12 Week Patient Study in Neovascular Age-related Macular Degeneration (AMD)

NCT01362348 | Terminated Phase 2 Results

• 1 other identifier: 114987
• Study Type: interventional
• Target: 19
• Locations: 3 countries
• Sites: 15

Brief Summary

The purpose of this 12 week, open-label study is to investigate the safety and efficacy of a single dose regimen of pazopanib eye drop for neovascular AMD.

Conditions

Macular Degeneration

Keywords

Age-related Macular Degeneration

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Central Retinal Lesion Thickness (CRT) as Measured by Optical Coherence Tomography (OCT) at Day 29

  CRT was the distance between the inner limiting membrane of the retina and the inner border of the retinal pigment epithelium/choriocapillaris band, inclusive of sub retinal fluid, measured in the central 1 millimeter (mm) of the Cube scan. OCT assessments were performed using SPECTRALIS spectral domain OCT. Images were evaluated by investigator for safety monitoring, and by a central reading center for eligibility determination and pharmacodynamics (PD) effects. Observed case (OC) data set was used for analysis in this analysis dataset, a missing assessment at any scheduled time point was considered unevaluable, was not imputed and was not included in data analysis. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the baseline value from the individual post-randomization value at Day 29.

  Baseline (Week 0) and Day 29

• Change From Baseline in Best Correct Visual Acuity (BCVA) as Measured by the Number of Letters Determined by Electronic Early Treatment Diabetic Retinopathy [ETDRS] Study Visual Acuity (EVA) at Day 29

  BCVA was measured in the study eye using the EVA chart starting at a test distance of 4 meters. The BCVA score is the number of letters read correctly by the participant. A decrease in the BCVA score indicates a worsening of vision while higher scores indicates improvement of VA. Baseline was defined as the assessments performed between Day -3 to -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-randomization value at Day 29.

  Baseline (Day -3 to -1) and Day 29

Secondary Outcomes (12)

• Change From Baseline in Central Retinal Lesion Thickness (CRLT) Over Time

  Baseline (Week -3 to -1) Up to Follow-up (Day 102)

• Change From Baseline in Intraretinal (IR) or Subretinal (SR) Fluid Thickness, Intraretinal Cysts or Serous Retinal Pigment Epithelial Detachment (PED Thickness) Over Time

  Baseline (Week -3 to -1) Up to Follow-up (Day 102)

• Change From Baseline in BCVA Over Time

  Baseline (Week -3 to -1) Up to Follow-up (Day 102)

• Change From Baseline in the Area of Choroidal Neovascular (CNV) Size and CNV Total Lesion Complex Size as Measured by Fluorescein Angiography (FA) at Day 29

  Baseline (Day -3 to -1) and Day 29

• Number of Participants With Change in Charactertsics (Atrophy, Pigment, SR Hemorrhage, IR Hemorrhage, SR Fluid and Fibrosis) as Measured by FP

  Day 29

Study Arms (1)

pazopanib eye drops

EXPERIMENTAL

pazopanib topical ocular administration

Drug: pazopanib eye drops

Interventions

pazopanib eye drops DRUG

10 mg/mL (1 drop) four times daily

pazopanib eye drops

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects eligible for enrolment in the study must meet all of the following criteria:
• Consent: Subject understands the procedures, agrees to participate in the study (including participation in the CFH Y402H pharmacogenetic 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 the consent form due to visual impairment then the consent must be read to the subject verbatim by the person administering the consent, a family member, or legally acceptable representative. (Note: Consent by legally acceptable representative is allowed where this is in accordance with local laws, regulations, and ethics committee policy.)
• Age-related macular degeneration: For each subject enrolled in the study, only one eye (study eye) will be treated, and eligibility criteria apply to the study eye. All of the following characteristics are required and must be confirmed by the central reading center:
• CNV caused by AMD that extends under the geometric center of the foveal avascular zone
• Center subfield thickness (inclusive of subretinal fluid) \> 320 microns on OCT \[SPECTRALIS® (Heidelberg)\]
• Total lesion area ≤12 disc areas on fluorescein angiography, where the lesion complex includes CNV, blood, blocked florescence not from blood, and serous detachment of the retinal pigment epithelium
• CNV comprises \< 50% of lesion area
• classic CNV comprises \< 50% of the lesion area
• fibrosis comprises ≤ 25% of lesion area
• if no evidence of classic CNV, then presumed to have recent disease progression based on deterioration (≥ 5 letter decrease in vision or evidence of growth of a CNV lesion on fluorescein angiography ) within the last 3 months or evidence of hemorrhage from CNV
• Visual acuity: Best-corrected visual acuity score by electronic ETDRS in the study eye of between 25 and 73 letters (approximately equivalent to Snellen VA of 20/320 to 20/32) at screening
• Gender and age: Subject is a male or female adult 50 years of age or older.
• Non-childbearing potential: Female subject is of non-childbearing potential defined as being physiologically incapable of becoming pregnant. This includes any female who is post-menopausal (12 months of spontaneous amenorrhea) or who is surgically post-menopausal (via documented hysterectomy or bilateral tubal ligation). In questionable cases of postmenopausal status, a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 MIU/mL and estradiol \<40 pg/mL (\<140 pmol/L) \[or equivalent values based on local laboratory criteria\] is confirmatory. Refer to the SPM for more information.
• Study Compliance: Subject is able and willing to comply with the study requirements and is able and willing to attend all scheduled visits.
• Liver function tests: Subject has liver chemistry values that are within normal limits or clinically insignificant as evidenced by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<2xULN; alkaline phosphatase and bilirubin \<1.5xULN (isolated bilirubin \>1.5xULN is acceptable, if bilirubin is fractionated and direct bilirubin is \< 35%).

You may not qualify if:

• Subjects meeting any of the following criteria must not be enrolled in the study:
• Study Eye:
• Additional eye disease in the study eye that could compromise best-corrected visual acuity (e.g. glaucoma with documented visual field loss, clinically significant diabetic retinopathy, ischemic optic neuropathy, infection or retinitis pigmentosa)
• CNV in the study eye due to other causes unrelated to age-related macular degeneration
• Presence of retinal angiomatous proliferation (RAP) in the study eye, as determined by the investigator (confirmation by indocyanine green angiography is not required)
• Geographic atrophy involving the center of the fovea in the study eye
• Anterior segment and vitreous abnormalities in the study eye that would preclude adequate observation of the fundus for photographs, fluorescein angiography and spectral-domain OCT
• Vitreous, subretinal or retinal hemorrhage in the study eye that is unrelated to AMD
• Presence of an RPE tear in the study eye
• Aphakia or total absence of the posterior capsule (Yttrium aluminum garnet (YAG) capsulotomy permitted) in the study eye
• History of vitrectomy in the study eye
• Intraocular surgery in the study eye within 3 months prior to treatment
• Any previous treatment in the study eye for neovascular AMD, approved or investigational
• Fellow Eye:
• Current intravitreal anti-VEGF therapy in the fellow eye

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Phoenix, Arizona, 85014, United States

Location

GSK Investigational Site

Miami, Florida, 33143, United States

Location

GSK Investigational Site

Winter Haven, Florida, 33880, United States

Location

GSK Investigational Site

Decatur, Georgia, 30030, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Grand Rapids, Michigan, 49525, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44195, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Paris, 75475, France

Location

GSK Investigational Site

Paris, 75571, France

Location

GSK Investigational Site

Munich, Bavaria, 80336, Germany

Location

GSK Investigational Site

Bonn, North Rhine-Westphalia, 53127, Germany

Location

GSK Investigational Site

Münster, North Rhine-Westphalia, 48145, Germany

Location

GSK Investigational Site

Leipzig, Saxony, 04103, Germany

Location

Related Publications (1)

• Singh R, Wurzelmann JI, Ye L, Henderson L, Hossain M, Trivedi T, Kelly DS. Clinical evaluation of pazopanib eye drops in healthy subjects and in subjects with neovascular age-related macular degeneration. Retina. 2014 Sep;34(9):1787-95. doi: 10.1097/IAE.0000000000000179.

  PMID: 24896137 DERIVED

MeSH Terms

Conditions

Macular Degeneration

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2011
• First Posted: May 30, 2011
• Study Start: July 7, 2011
• Primary Completion: April 16, 2012
• Study Completion: April 16, 2012
• Last Updated: September 21, 2017
• Results First Posted: August 21, 2017

Record last verified: 2017-08

Locations

FR (2); US (9); DE (4)