A Phase I Trial of TOR-582, a Topical Sirolimus-based Treatment for Epistaxis in Adults With Hereditary Hemorrhagic Telangiectasia
Columbia University
Summary
People with hereditary hemorrhagic telangiectasia (HHT) often experience frequent and severe nosebleeds that can disrupt daily life and lead to anemia, medical procedures, and reduced quality of life. This study is testing a new nasal ointment called TOR-582, which contains sirolimus, to determine whether it can be used safely when applied inside the nose. Adults with HHT and frequent nosebleeds will be invited to participate. Participants will first complete one week of observation without treatment, followed by up to 12 weeks of applying the study ointment inside each nostril twice daily. Different participants will receive different strengths of the ointment so researchers can identify the safest dose. During the study, participants will attend study visits, complete questionnaires about their nosebleeds and quality of life, keep a daily nosebleed diary, undergo nasal examinations, and have blood tests to monitor safety and medication levels. The information gained from this study will help determine whether this topical treatment can be safely studied further and will support the development of a new, less invasive option for managing nosebleeds in people with HHT.
Description
This is a Phase I single-center trial evaluating the safety, tolerability, and clinical activity of TOR-582 in adults with HHT-associated epistaxis. The study will include a Phase 1a Dose-Finding study and a preliminary Proof-of-Concept protocol. The study will employ a Bayesian Optimal Interval (BOIN) dose-finding design with accelerated titration. Phase 1a will commence with topical administration of the TOR-582 compound in the nasal cavity, starting with a 1% dose (.2mL, dose level 2) delivered twice daily for a 12-week dosing period. Participants will complete a 1-week observational basel…