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

NCT01342926 | Completed Phase 2 Results DMC

• 1 other identifier: 114341
• Study Type: interventional
• Target: 191
• Locations: 2 countries
• Sites: 41

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.

Conditions

Atrophy, Geographic

Keywords

age-related macular degeneration; geographic atrophy; dry AMD

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  Up to 21 months

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

  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.

  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.

  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).

  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.

  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.

  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

  Baseline, 6 months, 12 months and 18 months

• Change From Baseline in Area of Total hypoAF in Study Eye

  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

  Month 12 and Month 18

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

  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

  Day 56, Day 63, 70 or 77, Day 84, Day 112, Day 140, Day 224, Day 308, Day 392 and Day 476

Study Arms (4)

GSK933776 3 mg/kg

EXPERIMENTAL

3 mg/kg administration of GSK933776 via intravenous infusion

Drug: GSK933776

GSK933776 6 mg/kg

EXPERIMENTAL

6 mg/kg administration of GSK933776 via intravenous infusion

Drug: GSK933776

Placebo

PLACEBO COMPARATOR

Placebo via intravenous infusion

Drug: Placebo

GSK933776 15 mg/kg

EXPERIMENTAL

15 mg/kg administration of GSK933776 via intravenous infusion

Drug: GSK933776

Interventions

GSK933776 DRUG

GSK933776

GSK933776 15 mg/kg; GSK933776 3 mg/kg; GSK933776 6 mg/kg

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (41)

GSK Investigational Site

Phoenix, Arizona, 85014, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85020, United States

Location

GSK Investigational Site

Arcadia, California, 91007, United States

Location

GSK Investigational Site

Irvine, California, 92697, United States

Location

GSK Investigational Site

La Jolla, California, 92037, United States

Location

GSK Investigational Site

Los Angeles, California, 90033-4500, United States

Location

GSK Investigational Site

Palm Desert, California, 92260, United States

Location

GSK Investigational Site

San Francisco, California, 94143, United States

Location

GSK Investigational Site

Torrance, California, 90503, United States

Location

GSK Investigational Site

Golden, Colorado, 80401, United States

Location

GSK Investigational Site

Miami, Florida, 33136, United States

Location

GSK Investigational Site

Stuart, Florida, 34994, United States

Location

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Augusta, Georgia, 30909, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46290, United States

Location

GSK Investigational Site

New Albany, Indiana, 47150, United States

Location

GSK Investigational Site

Leawood, Kansas, 66211, United States

Location

GSK Investigational Site

Prairie Village, Kansas, 66208, United States

Location

GSK Investigational Site

Louisville, Kentucky, 40215, United States

Location

GSK Investigational Site

Paducah, Kentucky, 42001, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21204, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21287, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02111, United States

Location

GSK Investigational Site

North Dartmouth, Massachusetts, 02747, United States

Location

GSK Investigational Site

Detroit, Michigan, 48202, United States

Location

GSK Investigational Site

Northfield, New Jersey, 08225, United States

Location

GSK Investigational Site

Toms River, New Jersey, 08755, United States

Location

GSK Investigational Site

New York, New York, 10003, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

Location

GSK Investigational Site

West Mifflin, Pennsylvania, 15122, United States

Location

GSK Investigational Site

Ladson, South Carolina, 29406, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

Abilene, Texas, 79606, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

GSK Investigational Site

Galveston, Texas, 77550, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Salt Lake City, Utah, 84132, United States

Location

GSK Investigational Site

Charlottesville, Virginia, 22903, United States

Location

GSK Investigational Site

Silverdale, Washington, 98383, United States

Location

GSK Investigational Site

Mississauga, Ontario, L4W 1W9, Canada

Location

MeSH Terms

Conditions

Geographic Atrophy; Macular Degeneration

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2011
• First Posted: April 27, 2011
• Study Start: June 1, 2011
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: May 5, 2017
• Results First Posted: May 5, 2017

Record last verified: 2017-03

Locations

CA (1); US (40)