Genetic Analysis of Patients Responsive to Ranibizumab But Resistant to Aflibercept

Age-Related Macular Degeneration Clinical Trial

Official title:

Genetic Analysis of Patients With Neovascular Age-Related Macular Degeneration Responsive to Ranibizumab But Resistant to Aflibercept

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02291887
• Other study ID #: ARCMichigan
• Status: Completed
• Phase: N/A
• First received: November 12, 2014
• Last updated: November 15, 2017
• Start date: December 22, 2014
• Est. completion date: July 1, 2015

Study information

• Verified date: November 2017
• Source: Associated Retinal Consultants, Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

A cohort of patients responsive to treatment with ranibizumab but resistant to

aflibercept were identified in a previously conducted retrospective study. Identified

patients will have their blood drawn for genome wide sequencing. The sequencing

data will be compiled and analyzed in an attempt to identify a common genetic basis

for patients susceptible to ranibizumab but resistant to aflibercept.

Description:

A cohort of patients responsive to treatment with ranibizumab but resistant to

aflibercept were identified in a previously conducted retrospective study. Identified

patients will have their blood drawn for genome wide sequencing. The sequencing

data will be compiled and analyzed in an attempt to identify a common genetic basis

for patients susceptible to ranibizumab but resistant to aflibercept.

Blood samples will be drawn for genetic analysis for all patients enrolled in the study.

The sample (1 tube- 6mL of blood) will be collected using - 8.5mL PAXgene Blood DNA

Tubes (http://www.qiagen.com/products/catalog/sample-technologies/dna-sample-

technologies/genomic-dna/paxgene-blood-dna-tubes).

Samples will be stored at -80 until time for analysis. Note that some blood draws will be performed at

satellite clinics and transported to main facility for storage in -80 freezer. It is the understanding of

ARC PI and staff that the PAXgene Blood DNA Tubes keep samples stable at room temp for 1-2

days.

However, staff will transport samples in timely fashion (room temp, on ice, dry ice,

etc), to -80 freezer for storage until all samples are collected. Once all samples are

collected, they will be shipped to Genentech for analysis. DNA extraction, the generation of genetic

data, and subsequent analysis will be performed at Genentech or via third party. DNA will be assayed

for polymorphisms through genome wide SNP chip or whole genome sequencing. The subject's

genotype or haplotype will be correlated with their visual response and OCT response.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: July 1, 2015
• Est. primary completion date: July 1, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Subjects will be eligible if the following criteria are met:

• Demonstrate worsening of exudation when switched from ranibizumab to aflibercept

• Ability to provide written informed consent and comply with study assessments for the full duration of the study

Exclusion Criteria:

• Any other condition that the investigator believes would pose a significant hazard to the subject

Related Conditions & MeSH terms

• Age-Related Macular Degeneration
• Macular Degeneration

Intervention

Drug:
• Ranibizumab
Intravitreal injection of Ranibizumab
• Aflibercept
Intravitreal injection of Aflibercept

Locations

Country	Name	City	State
United States	Associated Retinal Consultants	Royal Oak	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Associated Retinal Consultants, Michigan	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (7)

D'Amico DJ. Diseases of the retina. N Engl J Med. 1994 Jul 14;331(2):95-106. Review. — View Citation

Eyetech Study Group. Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Ophthalmology. 2003 May;110(5):979-86. — View Citation

Feigl B, Brown B, Lovie-Kitchin J, Lee L. Dynamics of retinal function after multiple photodynamic therapies in age-related macular degeneration: a report of cases. Doc Ophthalmol. 2005 Nov;111(3):135-48. Epub 2006 Mar 6. — View Citation

Heier JS, Antoszyk AN, Pavan PR, Leff SR, Rosenfeld PJ, Ciulla TA, Dreyer RF, Gentile RC, Sy JP, Hantsbarger G, Shams N. Ranibizumab for treatment of neovascular age-related macular degeneration: a phase I/II multicenter, controlled, multidose study. Opht — View Citation

Michels S, Schmidt-Erfurth U, Rosenfeld PJ. Promising new treatments for neovascular age-related macular degeneration. Expert Opin Investig Drugs. 2006 Jul;15(7):779-93. Review. — View Citation

Rosenfeld PJ, Heier JS, Hantsbarger G, Shams N. Tolerability and efficacy of multiple escalating doses of ranibizumab (Lucentis) for neovascular age-related macular degeneration. Ophthalmology. 2006 Apr;113(4):623.e1. — View Citation

Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: Phase III clinical trial results. Ophthalmol Clin North Am. 2006 Sep;19(3):361-72. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genetic characteristics of patients responsive to Ranibizumab but Resistant to Aflibercept	To determine a genetic basis for patients responsive to ranibizumab but resistant to aflibercept.	1 day