A 12-Week Study of Eye Drops to Treat Wet Age-related Macular Degeneration (AMD)

• Conditions: Age-related macular degeneration (AMD); MedDRA version: 14.0Level: PTClassification code 10025409Term: Macular degenerationSystem Organ Class: 10015919 - Eye disorders; Therapeutic area: Body processes [G] - Ocular Physiological Phenomena [G14]

• Registration Number: EUCTR2011-000243-24-DE
• Lead Sponsor: GlaxoSmithKline Research & Development Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-04-26
• Last Update Posted: 3 December 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria:
1. 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.)
2. 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 fluorescence 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
3. 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
4. Gender and age: Subject is a male or female adult 50 years of age or older.
5. 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.
6. Study Compliance: Subject is able and willing to comply with the study requirements and is able and willing to attend all scheduled visits.
7. 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%).
8. QT interval: Subject has a QTcF value < 450 msec, or < 480 msec for subjects with Bundle Branch Block. [Note: subjects with paced rhythms may be considered pending discussion with the medical monitor.]
Specific information regarding warnings, precautions, contraindications, adverse events, and other pe

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
Study Eye:
1. 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)
2. CNV in the study eye due to other causes unrelated to age-related macular degeneration
3. Presence of retinal angiomatous proliferation (RAP) in the study eye, as determined by the investigator (confirmation by indocyanine green angiography is not required)
4. Geographic atrophy involving the center of the fovea in the study eye
5. 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
6. Vitreous, subretinal or retinal hemorrhage in the study eye that is unrelated to AMD
7. Presence of an RPE tear in the study eye
8. Aphakia or total absence of the posterior capsule (Yttrium aluminum garnet (YAG) capsulotomy permitted) in the study eye
9. History of vitrectomy in the study eye
10. Intraocular surgery in the study eye within 3 months prior to treatment
11. Any previous treatment in the study eye for neovascular AMD, approved or investigational
Fellow Eye:
12. Current intravitreal anti-VEGF therapy in the fellow eye
13. Best-corrected visual acuity score by electronic ETDRS < 56 letters in the fellow eye at screening
Concurrent Conditions or Concomitant Medications:
14. Subject has uncontrolled glaucoma (intraocular pressure > 25 mmHg) despite treatment with anti-glaucoma medication.
15. A known, positive test for Hepatitis B surface antigen or Hepatitis C antibody within 3 months of screening
16. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
17. Active bleeding disorder or a history of hemoptysis, cerebral or clinically significant gastrointestinal hemorrhage within 6 months of screening
18. Significant uncontrolled or unstable cardiovascular, nervous system, pulmonary, renal, endocrine, or gastrointestinal disease for example:
• Uncontrolled diabetes mellitus, with hemoglobin A1c (HbA1c) > 10%
• Myocardial infarction or stroke within 6 months of screening
• Major surgery within 3 months of screening
• Clinically relevant thyroid disease
19. Uncontrolled hypertension:
Systolic blood pressure > 160 mmHg
Diastolic blood pressure > 100 mmHg
Note: Initiation or adjustment of antihypertensive medications is permitted prior to study entry provided the referenced criteria are met (See Section 4.4.3).
20. Subject has a history within the past 2 years of alcohol or substance abuse, or psychiatric disorder likely to confound the efficacy or safety assessments.
21. Known HIV infection
22. Within 6 months prior to the Screening Visit, use of any systemically administered anti angiogenic agent (e.g., bevacizumab, sunitinib, cetuximab, sorafenib, pazopanib), approved or investigational
23. Within 6 months prior to the Screening Visit, use of medications known to be toxic to the retina, lens or optic nerve (e.g. desferoximine, chloroquine/hydrochloroquine, chlorpromazine, phenothiazines, tamoxifen, and ethambutol)
24. Use of systemic steroids (>10 mg prednisone or equivalent/day) within 14 days of the start of treatment
25. Use of prohibited m

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified