BACKGROUND

JNJ-81201887, an investigational, recombinant adeno-associated viral vector (AAVCAGsCD59) serotype 2 that expresses soluble CD59, is being studied for the treatment of geographic atrophy (GA) and wet age-related macular degeneration (AMD). Soluble CD59 (sCD59), an endogenous protein that inhibits the formation of membrane attack complex (MAC), is intended to protect retinal cells to slow and prevent disease progression via a single, in-office intravitreal injection. Accumulation of MAC on cell surfaces, including drusen, leads to cell damage and cell death. Inhibition of MAC formation is hypothesized to protect retinal cells that are responsible for central vision and preserve functional vision.^1-4

CLINICAL DATA

PARASOL Study

Study Design⁵

The PARASOL⁶ study is a phase 2b, randomized, double-masked, multicenter, dose-ranging, sham-controlled clinical trial currently ongoing to evaluate intravitreal JNJ-81201887 (AAVCAGsCD59) compared to sham procedure for the treatment of GA secondary to AMD. Please visit https://clinicaltrials.gov/study/NCT05811351">https://clinicaltrials.gov

The PARASOL study has 2 experimental treatment arms and 1 sham comparator arm with an estimated enrollment of 300 participants total. In the experimental arms, participants will receive either a single low or high dose intravitreal injection of JNJ-81201887 in the study eye on day 4. In addition, participants in both experimental arms will receive a 20-day oral prednisone course starting on day 1 and a single, long acting periocular triamcinolone injection on day 4 for prophylaxis of intraocular inflammation. In the sham comparator arm, participants will receive sham procedures that match the single JNJ-81201887 injection and long acting corticosteroid injection (triamcinolone) on day 4, and a 20-day placebo matching oral prednisone course starting on day 1.

Inclusion Criteria⁵

Inclusion criteria include male or female sex, 60 years of age or older, and:

• Have non-subfoveal (defined as not having the center point of the fovea) GA secondary to AMD with an area that can be measured and measures 2.5 mm² to 17.5 mm² (1- and 7- disc areas, respectively), determined by the central reading center (CRC) from screening images of fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT)
• If GA is multifocal, at least 1 focal lesion must be ≥1.25 mm² (0.5- disc area), as assessed by the CRC
• GA can be photographed in its entirety by FAF, using a 30-degree image centered on the fovea, as assessed by the CRC
• Fellow eye must be present with a best corrected distance visual acuity (BCVA) of counting fingers or better

Exclusion Criteria⁵

• History of transpupillary thermotherapy, photodynamic therapy or external-beam radiation therapy in the region of study eye
• Any prior thermal laser in the macular region, regardless of indication
• History of retinal detachment (with or without repair)
• Active, infectious conjunctivitis, keratitis, scleritis, or endophthalmitis
• Any sign of diabetic retinopathy or central serous chorioretinopathy

Primary and Secondary Outcomes⁵

The primary outcome is change from baseline in square root of GA lesion area in the study eye at month 18 measured by retinal imaging using FAF.

The secondary outcomes, measured as change from baseline at month 18, are as follows:

• Best corrected low luminance visual acuity using the early treatment diabetic retinopathy study (ETDRS) chart at a starting distance of 4 meters
• Reading speed (normal luminance) as assessed by Radner reading charts will be performed in the study eye and binocularly for participants who are fluent in the languages available for the Radner Chart
• Retinal sensitivity by mesopic microperimetry
• BCVA measured using the ETDRS chart at a starting distance of 4 meters
• Functional Reading Independence Index
• National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25) Composite score

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, and DERWENT^® (and/or other resources, including internal/external databases) was conducted on 24 April 2024.