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Predictors of Treatment Response to Aflibercept and Aqueous Cytokine Levels in Patients With Persistent Diabetic Macular Edema Following Treatment With Ranibizumab: An Interventional Prospective Study

Primary Purpose

Diabetic Macular Edema

Status

Unknown status

Phase

Phase 4

Locations

Study Type

Interventional

Intervention

aflibercept

About this trial

This is an interventional treatment trial for Diabetic Macular Edema focused on measuring Diabetic Macular Edema, Ocular Cytokines, aflibercept, ranibizumab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria

Male or female aged 18 years or above
Presence of Non Proliferative Diabetic Retinopathy (NPDR)
Prior treatment with ≥ 6 intravitreal ranibizumab injections but no treatment in the last 4 weeks and less than 10% improvement in Central Macular Thickness on OCT scan and less than 1 line improvement in vision from baseline and less than 10% reduction in macular volume with Snellan Acuity 20/40 to 20/400
Patients with DME with central macular thickness of 310μm or more on SD-OCT (cirrus)
Subjects with Type I or II diabetes mellitis
Willing and able to provide informed consent for participation in the study

Exclusion Criteria

Proliferative diabetic retinopathy in the study eye or PRP within the last 12 months or anticipated PRP in the next 6 months
Uncontrolled glaucoma
History of intraocular surgery within 3 months in the study eye
History of vitrectomy surgery
Laser treatment within 3 months of study eye
Vitreomacular traction, epiretinal membrane or any other maculopathy in the study eye
Prior intravitreal injection within the past 6 months
Known allergy to the study drug or fluorescein
History of stroke or AMI within 6 months of enrolment
Patients receiving dialysis for renal failure
Patients currently on systemic immunosuppression
Patients on two or more class of medication for glaucoma in study eye
Patients with tuberculosis
Patients who are pregnant.
Unwilling or unable to follow or comply with all study related procedures

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

aflibercept

Arm Description

aflibercept treatment aflibercept, 40 mg/mL Solution for Intravitreal Injection

Outcomes

Primary Outcome Measures

Change in cytokine levels (picograms per mL) in patients with DME who were previously non-responders to ranibizumab (non-responders) between baseline aflibercept injection.

Secondary Outcome Measures

Relation of baseline aqueous cytokine levels in patients with DME who were previously non-responders to ranibizumab (non-responders) to baseline Snellen BCVA in response to aflibercept

Full Information

NCT ID

NCT02651168

First Posted

January 7, 2016

Last Updated

January 7, 2016

Sponsor

Unity Health Toronto

1. Study Identification

Unique Protocol Identification Number

NCT02651168

Brief Title

Predictors of Treatment Response to Aflibercept and Aqueous Cytokine Levels in Patients With Persistent Diabetic Macular Edema Following Treatment With Ranibizumab: An Interventional Prospective Study

Official Title

Study Type

Interventional

2. Study Status

Record Verification Date

January 2016

Overall Recruitment Status

Unknown status

Study Start Date

March 2016 (undefined)

Primary Completion Date

March 2018 (Anticipated)

Study Completion Date

June 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Unity Health Toronto

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

Diabetic macular edema refers to swelling (fluid accumulation) in the center of the retina. The retina is like the film of a camera and is located in the back of the eye. This condition can develop in diabetics where swelling results from leaking of fluid from the blood vessels of the eye, into the center of the retina, the macula. If left untreated, this can affect central. The current standard treatment for diabetic macular edema includes medications injected directly into the eye (intravitreal injections) and laser eye treatment. The drugs that are injected directly into the eye are known as anti-VEGF agents which help to reduce the leaking. This includes bevacizumab (Avastin®) and ranibizumab (Lucentis®). However, some patients do not respond well to these anti-VEGF treatments and will be given the option of switching to an another newer anti-VEGF medication, called aflibercept (Eylea®) that is approved to treat DME. A recent large study has demonstrated that aflibercept was as efficacious as other anti-VEGF therapies listed above and was even superior in patients with worse vision (Diabetic Retinopathy Clinical Research Network, Wells JA, Glassman AR, et al. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema. N Engl J Med. 2015:150218140025008-150218140025008). The purpose of this study is to determine what factors affect the treatment response to aflibercept (amount of swelling reduction) for patients with diabetic macular edema, who were previously unresponsive to ranibizumab injections.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Macular Edema

Keywords

Diabetic Macular Edema, Ocular Cytokines, aflibercept, ranibizumab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

aflibercept

Arm Type

Other

Arm Description

aflibercept treatment aflibercept, 40 mg/mL Solution for Intravitreal Injection

Intervention Type

Biological

Intervention Name(s)

aflibercept

Other Intervention Name(s)

Eylea

Intervention Description

EYLEA (aflibercept, solution for intravitreal injection) is a recombinant fusion protein consisting of portions of human Vascular Endothelial Growth Factor (VEGF) receptor 1 and 2 extracellular domains fused to the Fc portion of human IgG1 and formulated as an iso-osmotic solution for intravitreal administration. Aflibercept is produced in Chinese hamster ovary (CHO) K1 cells by recombinant DNA technology.

Primary Outcome Measure Information:

Title

Change in cytokine levels (picograms per mL) in patients with DME who were previously non-responders to ranibizumab (non-responders) between baseline aflibercept injection.

Time Frame

1month, 2 months, 3 months

Secondary Outcome Measure Information:

Title

Relation of baseline aqueous cytokine levels in patients with DME who were previously non-responders to ranibizumab (non-responders) to baseline Snellen BCVA in response to aflibercept

Time Frame

3 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria Male or female aged 18 years or above Presence of Non Proliferative Diabetic Retinopathy (NPDR) Prior treatment with ≥ 6 intravitreal ranibizumab injections but no treatment in the last 4 weeks and less than 10% improvement in Central Macular Thickness on OCT scan and less than 1 line improvement in vision from baseline and less than 10% reduction in macular volume with Snellan Acuity 20/40 to 20/400 Patients with DME with central macular thickness of 310μm or more on SD-OCT (cirrus) Subjects with Type I or II diabetes mellitis Willing and able to provide informed consent for participation in the study Exclusion Criteria Proliferative diabetic retinopathy in the study eye or PRP within the last 12 months or anticipated PRP in the next 6 months Uncontrolled glaucoma History of intraocular surgery within 3 months in the study eye History of vitrectomy surgery Laser treatment within 3 months of study eye Vitreomacular traction, epiretinal membrane or any other maculopathy in the study eye Prior intravitreal injection within the past 6 months Known allergy to the study drug or fluorescein History of stroke or AMI within 6 months of enrolment Patients receiving dialysis for renal failure Patients currently on systemic immunosuppression Patients on two or more class of medication for glaucoma in study eye Patients with tuberculosis Patients who are pregnant. Unwilling or unable to follow or comply with all study related procedures

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Rajeev Muni, MD

Phone

4168677411

First Name & Middle Initial & Last Name or Official Title & Degree

Phillip To

Phone

4168677411

top@smh.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rajeev Muni, MD

Organizational Affiliation

St. Michael's Hospital Eye Clinic, Toronto, Ontario, Canada, M5C2T2

Official's Role

Principal Investigator

12. IPD Sharing Statement

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