Finasteride for Chronic Central Serous Chorioretinopathy

Study Overview
=================
Brief Summary
-----------------
Background: Central serous chorioretinopathy (CSC) is a disease that causes fluid to collect under the retina. It affects the macula, which is in the center of the retina and is needed for sharp, clear vision. In many cases, CSC resolves on its own and does not need treatment. However, in some cases it does not go away or comes back after treatment. This is known as chronic CSC. Chronic CSC may be caused by hormones called androgens. Finasteride is a drug that can alter the effects certain of androgens. Researchers want to compare finasteride with a placebo to see if it is a safe and effective treatment for chronic CSC. Objectives: - To see if finasteride is a safe and effective treatment for chronic CSC. Eligibility: - Individuals at least 18 years of age who have chronic CSC in one or both eyes. Design: Participants will be screened with a physical exam and medical history. A full eye exam will be performed. Blood and urine samples will also be collected. Some participants may have photodynamic therapy (PDT), the standard treatment for CSC. PDT helps to reduce the amount of fluid in the eye. Participants will need to wait for 3 months after PDT before starting the finasteride study. Participants will be separated into two groups. One group will take finasteride 5 mg (formulated into capsules); the other group will take a placebo capsule. All participants will take the capsules for 3 months. After 3 months on the assigned capsule (finasteride or placebo), all participants will have the opportunity to take finasteride for at least another 4 years and 9 months. This phase of the study is optional. Participants will have regular study visits. At each visit, they will have physical exams and eye exams. They will also provide blood and urine samples. During the first 3 months, participants will have 2 study visits. After 3 months, if the participant continues in the optional (or as needed) phase of the protocol, visits will occur at Month 6, Month 12 and every 12 months thereafter. However, additional visits may be needed.

Detailed Description
-----------------
Objective: Central serous chorioretinopathy (CSC) is a chorioretinal disorder characterized by an accumulation of serous fluid under the retina. Although acute CSC tends to resolve spontaneously on its own with minimal sequelae, chronic CSC tends to persist and lead to irreversible visual loss. The pathogenesis of CSC is complex. However, systemic androgens have been implicated. Finasteride is an anti-androgen medication that is widely used in the treatment of various conditions. A previous study performed at the NEI demonstrated a reduction in the amount of subretinal fluid among participants treated with 5 mg of finasteride. The objective of this study is to further investigate the efficacy of oral finasteride as a treatment for chronic CSC. Study Population: Thirty-eight participants with chronic CSC are eligible. Up to an additional four participants may be enrolled to account for participants who withdraw from the study prior to Month 3. Design: In this Phase II, single-center, placebo-controlled, double-masked, randomized trial, investigational product will be administered to two different groups. Half of the participants will be randomized to 5 mg oral finasteride for the initial three months. The other half of the participants will be randomized to placebo for the first three months. At the end of three months of treatment, all participants may be followed for at least four years and nine months. During this follow-up period, all participants will be able to receive finasteride therapy pro re nata (PRN) if subretinal fluid re-emerges. The PRN phase will last until the last participant completes the five years of follow-up. Other standard care treatments, such as photodynamic therapy, will also be permitted after the primary outcome at three months. Outcome Measures: The primary outcome for regulatory filing is the proportion of participants with an improvement in best-corrected visual acuity (BCVA) ≥ 15 letters at three months compared to baseline in the study eye. The primary outcome for publication of the study results is the proportion of participants with a subretinal fluid volume decrease ≥ 50% at three months compared to baseline in the study eye. Secondary efficacy outcomes include changes in BCVA, changes in the maximum retinal volume as measured on optical coherence tomography (OCT), changes in central retinal thickness on OCT, changes in leakage as seen on fluorescein angiography (FA), changes in size of existing plaque(s) on indocyanine green (ICG) angiography, changes in autofluorescence patterns seen on fundus autofluorescence (FAF) imaging, changes in mean macular sensitivity as assessed by microperimetry, changes in serum levels of testosterone and dihydrotestosterone (DHT), as well as changes in urine levels of cortisol during the study period. Safety outcomes include the number and severity of adverse reactions from the investigational product and the number of withdrawals.

Official Title
-----------------
Phase II, Randomized, Placebo-Controlled Study for the Evaluation of Finasteride in the Treatment of Chronic Central Serous Chorioretinopathy

Conditions
-----------------
Retinal Disease

Intervention / Treatment
-----------------
* Drug: Finasteride
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Participant must have chronic Central Serous Chorioretinopathy (CSC) in at least one eye as defined by all of the following criteria. This eye will be referred to as the study eye. The presence of subretinal fluid, as determined by optical coherence tomography (OCT), AND The subretinal fluid must have been present for at least three months or recurrent in cases of chronic CSC/diffuse retinal pigment epitheliopathy, AND/OR The presence of characteristic fluorescein angiographic or autofluorescence features of CSC, such as one or more pinpoint leaks and/or diffuse retinal pigment epitheliopathy noted on fluorescein or descending tract lesions on autofluorescence. Participant must have a steady fixation in the study eye. Participant must have media clear enough in the foveal or parafoveal area in the study eye for good quality photographs. Participant must have visual acuity between 20/25 and 20/400 in the study eye. EXCLUSION CRITERIA: Participant has evidence of choroidal neovascularization (CNV) in the study eye. Participant is expected to need ocular surgery in the study eye during the first three months of the study. Participant has had photodynamic therapy (PDT) or focal laser treatment in the study eye within three months prior to enrollment or is expected to need PDT or focal laser treatment in the study eye during the first three months of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Finasteride 5 mg<br>Participants randomly assigned to the finasteride 5 mg arm were instructed to take one capsule daily for three months. | Drug: Finasteride<br>* Finasteride is available as white, round 5 mg tablets. During the masked period, the tablets are re-formulated in capsules with inactive ingredients. The re-formulated finasteride capsules are indistinguishable from the placebo capsules.<br>* Other names: Proscar®;|
| Placebo Comparator: Placebo<br>Participants randomly assigned to the placebo arm will instructed to take one capsule daily for three months. | Drug: Placebo<br>* Capsule with no active ingredients to mimic finasteride<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With an Improvement in Best-corrected Visual Acuity (BCVA) ≥ 15 Letters at 3 Months Compared to Baseline. | This is the regulatory filing primary outcome measure. Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. | Month 3 | 
| Proportion of Participants With a Reduction in Subretinal Fluid Volume ≥ 50% at 3 Months Compared to Baseline | This is the primary outcome measure for publication of study results. Subretinal fluid volume will be determined by manually moving the segmentation lines of the optical coherence tomography (OCT) image using the Edit Segmentation function of the Cirrus™ HD-OCT software. The segmentation lines will be edited to outline the inner and outer borders of the subretinal fluid pocket. This will be done manually for all the individual B-scans of each OCT image, after which the software algorithm automatically calculates the subretinal fluid volume. | Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Reactions Related to the Investigational Product | The outcome measure refers only to events that were classified as related to the investigational product. | Duration of the study, up to 1.5 years | 
| Number of Participants Who Withdrew From the Study |  | Duration of the study, up to 1.5 years | 
| Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at Month 3 Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome. | Month 3 | 
| Changes in Best-corrected Visual Acuity (BCVA) in the Study Eye at the Safety Visit Compared to Baseline | Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20. A positive change value indicates improvement of the outcome. A negative change value indicates worsening of the outcome. | Final Study Visit | 
| Percent Change in Subretinal Fluid Volume in the Study Eye at Month 3 Compared to Baseline | Subretinal fluid volume will be determined by manually moving the segmentation lines of the optical coherence tomography (OCT) image using the Edit Segmentation function of the Cirrus™ HD-OCT software. The segmentation lines will be edited to outline the inner and outer borders of the subretinal fluid pocket. This will be done manually for all the individual B-scans of each OCT image, after which the software algorithm automatically calculates the subretinal fluid volume. | Month 3 | 
| Changes in Mean Macular Sensitivity in the Study Eye at Month 3 Compared to Baseline | Microperimetry was used to assess macular sensitivity. | Month 3 | 
| Changes in Mean Macular Sensitivity in the Study Eye at the Safety Visit Compared to Baseline | Microperimetry was used to assess macular sensitivity. | Final Study Visit | 
| Change in Central Retinal Thickness in the Study Eye at Month 3 Compared to Baseline | Central retinal thickness was assessed by spectral-domain optical coherence tomography (SD-OCT). | Month 3 | 
| Change in Central Retinal Thickness in the Study Eye at the Safety Visit Compared to Baseline | Central retinal thickness was assessed by spectral-domain optical coherence tomography (SD-OCT). | Final Study Visit | 
| Change in Serum Dihydrotestosterone (DHT) Concentration at Month 3 Compared to Baseline | The mean change is reported in picograms of DHT per milliliter of serum. | Month 3 | 
| Change in Serum Dihydrotestosterone (DHT) Concentration at the Safety Visit Compared to Baseline | The mean change is reported in picograms of DHT per milliliter of serum. | Final Study Visit | 
| Change in Serum Testosterone Concentration at Month 3 Compared to Baseline | The mean change is reported in nanograms of testosterone per decaliter of serum. | Month 3 | 
| Change in Serum Testosterone Concentration at the Safety Visit Compared to Baseline | The mean change is reported in nanograms of testosterone per decaliter of serum. | Final Study Visit | 
| Change in Urinary Levels of Cortisol at Month 3 Compared to Baseline | The mean change is reported in micrograms (μg). | Month 3 | 
| Change in Urinary Levels of Cortisol at the Safety Visit Compared to Baseline | The mean change is reported in micrograms (μg). | Final Study Visit | 
| Number of Participants Presenting No Change in Autofluorescence Patterns at Month 3 Compared to Baseline | Autofluorescence patterns as observed on Fundus Autofluorescence (FAF) imaging | Month 3 | 
| Number of Participants Presenting No Change in Autofluorescence Patterns at the Safety Visit Compared to Baseline | Autofluorescence patterns as observed on Fundus Autofluorescence (FAF) imaging | Final Study Visit | 
| Number of Participants Presenting No Change in Size of Existing Plaque(s) on Indocyanine Green (ICG) Angiography at Month 3 Compared to Baseline |  | Month 3 | 
| Number of Participants Presenting No Change in Size of Existing Plaque(s) on Indocyanine Green (ICG) Angiography at the Safety Visit Compared to Baseline |  | Final Study Visit | 
| Number of Participants Presenting No Change in Fluid Leakage at Month 3 Compared to Baseline | Changes in leakage as observed on fluorescein angiography (FA) | Month 3 | 
| Number of Participants Presenting No Change in Fluid Leakage at the Safety Visit Compared to Baseline | Changes in leakage as observed on fluorescein angiography (FA) | Final Study Visit | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Finasteride, Central Serous Chorioretinopathy