March 25, 2026 —
Complement Therapeutics has announced that the first patient has been dosed in the Opti-GAIN Phase 1/2 clinical trial, evaluating CTx001, an investigational AAV2-based gene therapy for geographic atrophy (GA) secondary to age-related macular degeneration (AMD). The milestone marks the initiation of first-in-human clinical testing of the therapy.
The Opti-GAIN study is a multi-center Phase 1/2 trial designed to evaluate the safety, tolerability, and preliminary efficacy of CTx001 following a single subretinal injection. The trial begins with an open-label dose-escalation phase across three dose cohorts, followed by a dose-expansion stage to further assess clinical activity.
CTx001 is designed as a one-time AAV gene therapy that delivers mini-CR1, a truncated and secreted form of Complement Receptor 1 (CR1). The therapy aims to modulate multiple components of the complement system, including both the classical and alternative pathways, which are known to play a key role in the pathogenesis of geographic atrophy.
Using an AAV2 vector, CTx001 enables retinal cells to produce mini-CR1 locally following subretinal delivery. The compact size of mini-CR1 may also allow diffusion across Bruch’s membrane, potentially enabling broad ocular distribution, including the choriocapillaris, which could enhance therapeutic coverage within the eye.
The development strategy for CTx001 is supported by Pre-GAIN, an ongoing natural history study designed to better understand short-term progression of GA and support the development of new clinical endpoints. Conducted across the United States and the United Kingdom, the study is helping characterize structural and functional disease markers while informing patient selection for the Opti-GAIN interventional trial.
Together, the Opti-GAIN and Pre-GAIN programs aim to advance clinical development by integrating natural history insights with therapeutic intervention data. The studies are also evaluating emerging functional and structural endpoints, including ellipsoid zone (EZ) integrity and focal optical coherence tomography (OCT)-based microperimetry, which may improve the assessment of treatment response in GA.
Geographic atrophy represents an advanced form of AMD characterized by progressive degeneration of retinal cells and irreversible central vision loss. Although recent therapies targeting the complement pathway have been approved, treatment options remain limited and require frequent injections, highlighting the potential value of durable gene therapy approaches.
By enabling long-term modulation of complement biology through a single AAV-mediated treatment, CTx001 could offer a new therapeutic strategy for patients with GA. The Opti-GAIN study will enroll approximately 75 participants, with safety and efficacy monitored over two years, followed by extended long-term follow-up for up to five years.
If successful, the program may further demonstrate the potential of AAV gene therapy in ophthalmology, particularly for chronic retinal diseases where sustained biological modulation may provide long-lasting clinical benefit.
