A Phase 2b Dose-Finding Study of Pazopanib Eye Drops versus Ranibizumab Injections for the Treatment of Neovascular Age-Related Macular degeneration - ND
- Conditions
- eovascular age-related macular degeneration.MedDRA version: 12.1Level: LLTClassification code 10025409Term: Macular degenerationNeovascular age-related macular degeneration.
- Registration Number
- EUCTR2009-015106-19-IT
- Lead Sponsor
- GlaxoSmithKline Research and Development
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 450
1. Subject understands the procedures, agrees to participate in the study (including participation in the CFH Y402H pharmacogenetics research 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, 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. b. Previous response to anti-VEGF injection therapy, which is defined as a meaningful reduction in center point thickness or equivalent field 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, ETDRS grading charts. This calculated letter range equates to approximately 20/32 to 20/320 Snellen VA equivalents. 9. Subject has clear ocular media and adequate pupillary dilation to permit good 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.
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
;
1. Subject understands the procedures, agrees to participate in the study (including participation in the CFH Y402H pharmacogenetics research 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, 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. b. Previous response to anti-VEGF injection therapy, which is defined as a meaningful reduction in center point thickness or equivalent field 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, ETDRS grading charts. This calculated letter range equates to approximately 20/32 to 20/320 Snellen VA equivalents. 9. Subject has clear ocular media and adequate pupillary dilation to permit good 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.
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
Subject has ever been treated in the study eye with intravitreal steroids, radiation, investigational drugs for CNV (exception: bevacizumab is permitted), pazopanib, investigational devices for CNV, or photodynamic therapy with verteporfin. 2. Subject has a history in the study eye of vitrectomy surgery, scleral buckle, or glaucoma filtering/shunt surgery. Prior cataract surgery is permitted if more than 3 months prior to Screening Visit and a posterior chamber intraocular lens is in place. 3. Subject is receiving concurrent treatment with any systemically administered anti angiogenic agent. 4. Subject is receiving concurrent treatment with medications known to be toxic to the retina, lens or optic nerve. 5. Subject has center-fovea involvement of any of the following )specific to study eye): fibrosis, geographic 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 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. k. Subject has other ocular disease or progressive retinal disease likely to affect VA during the study. 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 an active bleeding disorder. f. Subject has had major surgery within 1 month of the Screening Visit. g. Subject has received an allogeneic bone marrow
;
Subject has ever been treated in the study eye with intravitreal steroids, radiation, investigational drugs for CNV (exception: bevacizumab is permitted), pazopanib, investigational devices for CNV, or photodynamic therapy with verteporfin. 2. Subject has a history in the study eye of vitrectomy surgery, scleral buckle, or glaucoma filtering/shunt surgery. Prior cataract surgery is permitted if more than 3 months prior to Screening Visit and a posterior chamber intraocular lens is in place. 3. Subject is receiving concurrent treatment with any systemically administered anti angiogenic agent. 4. Subject is receiving concurrent treatment with medications known to be toxic to the retina, lens or optic nerve. 5. Subject has center-fovea involvement of any of the following )specific to study eye): fibrosis, geographic 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 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. k. Subject has other ocular disease or progressive retinal disease likely to affect VA during the study. 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 an active bleeding disorder. f. Subject has had major surgery within 1 month of the Screening Visit. g. Subject has received an allogeneic bone marrow
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method