PRedictive Factors and Changes From Treatment in iPCV Versus CSR Versus nAMD With afLibercept (PRaCTICAL)

PRedictive Factors and Changes From Treatment in Idiopathic Polypoidal Choroidal Vasuclopathy Versus Central Serous Chorioretinopathy Versus Neovascular Age Related Macular Degeneration With afLibercept

The presence of PEDs in nAMD, CSR and iPCV can present a diagnostic challenge in the elderly population; despite detailed diagnostic testing to differentiate these three conditions, misdiagnosis and mistreatment still occurs. One potential way of differentiating these three conditions might be to compare cytokine profiles in nAMD versus CSR versus iPCV. This information may be useful in creating a diagnostic aqueous cytokine and hormone profile to differentiate between nAMD, CSR and iPCV.

The primary goal of this study is to compare baseline aqueous cytokine and cortisol levels between nAMD, CSR, and iPCV patients and age-matched cataract controls. The secondary objective is to assess intra-group changes in visual and anatomical outcomes in nAMD, CSR and iPCV patients with PED treated with aflibercept and correlate these changes to baseline cytokines.

Study Overview

• Status: Unknown
• Conditions: Age Related Macular Degeneration; Central Serous Chorioretinopathy; Idiopathic Poplypoidal Choroidal Vasculopathy
• Intervention / Treatment: Drug: aflibercept

Detailed Description

The presence of Pigment Epithelial Detachments (PEDs) in neovascular Age-related Macular Degeneration (nAMD), Central serous chorioretinopathy (CSR) and idiopathic Poplypoidal Choroidal Vasculopathy (iPCV) can present a diagnostic challenge in the elderly population; despite detailed diagnostic testing to differentiate these three conditions, misdiagnosis and mistreatment still occurs. One potential way of differentiating these three conditions might be to compare cytokine profiles in nAMD versus CSR versus iPCV. In nAMD, growth factors and cytokines, such as vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF), interleukin 6 (IL-6) and placenta growth factor (PLGF) are known to play an important role in the development of CNV angiogenesis. Aqueous samples from CSR eyes have been analyzed for various growth factors and cytokines, where levels of interlukin (IL)-6, IL-8 and monocyte chemoattractant protein-1 do not differ from healthy controls, and platelet-derived growth factor (PDGF) levels appear to be lower than controls. In addition, there is evidence to demonstrate that CSR is associated with elevated cortisol serum levels. Cortisol has been analyzed in the aqueous humor of glaucoma and cataract patients; however, the presence of cortisol in aqueous humor in CSR patients has not yet been identified. One study comparing iPCV versus controls found elevated levels of IL-23. Cytokines have also been compared between nAMD and iPCV showing elevated levels of CRP and IL-10 in eyes with iPCV or nAMD. However, there have not been any studies yet comparing aqueous cytokine levels, including PLGF between iPCV, CSR, and nAMD patients. This information may be useful in creating a diagnostic aqueous cytokine and hormone profile to differentiate between nAMD, CSR and iPCV.

If left untreated, PEDs associated with nAMD, CSR, and iPCV may lead to the loss of central vision. We propose to compare the effectiveness of aflibercept in the treatment of PEDs associated with nAMD, CSR and iPCV.

The primary goal of this study is to compare baseline aqueous cytokine and cortisol levels between nAMD, CSR, and iPCV participants and age-matched cataract controls. We will not be looking at changes in cytokine levels after treatment. The secondary objective is to assess intra-group changes in visual and anatomical outcomes in nAMD, CSR and iPCV participants with PED treated with aflibercept and correlate these changes to baseline cytokines.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Cindy Rutz; Phone Number: 416-480-5091; Email: cindy.rutz@sunnybrook.ca
• Study Contact Backup: Name: Radha P. Kohly, MD PhD FRCSC; Phone Number: 4164805607; Email: radha.kohly@sunnybrook.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Research Institute
      • Contact: Radha Kohly, MD, PhD, FRCSC; Phone Number: 416-480-5607; Email: radha.kohly@sunnybrook.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria for all study eye groups:

1. 18 years of age or older
2. Ability to provide signed informed consent
3. Capable of complying with study protocol and required diagnostic tests
4. Meets study eye criteria for each respective group (see Section 5 above)
5. Participants in the nAMD, CSR, and iPCV groups must use an acceptable method of birth control during this study and for 6 months following completion of the study. The participants in the control group will not be receiving IP and are not required to meet this inclusion criterion.

Exclusion criteria for all study eye groups:

1. Previous intraocular injections including anti-VEGF therapy or steroid medication, or macular laser for all groups
2. Any co-existing maculopathy or retinopathy in the study eye
3. Participants with a history of either type I or type II diabetes
4. Intraocular surgery in the study eye within the past 4 months
5. Currently on systemic steroid therapy in any form (drops, skin creams, inhalation/intranasal sprays, intravenous) or immunosuppression for the last 3 months
6. Participants on renal dialysis
7. Pregnant and nursing mothers
8. Participants who are hypersensitive to this drug, to any ingredient in the formulation, or to any component of the container.
9. Ocular or periocular infection
10. Active intraocular inflammation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: neovascular AMD group with PED; Patients in this group will be administered aflibercept intravitreal injection 2 mg (0.05 mL), administered at baseline, month 1, and month 2, for a total of 3 injections. Study will end for these patients at month 4, where no injection will be given. A clinical exam and OCT imaging will be performed each visit.	Drug: aflibercept; Therapeutic/Pharmacological Classification: VEGF - Anti-neovascularization agent Route(s) of Administration: Intravitreal Injection Dosage Form: Solution 40 mg/ml Proposed Indication: Treatment of Pigment Epithelial Detachments (PEDs) associated with neovascular Age-related Macular Degeneration (nAMD), Central serous chorioretinopathy (CSR), and idiopathic Poplypoidal Choroidal Vasculopathy (iPCV).; Other Names: Eylea
Experimental: CSR group with PED; Patients in this group will be administered aflibercept intravitreal injection 2 mg (0.05 mL), administered at baseline, month 1, and month 2, for a total of 3 injections. Study will end for these patients at month 4, where no injection will be given. A clinical exam and OCT imaging will be performed each visit.	Drug: aflibercept; Therapeutic/Pharmacological Classification: VEGF - Anti-neovascularization agent Route(s) of Administration: Intravitreal Injection Dosage Form: Solution 40 mg/ml Proposed Indication: Treatment of Pigment Epithelial Detachments (PEDs) associated with neovascular Age-related Macular Degeneration (nAMD), Central serous chorioretinopathy (CSR), and idiopathic Poplypoidal Choroidal Vasculopathy (iPCV).; Other Names: Eylea
Experimental: iPCV group with PED; Patients in this group will be administered aflibercept intravitreal injection 2 mg (0.05 mL), administered at baseline, month 1, and month 2, for a total of 3 injections. Study will end for these patients at month 4, where no injection will be given. A clinical exam and OCT imaging will be performed each visit.	Drug: aflibercept; Therapeutic/Pharmacological Classification: VEGF - Anti-neovascularization agent Route(s) of Administration: Intravitreal Injection Dosage Form: Solution 40 mg/ml Proposed Indication: Treatment of Pigment Epithelial Detachments (PEDs) associated with neovascular Age-related Macular Degeneration (nAMD), Central serous chorioretinopathy (CSR), and idiopathic Poplypoidal Choroidal Vasculopathy (iPCV).; Other Names: Eylea
No Intervention: cataract patients; Patients diagnosed with cataracts requiring cataract surgery will serve as study controls. No intervention will be applied to these patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline aqueous humour cytokine levels in nAMD, CSR, and iPCV patients	The primary outcome is to compare the baseline aqueous inflammatory cytokine levels (pg/ml) and baseline aqueous cortisol levels (pg/ml) through analyzing anterior chamber aqueous fluid in patients with nAMD, CSR, and iPCV patients receiving aflibercept intravitreal injections, and compare with the aquueous fluid of age-matched control patients undergoing cataract surgery.	4 months from baseline intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of the intra-group changes in best-corrected visual acuity using Snellen eye charts after aflibercept treatment in patients with nAMD, CSR, and iPCV for 4 months	To assess the intra-group changes in best-corrected visual acuity using Snellen eye charts after aflibercept treatment in patients with nAMD, CSR, and iPCV for 4 months	4 months from baseline intervention
Assessment of the intra-group changes in anatomical changes via OCT imaging from baseline after aflibercept treatment in patients with nAMD, CSR, and iPCV for 4 months	To assess the intra-group changes in anatomical changes via OCT imaging from baseline after aflibercept treatment in patients with nAMD, CSR, and iPCV for 4 months	4 months from baseline intervention

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Investigators: Principal Investigator: Radha P. Kohly, MD PhD FRCSC, Sunnybrook Health Sciences Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2018
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: February 12, 2015
• First Submitted That Met QC Criteria: February 11, 2016
• First Posted (Estimate): February 12, 2016

Study Record Updates

• Last Update Posted (Actual): January 28, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: aflibercept
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Central Serous Chorioretinopathy; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: PRaCTICAL 100-17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No