A Phase 2b Dose-Evaluation Study of Pazopanib Eye Drops versus Ranibizumab Intravitreal Injections for the Treatment of Neovascular Age-Related Macular Degeneratio

Conditions: Age-Related Macular Degeneration
MedDRA version: 12.0Level: LLTClassification code 10064930Term: Age-related macular degeneration

Registration Number: EUCTR2009-015106-19-SE

Lead Sponsor: GlaxoSmithKline Research and Development

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 525

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 anti-VEGF IVT injections prior to the Screening Visit. At least 2 of the pre-screening injections must have occurred in the 6 months prior to the Screening Visit. 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 at least 24 letters using the Early Treatment of Diabetic Retinopathy Study (ETDRS) grading charts. This calculated letter rangeminimum number of letters equates to approximately at least 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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). With the exception of low doses (a daily dose =10 mg prednisone or equivalent) of corticosteroids, the use of systemic (oral, intravenous, intrathecal) corticosteroids or any ocular steroid application to the study eye within 3 months of the Screening Visit is prohibited.
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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate if pazopanib eye drops can maintain or possibly improve vision, while reducing the continued need for intravitreal injections.;Secondary Objective: 1. To compare safety and tolerability between each pazopanib arm and comparator arms.<br>2. To compare retinal anatomical changes between each pazopanib arm and comparator arms.<br>3. To determine the steady-state plasma pazopanib concentrations after topical ocular administration.<br>4. To evaluate the response by complement factor H Y402H genotypes in each pazopanib arm and comparator arms.;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.

Secondary Outcome Measures

Name	Time	Method

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