Short-Term Oral Mifepristone for Central Serous Chorioretinopathy

Overview

The goal of the study is to assess the efficacy and safety of mifepristone 300 or 900-mg once-daily dosing by mouth for 4 weeks in patients with central serous chorioretinopathy.

Full Title of Study: “Short-Term Oral Mifepristone for Central Serous Chorioretinopathy. A Placebo-controlled Dose Ranging Study of Mifepristone in the Treatment of CSC (STOMP-CSC)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: April 27, 2017

Detailed Description

– Prospective, randomized, double-masked, placebo-controlled dose-ranging study – Eligible patients will be those with CSC, with symptoms of blurred or distorted vision, with the presence of sub-retinal fluid as documented on optical coherence tomography (OCT) in the central foveal sub-field – Only one eye of a participant will be included in the study, although both eyes will be evaluated. In patients with bilateral CSC, the eye with more sub-foveal fluid on OCT will be the study eye. – Patients will be evaluated and treated at one of two study centers: Ophthalmic Consultants of Boston (OCB), 50 Staniford St., Suite 600, Boston, MA Bay Area Retina Associates (BARA), 122 La Casa Via, Suite 223, Walnut Creek, CA – All participants will receive a standard ophthalmic examination as well as fluorescein and indocyanine green angiography and macular OCT per protocol. – 30 patients will be enrolled, as follows: 10 patients will be randomly assigned to Cohort 1, and will take one (1) mifepristone 300-mg tablet (300 mg total dose) once daily by mouth for 4 weeks. 10 patients will be randomly assigned to Cohort 2, and will take three (3) mifepristone 300-mg tablet (900 mg total dose) once daily by mouth for 4 weeks. 10 patients will be randomly assigned to Cohort 3, and will take placebo tablet(s) once daily by mouth for 4 weeks. – After completing the enrollment criteria, a subject will be randomized 1:1:1 to Cohort 1, 2, or 3. – During the Baseline visit and at the Week 2, 4, and 8 visits, all subjects will have laboratory testing of the following lab tests: serum electrolytes, BUN and creatinine, liver function tests – Prior to initiating dosing of the study drug, all women of child-bearing potential (WOCBP) will have a serum beta-HCG assessed to rule out pregnancy; all WOCBP who are enrolled in the study will be required to use barrier contraception throughout the study. – Adverse events will be tracked at each visit (see "Data Safety and Monitoring Plan" below)

Interventions

  • Drug: Mifepristone
  • Drug: Placebo

Arms, Groups and Cohorts

  • Experimental: Cohort 1 (m300)
    • One (1) 300-mg mifepristone tablet, taken once daily for 4 weeks
  • Experimental: Cohort 2 (m900)
    • Three (3) 300-mg mifepristone tablets (900-mg dose), taken once daily for 4 weeks
  • Placebo Comparator: Cohort 3 (Placebo)
    • Placebo taken once daily for 4 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Resolution of Sub-retinal Fluid
    • Time Frame: 4 weeks after treatment
    • Presence or absence of subretinal fluid on spectral-domain OCT after 4 weeks of treatment with mifepristone 300 or 900 mg daily, compared with placebo.

Secondary Measures

  • Change in sub-retinal fluid and/or intraretinal fluid
    • Time Frame: Week 1, 2, 4, and 8
    • Change compared to Baseline in subretinal fluid and/or intraretinal fluid on OCT at Week 1, 2, 4, and 8,
  • Best Corrected Visual Acuity
    • Time Frame: Week 1, 2, 4, and 8
    • Change compared to Baseline in ETDRS BCVA at Week 1, 2, 4, and 8.
  • Change in macular thickness
    • Time Frame: Week 1, 2, 4, and 8
    • Change compared to Baseline in central macular circle thickness on OCT, automatically calculated with OCT software at Week 1, 2, 4, and 8.
  • Change in foveal thickness
    • Time Frame: Week 1, 2, 4, and 8
    • Change compared to Baseline in thickness of subretinal fluid under the fovea on OCT, manually calculated at Week 1, 2, 4, and 8
  • Change in choroidal thickness
    • Time Frame: Week 1, 2, 4, and 8
    • Change compared to Baseline in thickness of choroid under the fovea on enhanced-depth imaging OCT, manually calculated, at Week 1, 2, 4, and 8.
  • Dye leakage in vasculature
    • Time Frame: Week 4 and 8
    • Change compared to Baseline in dye leakage characteristics on fluorescein and indocyanine green angiography at Week 4 and Week 8.
  • Change in OCT characteristics in the fellow eye
    • Time Frame: Week 8
    • Change compared to Baseline in the same OCT characteristics listed above, in the fellow eye.
  • Proportion of acute vs. chronic CSC patients
    • Time Frame: Week 8
    • Proportion of acute versus chronic CSC patients as determined at Baseline, with the above outcomes analyzed for each sub-group.
  • Safety and Tolerability Characteristics
    • Time Frame: Week 8
    • Safety and tolerability characteristics in this patient population via clinical laboratory data and adverse events

Participating in This Clinical Trial

Inclusion Criteria

1. Diagnosis of central serous chorioretinopathy (CSC) with symptoms 6 weeks or prior documented episodes of sub-retinal fluid; patients who have had previous treatment for CSC may be included 2. Presence of sub-retinal fluid as documented on optical coherence tomography (OCT) in the central foveal sub-field 3. Age 18 or over 4. Willing and able to comply with clinic visits and study-related procedures 5. Ability to give written informed consent Exclusion Criteria:

1. Age less than 18 2. Persons with impaired decision-making ability. 3. Women who are known to be breast-feeding, pregnant or are actively trying to conceive. 4. Additional eye disease affecting the macula, posterior retina, or ocular media that would limit or prevent the acquisition of OCT and angiographic images. 5. At screening, serum potassium < LLN, BUN > 1.5 ULN, serum creatinine >1.5 ULN, AST > 1.5 ULN, ALT >1.5 ULN, bilirubin > 1.5 ULN, alkaline phosphatase > 1.5 ULN, serum albumin >1.5 ULN or <LLN. 6. Intraocular surgery (including cataract surgery) in the study eye within 60 days preceding baseline. 7. Active intraocular inflammation (grade trace or above) in the study eye. 8. Patients taking simvastatin, lovastatin, and CYP3A substrates with narrow therapeutic ranges, such as cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. 9. Patients who require concomitant treatment with systemic corticosteroids for serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation). 10. Women with a history of unexplained vaginal bleeding and women with endometrial hyperplasia with atypia or endometrial carcinoma. 11. Patients with prior hypersensitivity reactions to mifepristone or to any of the product components. 12. Patients with known hypersensitivity to fluorescein or indocyanine green dyes.

  • WOCBP must be willing to practice adequate contraception during the study (adequate contraceptive measures include intrauterine device [IUD]; bilateral tubal ligation; condom plus contraceptive sponge, foam, or jelly, or diaphragm plus contraceptive sponge, foam, or jelly). Postmenopausal women must be amenorrheic for at least 12 months in order not to be considered of child bearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Roger Goldberg, M.D., MBA
  • Collaborator
    • Ophthalmic Consultants of Boston
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Roger Goldberg, M.D., MBA, Ophthalmologist, Retina and Vitreous – Bay Area Retina Associates
  • Overall Official(s)
    • Roger A Goldberg, M.D., MBA, Principal Investigator, Bay Area Retina Associates
    • Jeffrey S Heier, M.D., Principal Investigator, Ophthalmic Consultants of Boston

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