Abstract ID: 26-293
Design of the RECLAIM Study: A Phase 1/2 Trial of an AAV Gene Therapy Expressing an Anti-IGF1R Antibody, for Thyroid Eye Disease
Author: Steven Leibowitz Base Hospital / Institution: Stein Eye Institute, UCLA
Presentation Type: Oral Presentation Session: OrbitDate: 11th SeptemberTime: 15.05
Purpose
Current thyroid eye disease (TED) treatments require repeated systemic administration, have adverse effects, and do not prevent recurrence, representing an unmet need. VV-14305 is an investigational AAV9 gene therapy expressing an anti-IGF1R antibody via one-time peribulbar injection for TED. The encoded antibody has shown biological activity comparable to teprotumumab in vitro and in vivo. Here we describe the design of the RECLAIM study evaluating VV-14305 in patients with TED.
Methods
Previous studies in nonhuman primates (NHPs) compared orbital anti-IGF1R antibody concentrations following IV teprotumumab versus peribulbar VV-14305. RECLAIM is a global Phase 1/2 adaptive dose-escalation multicenter study enrolling adults aged 18-80 with chronic moderate-to-severe TED per 2021 EUGOGO guidelines, proptosis ≥3 mm above normal, clinical activity score 0-4, BMI 19-34 kg/m², and excluding women of childbearing potential. Eligible patients receive a peribulbar injection of VV-14305 in a one-time outpatient procedure and are followed for 52 weeks.
Results
In NHP studies, peribulbar VV-14305 achieved orbital anti-IGF1R antibody concentrations comparable to IV teprotumumab, with minimal systemic exposure. Clinical trial primary endpoints include incidence and severity of adverse events, tolerability, and proptosis responder rate. Key secondary endpoints include changes in proptosis, diplopia, clinical activity score, extraocular muscle volume, and quality of life.
Conclusion
VV-14305 may offer a durable, local treatment for TED, potentially addressing limitations of systemically administered anti-IGF1R therapies. Moreover, new manufacturing technologies have made gene therapy for TED economically viable. The RECLAIM study is currently enrolling globally.