Atrophy, GeographicPhase 2NCT01342926

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

A Phase 2 study testing GSK933776 in people with Atrophy, Geographic, run by GlaxoSmithKline at 41 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 55 years and older
Conditions the study is for: Atrophy, Geographic
What is being tested?: GSK933776
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 191 participants
Where: 41 sitesin 2 countries
Study dates: 1 Jun 2011to 1 Apr 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 55 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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)

Show all 10Show fewer

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

Trial locations and contacts

41 sites in 2 countries.

Country

City, postcode or hospital

41 sites in 2 countries

United States40 sites

GSK Investigational Site
Abilene, Texas, 79606
GSK Investigational Site
Arcadia, California, 91007
GSK Investigational Site
Augusta, Georgia, 30909
GSK Investigational Site
Austin, Texas, 78705
GSK Investigational Site
Baltimore, Maryland, 21204
GSK Investigational Site
Baltimore, Maryland, 21287
GSK Investigational Site
Boston, Massachusetts, 02111
GSK Investigational Site
Charlottesville, Virginia, 22903
GSK Investigational Site
Detroit, Michigan, 48202
GSK Investigational Site
Galveston, Texas, 77550
GSK Investigational Site
Golden, Colorado, 80401
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Indianapolis, Indiana, 46290
GSK Investigational Site
Irvine, California, 92697
GSK Investigational Site
La Jolla, California, 92037
GSK Investigational Site
Ladson, South Carolina, 29406
GSK Investigational Site
Leawood, Kansas, 66211
GSK Investigational Site
Los Angeles, California, 90033-4500
GSK Investigational Site
Louisville, Kentucky, 40215
GSK Investigational Site
Miami, Florida, 33136
GSK Investigational Site
Nashville, Tennessee, 37203
GSK Investigational Site
New Albany, Indiana, 47150
GSK Investigational Site
New York, New York, 10003
GSK Investigational Site
North Dartmouth, Massachusetts, 02747
GSK Investigational Site
Northfield, New Jersey, 08225
GSK Investigational Site
Paducah, Kentucky, 42001
GSK Investigational Site
Palm Desert, California, 92260
GSK Investigational Site
Philadelphia, Pennsylvania, 19104
GSK Investigational Site
Philadelphia, Pennsylvania, 19107
GSK Investigational Site
Phoenix, Arizona, 85014
GSK Investigational Site
Phoenix, Arizona, 85020
GSK Investigational Site
Prairie Village, Kansas, 66208
GSK Investigational Site
Salt Lake City, Utah, 84132
GSK Investigational Site
San Francisco, California, 94143
GSK Investigational Site
Silverdale, Washington, 98383
GSK Investigational Site
Stuart, Florida, 34994
GSK Investigational Site
Tampa, Florida, 33612
GSK Investigational Site
Toms River, New Jersey, 08755
GSK Investigational Site
Torrance, California, 90503
GSK Investigational Site
West Mifflin, Pennsylvania, 15122

Other trials in United States

Canada1 site

GSK Investigational Site
Mississauga, Ontario, L4W 1W9

Other trials in Canada

About this study

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)

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.

Read the 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.

Conditions: Atrophy, Geographic
Being tested: GSK933776, Placebo
Keywords: age-related macular degeneration, geographic atrophy, dry AMD
Medical subject headings: Geographic Atrophy, Macular Degeneration

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK933776Drug
GSK933776
PlaceboDrug
Placebo

Study groups in NCT01342926
Study group	Role	What they receive
GSK933776 3 mg/kg	Experimental	3 mg/kg administration of GSK933776 via intravenous infusion Receives: Drug: GSK933776
GSK933776 6 mg/kg	Experimental	6 mg/kg administration of GSK933776 via intravenous infusion Receives: Drug: GSK933776
Placebo	Placebo comparator	Placebo via intravenous infusion Receives: Drug: Placebo
GSK933776 15 mg/kg	Experimental	15 mg/kg administration of GSK933776 via intravenous infusion Receives: Drug: GSK933776

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: Up to 21 months
Number of Participants With Ocular or Non-ocular Serious Adverse Events (SAEs) During the Treatment Period
Measured: 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)
Vital signs included SBP and DBP of Potential Clinical Importance (PCI) at the indicated time points: 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 in sitting position. 'General' is an assessment time not relative to dosing. SBP was defined as: low: <85 millimeter of mercury (mmHg) and high: >160 mmHg and DBP was defined as: low:<45 mmHg and high: >100 mmHg. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Only categories with at least one PCI value are presented.
Measured: Up to 21 months
Number of Participants With Vital Signs of Potential Clinical Importance (PCI) During the Treatment Period: Heart Rate (HR)
Vital signs included HR of CCR at the indicated time points: 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 in sitting position. 'General' is an assessment time not relative to dosing. HR was defined as: low:< 40 beats per minute (bpm) and high: >100 bpm. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Only categories with at least one PCI value are presented.
Measured: 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
Number of Participants With 12-lead Electrocardiogram (ECG) of Potential Clinical Importance (PCI)
12-lead ECG was obtained after 10 minutes rest in a supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF). Abnormal-clinically significant (CS) ECG measurements are presented at indicated time points: Baseline, Month 6, Month 12, Month 18, early withdrawal and at follow-up visit. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measured: Baseline, Month 6, Month 12, Month 18, early withdrawal and at follow-up visit
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.
Measured: At any point from Baseline through follow-up visit.
Number of Participants With Abnormal Magnetic Resonance Imaging (MRI)
Magnetic Resonance Imaging (MRI) was used as a safety assessment to monitor for amyloid related imaging abnormalities (ARIA) events in the brain. MRIs were performed at Baseline and before dose 2, before dose 3, before dose 4, before dose 6, before dose 12, before dose 18 and at follow-up. ARIA-edema/effusions (ARIA-E) and ARIA hemosiderin deposition (ARIA-H) events at any visit are reported.
Measured: Month 2, Month 3, Month 4, Month 6, Month 12, Month 18 and at early withdrawal

Secondary outcomes (10)

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).
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
Maximum Observed Plasma Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) of GSK933776 in Geographic Atrophy Participants
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
Measured: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
Clearance (CL) of GSK933776 in Geographic Atrophy Participants
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.
Measured: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
Estimation of Terminal Phase Half-life (T1/2) of GSK933776 in Geographic Atrophy Participants
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.
Measured: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
Volume of Distribution at Steady-state (Vdss) of GSK933776 in Geographic Atrophy Participants Estimated From Population PK Modeling
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.
Measured: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
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)
Blood samples were collected at the indicated time points on Baseline, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15 and Month 18. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Measured: Baseline, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15 and Month 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jun 20111 Apr 2016

First posted27 Apr 2011 (estimated)
Study start1 Jun 2011
Primary completion1 Apr 2016
Study completion1 Apr 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Atrophy, GeographicStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 191 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01342926
Sponsor's protocol ID: 114341
Status last verified: Mar 2017
First submitted: 26 Apr 2011
Last updated: 5 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
Phase 1/2 Study of VOY-101 in Patients With Advanced Non-Neovascular Age-Related Macular Degeneration
Age-Related Macular Degeneration, Geographic Atrophy
RecruitingPhase 1/2
Autologous Transplantation of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Geographic Atrophy Associated With Age-Related Macular Degeneration
Dry Age-Related Macular Degeneration, Geographic Atrophy
RecruitingPhase 3
A Study Investigating Subcutaneously Administered Pozelimab in Combination With Cemdisiran or Cemdisiran Alone in Adult Participants With Geographic Atrophy
Age-related Macular Degeneration (AMD), Geographic Atrophy (GA)
RecruitingPhase 1
Phase 1 Study of C.001 in Retinal Degeneration
Geographic Atrophy, Stargardt Disease
RecruitingPhase 2/3
A Long-term Extension Study of JNJ-81201887 (AAVCAGsCD59) Parent Studies in Participants With Geographic Atrophy (GA) Secondary to Age-related Macular Degeneration (AMD)
Geographic Atrophy, Macular Degeneration

All Atrophy, Geographic trials

Study at a glance

From the registry record, last updated by the sponsor on 5 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT01342926
Acronym / sponsor ID: 114341
Conditions: Atrophy, Geographic
Keywords: age-related macular degeneration, geographic atrophy, dry AMD
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 191 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 1 Jun 2011
Primary completion: 1 Apr 2016 (actual)
Study completion: 1 Apr 2016 (actual)
First posted: 27 Apr 2011 (estimated)
Results: Posted 5 May 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
GSK933776 3 mg/kg	Experimental	Drug: GSK9337763 mg/kg administration of GSK933776 via intravenous infusion
GSK933776 6 mg/kg	Experimental	Drug: GSK9337766 mg/kg administration of GSK933776 via intravenous infusion
Placebo	Placebo comparator	Drug: PlaceboPlacebo via intravenous infusion
GSK933776 15 mg/kg	Experimental	Drug: GSK93377615 mg/kg administration of GSK933776 via intravenous infusion

Who may qualify

Ages: 55 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (10 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK933776GSK933776	Drug	GSK933776 15 mg/kg, GSK933776 3 mg/kg, GSK933776 6 mg/kg
PlaceboPlacebo	Drug	Placebo

Primary outcome

Change From Baseline in the Area of Geographic Atrophy (GA) Assessed by Color Fundus Photographs (FP) in the Study Eye
Time frame: Baseline (BL), 6 months, 12 months and 18 months
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.
Number of Participants With Ocular or Non-ocular Adverse Events (AEs) During the Treatment Period
Time frame: Up to 21 months
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.
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)
Time frame: Up to 21 months
Vital signs included SBP and DBP of Potential Clinical Importance (PCI) at the indicated time points: 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 in sitting position. 'General' is an assessment time not relative to dosing. SBP was defined as: low: <85 millimeter of mercury (mmHg) and high: >160 mmHg and DBP was defined as: low:<45 mmHg and high: >100 mmHg. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Only categories with at least one PCI value are presented.
Number of Participants With Vital Signs of Potential Clinical Importance (PCI) During the Treatment Period: Heart Rate (HR)
Time frame: 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
Vital signs included HR of CCR at the indicated time points: 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 in sitting position. 'General' is an assessment time not relative to dosing. HR was defined as: low:< 40 beats per minute (bpm) and high: >100 bpm. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Only categories with at least one PCI value are presented.
Number of Participants With 12-lead Electrocardiogram (ECG) of Potential Clinical Importance (PCI)
Time frame: Baseline, Month 6, Month 12, Month 18, early withdrawal and at follow-up visit
12-lead ECG was obtained after 10 minutes rest in a supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF). Abnormal-clinically significant (CS) ECG measurements are presented at indicated time points: Baseline, Month 6, Month 12, Month 18, early withdrawal and at follow-up visit. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
Number of Participants With Abnormal Laboratory Parameter Values of Potential Clinical Importance (PCI)
Time frame: At any point from Baseline through follow-up visit.
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.
Number of Participants With Abnormal Magnetic Resonance Imaging (MRI)
Time frame: Month 2, Month 3, Month 4, Month 6, Month 12, Month 18 and at early withdrawal
Magnetic Resonance Imaging (MRI) was used as a safety assessment to monitor for amyloid related imaging abnormalities (ARIA) events in the brain. MRIs were performed at Baseline and before dose 2, before dose 3, before dose 4, before dose 6, before dose 12, before dose 18 and at follow-up. ARIA-edema/effusions (ARIA-E) and ARIA hemosiderin deposition (ARIA-H) events at any visit are reported.

10 secondary outcomes

Change From Baseline in Area of GA Assessed by Fundus Autofluorescence Images (hypoAF) Corresponding to GA in Study Eye
Time frame: Baseline, 6 months, 12 months and 18 months
Change From Baseline in Area of Total hypoAF in Study Eye
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
Time frame: Month 12 and Month 18
Mean Change in ETDRS-BCVA Score From Baseline at Every Month up to Month 18
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
Time frame: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
Maximum Observed Plasma Concentration (Cmax) and Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ctau) of GSK933776 in Geographic Atrophy Participants
Time frame: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
Clearance (CL) of GSK933776 in Geographic Atrophy Participants
Time frame: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
Estimation of Terminal Phase Half-life (T1/2) of GSK933776 in Geographic Atrophy Participants
Time frame: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
Volume of Distribution at Steady-state (Vdss) of GSK933776 in Geographic Atrophy Participants Estimated From Population PK Modeling
Time frame: Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476
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)
Time frame: Baseline, Month 3, Month 4, Month 5, Month 6, Month 9, Month 12, Month 15 and Month 18

Results and safety

Results posted to the registry on 5 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	46	37
GSK933776 (3 mg/kg)	46	31
GSK933776 (6 mg/kg)	48	34
GSK933776 (15 mg/kg)	51	39

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

Time frame: Baseline (BL), 6 months, 12 months and 18 months. Mean (90% Confidence Interval). Unit: square millimeter (m^2)

Measure	Placebo n = 34	GSK933776 (3 mg/kg) n = 30	GSK933776 (6 mg/kg) n = 35	GSK933776 (15 mg/kg) n = 40
Screening, n=34, 30, 35, 40	-0.52 (-0.86 to -0.17)	-0.94 (-1.30 to -0.57)	-0.99 (-1.33 to -0.65)	-0.96 (-1.28 to -0.64)
6 months, n=34, 30, 35, 39	0.95 (0.61 to 1.30)	0.88 (0.51 to 1.25)	0.73 (0.38 to 1.07)	0.77 (0.44 to 1.09)
12 months, n=33, 29, 34, 40	1.60 (1.26 to 1.95)	1.81 (1.43 to 2.18)	1.83 (1.49 to 2.18)	1.89 (1.57 to 2.21)
18 months, n=34, 30, 32, 39	2.60 (2.25 to 2.95)	2.77 (2.40 to 3.14)	2.88 (2.53 to 3.23)	2.99 (2.67 to 3.31)

Placebo vs GSK933776 (3 mg/kg): Mean Difference (Final Values): -0.07 (90% CI -0.57 to 0.43)
Placebo vs GSK933776 (3 mg/kg): Median Difference (Final Values): 0.20 (90% CI -0.31 to 0.71)
Placebo vs GSK933776 (3 mg/kg): Mean Difference (Final Values): 0.17 (90% CI -0.33 to 0.68)

Population analysed: Efficacy Population. Participants who developed CNV in the study eye during the treatment period are excluded from Efficacy Population per protocol.

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

Time frame: Up to 21 months. Number. Unit: Participants

Measure	Placebo n = 46	GSK933776 (3 mg/kg) n = 46	GSK933776 (6 mg/kg) n = 48	GSK933776 (15 mg/kg) n = 51
Non-ocular AEs	41	42	44	47
Ocular AEs	12	17	15	20

Population analysed: ITT Population: all participants that completed the observation period and Baseline visit, and were subsequently randomized to treatment and were administered at least one IV dose.

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

Time frame: Up to 21 months. Number. Unit: Participants

Measure	Placebo n = 46	GSK933776 (3 mg/kg) n = 46	GSK933776 (6 mg/kg) n = 48	GSK933776 (15 mg/kg) n = 51
Non-ocular SAEs	8	11	9	12
Ocular SAEs	1	0	0	0

Population analysed: ITT Population

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

Time frame: Up to 21 months. Number. Unit: Participants

Measure	Placebo n = 46	GSK933776 (3 mg/kg) n = 46	GSK933776 (6 mg/kg) n = 48	GSK933776 (15 mg/kg) n = 51
SBP Baseline General: > CCR, n=46, 46, 48, 51	1	3	2	5
SBP Baseline General 2:> CCR, n=46, 46, 48, 50	1	2	2	4
SBP Baseline General 3:> CCR, n=45, 46, 48, 50	1	2	2	4
SBP Month 0, Pre-dose:> CCR, n=46, 46, 48, 51	2	1	1	1
SBP Month 0, 0 H:> CCR, n=46, 46, 48, 51	1	1	2	3
SBP Month 1, Pre-dose:> CCR, n=44, 44, 44, 51	2	5	1	2
SBP Month 1, 0 H:> CCR, n=43, 44, 44, 51	3	2	1	2
SBP Month 2, Pre-dose:> CCR, n=44, 43, 42, 49	1	2	3	2

Population analysed: ITT Population

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication up to approximately 21 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	9 of 46 (19.6%)	31 of 46 (67.4%)	Not reported
GSK933776 (3 mg/kg)	11 of 46 (23.9%)	37 of 46 (80.4%)	Not reported
GSK933776 (6 mg/kg)	9 of 48 (18.8%)	32 of 48 (66.7%)	Not reported
GSK933776 (15 mg/kg)	12 of 51 (23.5%)	37 of 51 (72.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

41 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GSK933776 in people with Atrophy, Geographic, run by GlaxoSmithKline at 41 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in the Area of Geographic Atrophy (GA) Assessed by Color Fundus Photographs (FP) in the Study Eye (time frame: Baseline (BL), 6 months, 12 months and 18 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01342926.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2017.