GSK Geographic Atrophy


Status: Active, not recruiting
Keywords: macular degeneration , dry AMD , geographic atrophy
IRB Number: 00049675
Specialty: Ophthalmology, Ophthalmology, Ophthalmology
Sub Specialties: Retinal Diseases, Geriatric Ophthalmology,

Brief Summary

The objective of this study is to evaluate the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of GSK933776 when administered by monthly intravenous (IV) infusion to patients with geographic atrophy.

The specific aims are to assess the effects of GSK933776 on the rate of change in the area of geographic atrophy and to assess the safety and tolerability of GSK933776; to evaluate its effects on visual acuity and to determine its pharmacokinetic and pharmacodynamic profiles in GA patients; to evaluate its effects on visual function and on macular anatomy, and to explore the change in subject-reported visual function outcomes.

Principal Investigator: Paul Bernstein
Department: Ophthalmology-Services
Co Investigator: Albert Vitale
Co Investigator: Jeffrey Anderson
Co Investigator: Kimberley Wegner
Co Investigator: Mary Elizabeth Hartnett
Co Investigator: Mike Teske

Contact Information

Name:Katie Farnsworth
Phone: 801-585-6647

Inclusion Criteria

• Adult patient ≥55 years of age at the time of signing the informed consent.
• A female subject is eligible to participate if she is of:
o non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/mL and estradiol < 40 pg/mL (<140 pmol/L) is confirmatory).
o childbearing potential and agrees to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until 3 months after last dose of study medication.

• Male subjects must agree to use one form of acceptable contraception methods if their partner is of childbearing potential (as defined above). This criterion must be followed from the time of the first dose of study medication until 3 months after last dose of study medication.

• Evidence of age-related macular degeneration confirmed by the presence of at least 1 drusen ≥125 μm diameter in either eye.

• Well-demarcated geographic atrophy due to age-related macular degeneration of total area 1.9-17 mm2 measured on color fundus photographs and fundus autofluorescence in the study eye

• Best-corrected ETDRS visual acuity score (best corrected visual acuity) of ≥ 35 letters (approximately 20/200 Snellen VA equivalent) in the study eye. If both eyes are eligible for the study, the eye with the better best corrected visual acuity score is selected.

• Capable of giving written informed consent, which includes compliance with the requirements of the protocol and restrictions listed in the consent form.

Exclusion Criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• Additional eye disease in the study eye that could compromise assessment of best corrected visual acuity, confound best corrected visual acuity assessment, or imaging of the posterior pole

• History of neovascular age-related macular degeneration in the study eye requiring treatment.

• Any previous treatment in the study eye for any form of age-related macular degeneration, approved or investigational, with the exception of dietary supplements

• Intraocular surgery in the study eye within 3 months of dosing or anticipated during the course of the study

• Uncontrolled intraocular pressure > 25 mm Hg in the study eye despite treatment with glaucoma medication.

• Use of medications known to be toxic to the retina, lens or optic nerve 6 months prior to screening visit

Non Ocular

• Known risk or history of:
a. Central nervous system (CNS) disorders.
i. History and/or evidence (CT or MRI scan performed within the past 12 months or during screening period) of cerebrovascular disease, (cerebrovascular accident, cerebral hemorrhage), structural or developmental abnormality, epilepsy, infectious, degenerative or inflammatory/demyelinating CNS conditions (e.g. Alzheimer’s disease and/or diagnosis of dementia, multiple sclerosis, Parkinson's disease, vasculitis) or any other condition that the investigator and/or the medical monitor considers as a relevant risk factor for intracerebral haemorrhage.
ii. Transient ischemic attack (TIA)/cerebrovascular accident (CVA) in the last year, or other uncontrolled risk factors for stroke.

b. History of seizures (except febrile seizures in childhood) or recent unprovoked seizure
c. Type 1 or uncontrolled type 2 diabetes mellitus, active cardiovascular disease (e.g., moderate-severe angina, unstable angina, myocardial infarction (MI) within the last 2 years, symptomatic heart failure, clinically significant arrhythmia.
d. Other severe/progressive medical or neurological conditions that limit the subject's ability to complete or safely participate in the trial.
e. Current blood clotting or bleeding disorder or conditions that predispose to these (e.g. cancer)
f. Current clinically significant systemic illness or significant infection within 30 days (e.g. chronic persistent or acute infection) that is likely to result in deterioration of the subject's condition or affect the subject's safety during the study.
g. Hepatobiliary abnormalities or disease (with the exception of Gilbert's syndrome or asymptomatic gallstones)
h. Diagnosis of currently active, or, in remission ut chronic relapsing systemic autoimmune disease or condition (e.g. multiple sclerosis, lupus erythematosis et) that the investigator and/or the medical monitor considers as a relevant risk factor for concomitant administration of a therapeutic monoclonal antibody.
i. Any other condition that the investigator and/or the medical monitor considers as a relevant risk factor or other clinically significant abnormality on physical, laboratory, ECG examination (e.g. atrial fibrillation) that would be detrimental to the subject
• Subject should have ability to comply with procedures for magnetic resonance imaging (MRI) Patients must be excluded if:
a. Contraindications for MRI are known: including cardiac pacemaker, CNS neurostimulator, aneurysm clips, artificial heart valves, other metal foreign body, claustrophobia.
b. A Screening/Baseline brain MRI indicates any of the following conditions:
i. evidence of other CNS conditions listed above
ii. shows more than minimal vascular changes
iii. Screening/baseline MRI shows five or more microhemorrhage related events (ARIA-H), formerly characterized as microhemorrhage/microbleeds (longest diameter less than 5 mm)
iv. Screening/Baseline MRI shows more than moderate whtie matter changes
• Prior allergic reactions to biological products (vaccines, antibodies) or known hypersensitivity to any of the components of the drug
• Prior participation in clinical investigations involving therapeutic monoclonal antibodies or proteins derived from monoclonal antibodies or any investigations of treatments or use of any other investigational medication or device within 2 months prior to screening or within 5 half-lives of use of such a medication prior to screening, whichever is longer
• Use of drugs with thrombolytic therapy or with platelet anti-aggregant or anti-coagulant properties (excluding the use of aspirin 325 mg/day or less, or in subjects allergic to or intolerant of aspirin, clopidogrel 75 mg/day or less). The combination of aspirin and clopidogrel is not allowed, as this combination has been shown to increase the risk of hemorrhage
• With the exception of low doses (a daily dose less than or equal to 10 mg prednisone or equivalent) of corticosteroids, the use of systemic (defined as oral or intravenous) corticosteroids, or any use of other prolonged immunosuppressants 30 days or less prior to screening is prohibited.
• Positive pre-study drug or alcohol screen, except where subject has a prescription for pain or anxiolytic medication or that would prospectively cause a positive result. The investigator should consult medical monitor with patient history before screening if known that patient coudl have positive test. Current or recent drug or alcohol abuse or dependence. History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (~240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. Use of illegal drugs and/or any clinically significant side effects attributable to the drug that, in the opinion of the investigator, would preclude participation in the trial
• Sitting systolic blood pressure > 170 mmHg or sitting diastolic blood pressure of > 100 mmHg at the time of screening
• QTc > 450 millisecond (msec) or > 480 msec for subjects with Bundle Branch Block at the time of screening.
Note: If the ECG at screening indicated a QTc interval outside these limits, two further ECGs should be performed and the average QTc value of these triplicate ECGs calculated. If the average value exceeds the stated limits, the subject is not eligible.
• Positive Hepatitis B surface antigen or Hepatitis C antibody test at Screen
• AST and ALT ≥ 2xULN; alkaline phosphatase and bilirubin  1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
• Abnormal creatinine (more than 1.5 ULN) or estimated calculated creatinine clearance (less than 30 ml/min) or clinically significant abnormalities on screening urinalysis
• Clinically significant anemia based on age appropriate