Clinical Study to Investigate Safety and Efficacy of GSK933776 in Adult Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration

GlaxoSmithKline191 enrolled

Overview

The purpose of this study is to determine the safety and efficacy of GSK933776 in the treatment of geographic atrophy secondary to age-related macular degeneration.

This is a Phase 2a proof of concept study designed to evaluate the safety and efficacy of GSK933776 for the treatment of geographic atrophy secondary to age-related macular degeneration. This is a placebo-controlled parallel-group study that is double masked.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

191

Conditions

Atrophy, Geographic

Interventions

GSK933776DRUG

GSK933776

PlaceboDRUG

Placebo

Eligibility

Sex: ALLMin age: 55 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adult patients ≥55 years of age inclusive * Evidence of AMD confirmed by the presence of at least 1 druse ≥125 μm diameter * Well-demarcated GA due to AMD of total area 1.9-17 mm2 measured in the study eye * Best-corrected visual acuity score of ≥ 35 letters (approximately 20/200 Snellen VA equivalent or better) in the study eye Exclusion Criteria: * Additional eye disease in the study eye that could compromise assessment of best-corrected visual acuity or imaging of the posterior pole * History of CNV secondary to AMD in the study eye * Any previous treatment for AMD in the study eye, approved or investigational, with the exception of dietary supplements * Risk of cerebrovascular disease, cerebral hemorrhage or stroke * History of systemic autoimmune disease * Use of platelet anti-aggregants or anti-coagulants (aspirin up to 325 mg/day is allowable, or in subjects allergic or intolerable to aspirin, clopidogrel up to 75 mg/day is allowable) * Use of chronic corticosteroids * Uncontrolled hypertension in spite of antihypertensive medications * Renal or hepatic insufficiency or clinically significant anemia * More than moderate MRI white matter changes

Locations (41)

Outcomes

Primary Outcomes

Change From Baseline in the Area of Geographic Atrophy (GA) Assessed by Color Fundus Photographs (FP) in the Study Eye

Atrophic age-related macular degeneration (AMD) also called GA is characterized by thinning of the retinal pigment epithelium (RPE) and underlying choriocapillaris, as well as overlying photoreceptors in the macula. GA was evaluated by color FP at the indicated time points: screening, 6 months, 12 months and 18 months. Change from BL: (screening, month 6, 12 or 18 value minus BL value. Note screening occurs prior to BL). Only participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Efficacy Population: all participants in the Intent-to-Treat (ITT) Population who met the protocol defined inclusion criterion for area of GA assessed by color FP in the study eye in at least one visit from screening visit through BL visit, inclusive and had data of area of GA assessed by fundus autofluorescence images in the study eye for at least 75% of the visits (\>=14 visits) from post-BL treatment month 2 visit to treatment month 19 visit.

Time frame: Baseline (BL), 6 months, 12 months and 18 months

Number of Participants With Ocular or Non-ocular Adverse Events (AEs) During the Treatment Period

An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. It includes:1. Any abnormal laboratory test results or other safety assessments including those that worsen from Baseline, and felt to be clinically significant in the medical and scientific judgment of the Investigator 2.Exacerbation (increase in frequency/intensity) of a chronic or intermittent pre-existing condition 3. New conditions detected or diagnosed after screening visit 4. Signs, symptoms, or the clinical sequelae of a suspected interaction/suspected overdose of investigational product or a concomitant medication. AEs were presented as non-ocular and ocular AEs.

Time frame: Up to 21 months

Number of Participants With Ocular or Non-ocular Serious Adverse Events (SAEs) During the Treatment Period

Time frame: Up to 21 months

Number of Participants With Vital Signs of Potential Clinical Importance (PCI) During the Treatment Period: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Data from ClinicalTrials.gov

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GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Phoenix, Arizona, United States

GSK Investigational Site

Arcadia, California, United States

GSK Investigational Site

Irvine, California, United States

GSK Investigational Site

La Jolla, California, United States

GSK Investigational Site

Los Angeles, California, United States

GSK Investigational Site

Palm Desert, California, United States

GSK Investigational Site

San Francisco, California, United States

GSK Investigational Site

Torrance, California, United States

GSK Investigational Site

Golden, Colorado, United States

...and 31 more locations

Number of Participants With Abnormal Laboratory Parameter Values of Potential Clinical Importance (PCI)

The following laboratory parameters were assessed: Hematology: Platelet Count, Red Blood Cell Count, White Blood Cell (WBC) Count, Reticulocyte Count, Hemoglobin, Hematocrit, Prothrombin time-International Normalized Ratio, Activated partial thromboplastin time, Mean corpuscular volume, Mean corpuscular haemoglobin, Mean corpuscular hemoglobin concentration, Neutrophils (ANC), Lymphocytes, Monocytes, Eosinophils, and Basophils. Clinical chemistry: Blood urea nitrogen, Potassium, Aspartate aminotransferase, Total and direct bilirubin Creatinine, Chloride, Alanine aminotransferase, Uric Acid, Glucose (fasting), Total Carbon dioxide , Gamma glutamyltransferase, Albumin, Sodium, Calcium, Alkaline phosphatase, Total Protein, and HbA1c. Urine: Specific gravity, pH, glucose, protein, blood and ketones and Microscopic examination. Only those with PCIs are displayed.

Time frame: At any point from Baseline through follow-up visit.

Secondary Outcomes

Change From Baseline in Area of GA Assessed by Fundus Autofluorescence Images (hypoAF) Corresponding to GA in Study Eye

Atrophic AMD also called as GA is characterized by thinning of the retinal pigment epithelium (RPE) and underlying choriocapillaris, as well as overlying photoreceptors in the macula. GA was evaluated by fundus autofluorescence images in the study eye at the indicated time points: screening, 6 months, 12 months and at 18 months. Change from Baseline: (months 6, 12,18 value minus Baseline value, respectively. Note screening occurs before baseline). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Time frame: Baseline, 6 months, 12 months and 18 months

Change From Baseline in Area of Total hypoAF in Study Eye

Atrophic AMD also called as GA is characterized by thinning of the retinal pigment epithelium (RPE) and underlying choriocapillaris, as well as overlying photoreceptors in the macula. GA was evaluated by fundus autofluorescence at the indicated time points: screening, 6 months, 12 months and at 18 months. Change from Baseline: (Month 6, 12, 18 value minus Baseline value, respectively. Note screening occurs before baseline). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Time frame: Baseline, 6 months, 12 months and 18 months

Number of Participants Losing Letters in Early Treatment Diabetic Retinopathy Study (ETDRS)-Best Corrected Visual Acuity (BCVA) Score at Month 12 and Month 18 for Each Eye

Participants enrolled into the study were required to have a best-corrected ETDRS visual acuity score of at least 35 letters as determined by ETDRS-BCVA evaluation. ETDRS-BCVA score was assessed at the indiated time points at: Month 12 and Month 18 with categorical changes in the number of participants losing \>30, \>=15, \>=10, \>=5 and \<5 letters.

Time frame: Month 12 and Month 18

Mean Change in ETDRS-BCVA Score From Baseline at Every Month up to Month 18

Participants enrolled into the study were required to have a best-corrected ETDRS visual acuity score of at least 35 letters as determined by ETDRS-BCVA evaluation. ETDRS-BCVA score was assessed as change from baseline in the mean best-corrected ETDRS visual acuity score at 18 months. Change from Baseline is defined as post-dose visit value minus Baseline value. Note that screening occurs before baseline. Values were truncated to one decimal place and negative sign retained where value is negative and the truncated value is zero. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Time frame: Baseline and every month up to Month 18

Area Under the Plasma Concentration-time Curve From Time 0 to the End of Dosing Interval at Steady-state (AUC0-28d) of GSK933776 in Geographic Atrophy Participants

Area under the plasma concentration-time curve from time 0 to the end of dosing interval at steady-state; derived from dose and clearance parameters was evaluated. Blood samples were collected at the indicated time points on Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476.