First-in-Human Regulatory T Cell-Derived Exosomes Plus Ranibizumab for Refractory nAMD.

In 30 seconds

This single-centre, prospective, open-label phase 1a dose-escalation trial evaluated the safety and maximum tolerated dose of intravitreal autologous regulatory T cell-derived exosomes (TregExo) coformulated with ranibizumab in four people with refractory neovascular age-related macular degeneration and persistent fluid despite anti-VEGF treatment. Three participants received 0.05 mg and one received 0.5 mg. No dose-limiting toxicity occurred at 0.05 mg, while the 0.5-mg participant developed sterile intraocular inflammation with vision loss and a large intraretinal cyst. The protocol-defined maximum tolerated dose was 0.05 mg; dose escalation was stopped.

Key findings

• No dose-limiting toxicity or intraocular inflammation occurred among the three participants treated with 0.05 mg TregExo.
• The participant receiving 0.5 mg developed sterile intraocular inflammation, vision loss, and a large intraretinal cyst; these resolved after local corticosteroid therapy.
• Two low-dose participants’ ETDRS scores rose from baseline values of 3 and 9 to 35 at day 90.
• One low-dose participant’s macular thickness decreased from 318.2 to 253.9 µm.

Why it matters

The trial provides early human safety information for an investigational adjunct in nAMD with persistent fluid despite anti-VEGF treatment. The contrast between tolerability at 0.05 mg and dose-limiting toxicity at 0.5 mg highlights the importance of dose selection. Visual and anatomical changes are exploratory in this very small study and do not establish efficacy.

What to keep in mind

Only four participants were treated in a single-centre, open-label phase 1a trial. Visual and anatomical outcomes were exploratory, and follow-up was through day 90.