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

NCT ID: NCT02681783

Last Updated: 2021-01-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-01
• Study Completion Date: 2022-12-01

Brief Summary

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.

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.

Conditions

Central Serous Chorioretinopathy; Age Related Macular Degeneration; Idiopathic Poplypoidal Choroidal Vasculopathy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

aflibercept

Intervention Type: DRUG

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).

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.

Group Type: EXPERIMENTAL

aflibercept

Intervention Type: DRUG

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).

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.

Group Type: EXPERIMENTAL

aflibercept

Intervention Type: DRUG

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).

cataract patients

Patients diagnosed with cataracts requiring cataract surgery will serve as study controls. No intervention will be applied to these patients.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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).

Intervention Type: DRUG

Other Intervention Names

Eylea

Eligibility Criteria

Inclusion Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role: lead

Responsible Party

Dr. Radha Kohly

Assistant Professor, University of Toronto

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Radha P. Kohly, MD PhD FRCSC

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Center

Locations

Sunnybrook Research Institute

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Radha P. Kohly, MD PhD FRCSC

Role: CONTACT

radha.kohly@sunnybrook.ca

4164805607

Cindy Rutz

Role: CONTACT

cindy.rutz@sunnybrook.ca

416-480-5091

Facility Contacts

Radha Kohly, MD, PhD, FRCSC

Role: primary

radha.kohly@sunnybrook.ca

416-480-5607

Other Identifiers

PRaCTICAL 100-17

Identifier Type: -

Identifier Source: org_study_id