Evaluation of Wet Age-Related Macular Degeneration (AMD) Genetic Profile Interactions With Ranibizumab Treatment Outcomes

NCT01363570 | Completed

• 1 other identifier: AMDgene12011
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

Age Related Macular Degeneration (AMD) is the leading cause of blindness in North America. This condition causes a progressive loss of central vision, the part of your vision that allows you to read, drive and see images in sharp detail directly in front of you. The wet form of AMD is characterized by the growth and leakage of small blood vessels into the choroid layer of the eye, or the back of the eye. These leaking blood vessels disrupt the structure and function of the eye, causing loss of vision, particularly the sharp vision created by the macula area of the eye. Currently, the best treatment for wet AMD is a series of injections of an anti-vascular endothelial growth factor (anti-VEGF) drug, ranibizumab (Lucentis). The clinical response to treatment is varied. Approximately 70% of patients see a moderate vision gain (3-line gain on a visual acuity chart), but there are 30% who do not see a similar improvement in vision. There is no way to identify those patients who will respond with significant vision gain versus those who will not experience moderate vision gain. Recent research into AMD has demonstrated that genetic mutations are proving to be key risk factors for patients developing wet AMD, with up to 80% of wet AMD cases explained by inherited genetic variations. Scientists have theorized that there may be a genetic difference between those patients who see significant responses to treatment and those who do not. The investigators will be testing participant's genetic profile using the Macula Risk test and following their progress through the standard treatment for wet AMD over the course of this study. This study aims to demonstrate the association between known genetic variations and patient responses to treatment.

Conditions

Age Related Macular Degeneration

Keywords

Macular Degeneration; Age related macular degeneration; Macula Risk; Genetic test; Anti-inflammatory; Anti-vascular endothelial growth factor (Anti-VEGF); Lucentis; Ranibizumab; Vision loss

Outcome Measures

Primary Outcomes (1)

• Gains in visual acuity

  Percent probability gains in visual acuity will be assessed by comparing best corrected visual acuity at each follow up appointment by the standardized vision testing, early treatment diabetic retinopathy study (ETDRS) test. The ETDRS visual acuity test was first developed to effectively evaluate visual changes following panretinal photocoagulation in patients with diabetic retinopathy. This method of measuring visual acuity was more accurate than previous methods, and thus has become the global standard, especially for clinical trials where it is essential to have utmost accuracy.

  Baseline and months 1, 2, 3, 4, 5, and 6

Secondary Outcomes (6)

• Changes in choroid vessel activity in lesion growth and activity at choroid

  Baseline and months 1, 2, 3, 4, 5 and 6

• Rate of cataract progression

  Baseline and months 1, 2, 3, 4, 5, and 6

• Resolution of macular edema

  Baseline and months 1, 2, 3, 4, 5, 6

• Mean change in visual acuity according to identified genetic mutations

  Baseline and Months 1, 2, 3, 4, 5, 6

• Mean change in visual acuity regardless of genetic profile results

  Baseline and Months 1, 2, 3, 4, 5, 6

Study Arms (1)

Ranibizumab

OTHER

Ranibizumab is the current gold standard treatment for wet age-related macular degeneration. This intervention is approved by Health Canada, covered by OHIP (Ontario Health Insurance Plan) and used regularly by ophthalmologists in Canada. Participants will receive intravitreal injections of ranibizumab each month for up to 6 months, with ocular testing at each appointment as prescribed by the study protocol.

Drug: Ranibizumab

Interventions

Ranibizumab DRUG

Intra-vitreal injections of 0.5mg/0.05 mL dosage, injected at months 0, 1, and 2. For those requiring additional injections, patients will receive monthly treatment up to a maximum of 6 months total.

Also known as: Lucentis

Ranibizumab

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be at least 18 years of age
• Choroidal neovascularization (CNV) secondary to age-related macular degeneration
• CNV under geometric center of the foveal avascular zone
• Evidence of activity on fundus fluorescein angiography
• Evidence of CNV activity as suggested by one of the following: sub-retinal hemorrhage, sub-retinal lipid, documented loss of 3 lines of vision within the last 3 months
• Visual acuity of between 20/40 and 20/300 in the study eye tested via Early treatment of Diabetic Retinopathy Study (ETDRS) eye chart score of 34 to 73 letters at 2 meters.

You may not qualify if:

• Individuals with choroidal neovascularization from causes other than AMD
• Patients physically unable to tolerate intravenous fluorescein angiography
• Patients with medically uncontrolled glaucoma
• Any intraocular surgery within 3 months in the study eye
• Prior retinal or vitreous surgery including vitrectomy or scleral buckling
• Any significant ocular disease other than AMD that has compromised or could compromise vision in the study eye and confound analysis of the primary outcome
• Individuals with physical or mental disabilities that prevent accurate vision testing
• History of any laser treatment of CNV in study eye (laser photocoagulation or prior photodynamic therapy), or anti-VEGF (ranibizumab or bevacizumab) in the past 6 months in the study eye.

Sponsors & Collaborators

• McMaster University: lead
• Canadian National Institute for the Blind: collaborator

Study Sites (2)

St. Joseph's Healthcare Hamilton Regional Eye Centre

Hamilton, Ontario, L8G 5E4, Canada

Location

Toronto Western Hospital Eye Clinic

Toronto, Ontario, M5T 2S8, Canada

Location

MeSH Terms

Conditions

Macular Degeneration; Vision Disorders

Interventions

Ranibizumab

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Varun Chaudhary, MD, FRCSC

  St. Joseph's Healthcare Hamilton/McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2011
• First Posted: June 1, 2011
• Study Start: January 1, 2012
• Primary Completion: October 1, 2014
• Study Completion: October 1, 2014
• Last Updated: March 17, 2016

Record last verified: 2016-03

Locations

CA (2)