, displaced lens, vitreous prolaps). n. Subject has a history of idiopathic or autoimmune-associated uveitis. 7. Concurrent Systemic Conditions: Subject has significant uncontrolled or unstable cardiovascular, nervous system, pulmonary, renal, endocrine, or gastrointestinal disease. In addition, a subject is excluded for the following conditions: a. Subject has had a myocardial infarction or cerebrovascular accident within 6 months prior to the Screening Visit. b. Subject has mean blood pressure ≥150/95 mmHg, with or without antihypertensive medication(s). c. Subject has unstable liver disease or known biliary abnormalities (with the exception of Gilbert’s syndrome, or asymptomatic gallstones), presence of hepatitis B surface antigen, or positive hepatitis C test result within 3 months of the Screening Visit. d. Subject is receiving current treatment for active systemic infection or has a history of recurrent significant infections. e. Subject has had an active bleeding disorder or a history of hemoptysis, cerebral or clinically significant gastrointestinal hemorrhage within 6 months of the Screening Visit. f. Subject has had major surgery within 1 month of the Screening Visit. g. Subject has received an allogeneic bone marrow transplant. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in BCVA as measured by the number of letters read on the ETDRS grading charts at a starting distance of 4 meters at Week 52. |
|
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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 25 |
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 | 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
|
End of study is defined as the last visit for the last subject |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 14 |