Faricimab for Chronic Central Serous Chorioretinopathy: A Randomized Sham-Controlled Trial

Official title

A Randomized, Double-Masked, Sham-Controlled Clinical Trial of Intravitreal Faricimab for Chronic Central Serous Chorioretinopathy With or Without Secondary Macular Neovascularization: Study Protocol for a Randomised, Double-Masked Trial

Overview

Dysregulation of the Angiopoietin-2 (Ang-2)/Tyrosine kinase with Immunoglobulin-like and EGF-like domains 2 (Tie-2) signaling pathway has been implicated in choroidal vascular instability and RPE dysfunction in Central serous chorioretinopathy (CSCR) and pachychoroid-associated neovascularization. This study prospectively evaluates the efficacy and safety of faricimab compared to sham in CSCR with and without secondary neovascularization, using standardized anatomical and functional endpoints. The results of this trial may help define the role of dual pathway inhibition in CSCR and inform future treatment strategies for this challenging and vision threatening condition.

Detailed description

Current understanding of central serous chorioretinopathy (CSCR) pathophysiology has evolved from a localized retinal disorder to a disease driven primarily by choroidal venous congestion, vascular hyperpermeability, and hemodynamic dysfunction. The current treatment of choice is photodynamic therapy (PDT). However, there is a global shortage of the photosensitive dye (Verteporfin) which is required for PDT. In addition, special laser and angiography equipment are required to deliver PDT, further limiting the access to this treatment.

Persistent subretinal fluid and neovascular complications represent unmet clinical challenges in the management of CSCR and pachychoroid-associated disease. Emerging evidence from genetic studies suggests that the Angiopoietin-2 (Ang-2) pathway plays a direct role in retinal pigment epithelium (RPE) dysfunction and choroidal vascular instability, along with Tie2 receptor. These mechanisms are also believed to contribute to the choroidal congestion and subretinal fluid accumulation seen in CSCR.

The dual inhibition of Vascular Endothelial Growth Factor (VEGF)-A and Ang-2 offered by faricimab provides a mechanistic rationale for evaluating its efficacy in eyes with CSCR. To-date, only small observational studies and case series have reported macular fluid reduction following intravitreal faricimab. However, these studies are limited by small sample sizes and the absence of comparator groups, hence the need for more robust clinical evidence.

Specific aim: To evaluate the efficacy and safety of intravitreal faricimab in achieving anatomical improvements compared with sham treatment in patients with retinal fluid secondary to CSCR with/ without neovascularization.

Hypothesis: Intravitreal faricimab, through its dual inhibition of VEGF-A and Ang -2, will result in superior drying effect compared with sham treatment.

Interventions

• Drug Faricimab
  Intravitreal faricimab 6 mg at baseline, month 1, and month 2, followed by protocol-defined Pro Re Nata (PRN) dosing at monthly visits through Month 6.
• Drug Sham
  Sham injections at baseline, month 1, and month 2. After assessment of the primary endpoint at Month 3, participants randomized to the sham arm who demonstrate persistent intraretinal and/or subretinal fluid will switch to intravitreal faricimab treatment by protocol-defined PRN dosing at monthly visits through Month 6.

Primary outcome measures

• The efficacy of 3 loading doses of IVT faricimab compared with sham treatment in achieving anatomical improvement in eyes with chronic CSCR with presence of foveal sub-retinal fluid (SRF), with or without secondary macular neoascularization (MNV). [Time frame: 3 months.]

Secondary outcome measures (12)

• The proportion of eyes achieving a ≥20% reduction in central retinal thickness (CRT) from baseline at month 3 and month 6. [Time frame: 6 months.]
• The proportion of eyes achieving complete resolution of intraretinal and/or SRF from month 1 through month 6. [Time frame: 6 months.]
• The time to first resolution of intraretinal and/or SRF. [Time frame: 6 months.]
• The mean change in best corrected visual acuity (BCVA) from baseline to months 3 and 6. [Time frame: 6 months.]
• The mean change in CRT from baseline to months 3 and 6. [Time frame: 6 months.]
• The number of intravitreal faricimab injections administered from baseline through month 6. [Time frame: 6 months.]
• Changes in subfoveal choroidal thickness (SFCT) measured by Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) from baseline to months 3 and 6. [Time frame: Measurements will be obtained at baseline, Month 3, and Month 6, from the central foveal B-scan.]
• The proportion of eyes demonstrating reduction in height or resolution of pigment epithelial detachment (PED). [Time frame: 6 months.]
• Exploratory Analysis of Baseline Qualitative OCT Structural Features as Predictors of Treatment Response. [Time frame: Baseline imaging with outcome assessed at Month 3 and at Month 6.]
• Exploratory Analysis of Baseline Choroidal Vascularity Index (CVI) as a Predictor of Treatment Response. [Time frame: Baseline imaging with outcome assessed at Month 3 and at Month 6.]
• Exploratory Analysis of Baseline Presence of Macular Neovascularization (MNV) on OCT Angiography as a Predictor of Treatment Response. [Time frame: Baseline imaging with outcome assessed at Month 3 and at Month 6.]
• The correlation between baseline MNV lesion area measured on OCT angiography and treatment response will be evaluated. [Time frame: Baseline imaging with outcome assessed at Month 3 and at Month 6.]

Eligibility criteria

Inclusion criteria

• Age ≥21 years at the time of consent.
• Best corrected visual acuity between 24 and 73 ETDRS letters (approximately Snellen equivalent 20/32 to 20/300) in the study eye.
• Diagnosis of chronic CSCR, defined as the presence of persistent SRF for ≥3 months, with or without secondary MNV.
• Presence of pachychoroid features, including pachyvessels on ultra-widefield imaging in at least one quadrant and SFCT ≥300 µm.
• Presence of intraretinal fluid and/or subretinal fluid involving the fovea, as confirmed by OCT.
• Disease duration criteria:

• CSCR without secondary MNV: persistent subretinal fluid for ≥3 months despite observation, or
• CSCR with secondary MNV: presence of exudative fluid of any duration, with neovascularization confirmed on OCTA.
• Ability and willingness to provide written informed consent.
• Women of childbearing potential must have a negative pregnancy test prior to enrollment and agree to use a reliable form of contraception for the duration of the study.

Exclusion criteria

• Presence of ocular inflammation or primary choroidal disorders.
• Presence of polypoidal choroidal vasculopathy (PCV).
• Any ocular condition that, in the opinion of the investigator, could affect intra- or subretinal fluid or significantly alter visual acuity during the study (e.g., diabetic macular edema, retinal vein occlusion, uveitis, neovascular glaucoma).
• Clinically significant cataract likely to reduce visual acuity by more than three ETDRS lines (i.e., worse than approximately 20/40 if the eye were otherwise normal).
• Any intraocular surgery within 3 months prior to enrollment.
• Prior treatment in the study eye with:

• Intravitreal corticosteroids (any time),
• Anti-VEGF therapy within 6 months, or
• Photodynamic therapy (any time).
• History of retinal detachment or surgery for retinal detachment, prior vitrectomy, or presence of a full-thickness macular hole.
• Evidence of vitreomacular traction that may preclude resolution of macular edema.
• Extensive intra- or subretinal hemorrhage exceeding 4 disc areas.
• Aphakia in the study eye.
• Pregnancy or breastfeeding.
• Any medical, psychiatric, or systemic condition that, in the opinion of the investigator, would make study participation unsafe or interfere with study assessments.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07681167 · TBC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗