Clinical trial NCT01342926: Clinical Study to Investigate Safety and Efficacy of GSK933776 in Adult Patients With Geographic Atrophy Secondary to Age-related Macular Degeneration
Official title: A Phase 2, Multi-centre, Randomised, Double-masked, Placebo-controlled, Parallel-group Study to Investigate the Safety, Tolerability, Efficacy, Pharmacokinetics and Pharmacodynamics of GSK933776 in Adult Patients With Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atrophy, Geographic
Keywords: age-related macular degeneration
geographic atrophy
dry AMD
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2011-04-27
Enrollment: 191
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in the Area of Geographic Atrophy (GA) Assessed by Color Fundus Photographs (FP) in the Study Eye
timeFrame: Baseline (BL), 6 months, 12 months and 18 months
measure: Number of Participants With Ocular or Non-ocular Adverse Events (AEs) During the Treatment Period
timeFrame: Up to 21 months
measure: Number of Participants With Ocular or Non-ocular Serious Adverse Events (SAEs) During the Treatment Period
timeFrame: Up to 21 months
measure: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) During the Treatment Period: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Up to 21 months
measure: Number of Participants With Vital Signs of Potential Clinical Importance (PCI) During the Treatment Period: Heart Rate (HR)
timeFrame: Baseline, Month 0, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, Month 9, Month 10, Month 11, Month 12, Month 13, Month 14, Month 15, Month 16, Month 17, Month 18, early withdrawal and at follow-up visit
measure: Number of Participants With 12-lead Electrocardiogram (ECG) of Potential Clinical Importance (PCI)
timeFrame: Baseline, Month 6, Month 12, Month 18, early withdrawal and at follow-up visit
measure: Number of Participants With Abnormal Laboratory Parameter Values of Potential Clinical Importance (PCI)
timeFrame: At any point from Baseline through follow-up visit.
measure: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI)
timeFrame: Month 2, Month 3, Month 4, Month 6, Month 12, Month 18 and at early withdrawal
Secondary outcomes:
measure: Change From Baseline in Area of GA Assessed by Fundus Autofluorescence Images (hypoAF) Corresponding to GA in Study Eye
timeFrame: Baseline, 6 months, 12 months and 18 months
measure: Change From Baseline in Area of Total hypoAF in Study Eye
timeFrame: Baseline, 6 months, 12 months and 18 months
measure: 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
timeFrame: Month 12 and Month 18
measure: Mean Change in ETDRS-BCVA Score From Baseline at Every Month up to Month 18
timeFrame: Baseline and every month up to Month 18
measure: 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
timeFrame: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
measure: Maximum Observed Plasma Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) of GSK933776 in Geographic Atrophy Participants
timeFrame: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
measure: Clearance (CL) of GSK933776 in Geographic Atrophy Participants
timeFrame: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
measure: Estimation of Terminal Phase Half-life (T1/2) of GSK933776 in Geographic Atrophy Participants
timeFrame: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
measure: Volume of Distribution at Steady-state (Vdss) of GSK933776 in Geographic Atrophy Participants Estimated From Population PK Modeling
timeFrame: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
measure: The Pharmacodynamic Effects of GSK933776 Total (Bound and Unbound) Plasma Total Amyloid Beta (Abeta42), and Amyloid Beta Fragments (Abeta18-35), if Possible, Unbound Plasma Aβ Fragments (Abeta1-22)
timeFrame: Baseline, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15 and Month 18
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Arcadia
country: United States
facility: GSK Investigational Site
state: California
city: Irvine
country: United States
facility: GSK Investigational Site
state: California
city: La Jolla
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Palm Desert
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Torrance
country: United States
facility: GSK Investigational Site
state: California
city: Golden
country: United States
facility: GSK Investigational Site
state: Colorado
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Stuart
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Augusta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: New Albany
country: United States
facility: GSK Investigational Site
state: Indiana
city: Leawood
country: United States
facility: GSK Investigational Site
state: Kansas
city: Prairie Village
country: United States
facility: GSK Investigational Site
state: Kansas
city: Louisville
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Paducah
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: North Dartmouth
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Northfield
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Toms River
country: United States
facility: GSK Investigational Site
state: New Jersey
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: West Mifflin
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Ladson
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Abilene
country: United States
facility: GSK Investigational Site
state: Texas
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
city: Galveston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Silverdale
country: United States
facility: GSK Investigational Site
state: Washington
city: Mississauga
country: Canada
facility: GSK Investigational Site
state: Ontario
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: