Topical Sirolimus for Nosebleeds in HHT

This trial tests a nasal ointment called TOR-582, containing sirolimus, to determine its safety and effectiveness for people with hereditary hemorrhagic telangiectasia (HHT) who suffer from frequent and severe nosebleeds. The goal is to find a less invasive way to manage these nosebleeds and improve quality of life. Participants will apply the ointment inside their nostrils twice daily for up to 12 weeks, with different strengths tested to identify the safest dose. Adults with HHT who experience at least four spontaneous nosebleeds a week and have stable nosebleed patterns are suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Research has shown that sirolimus is safe and effective for treating certain conditions, such as blue rubber bleb nevus syndrome, a rare disorder. This finding provides reassurance about its safety. Sirolimus has been tested in various forms, including as a pill, and studies have demonstrated a good safety record. Although limited information exists on using sirolimus as a cream for nosebleeds in people with hereditary hemorrhagic telangiectasia (HHT), research on sirolimus for other uses suggests it is generally well-tolerated. Participants in previous studies did not report major side effects, which is encouraging for those considering joining a clinical trial.¹²³⁴⁵

Unlike the standard treatments for nosebleeds in HHT, which often include nasal cauterization or systemic medications, the topical sirolimus ointment offers a novel approach. It works by directly targeting the affected area in the nose with a localized application, potentially reducing systemic side effects. Sirolimus is known for its anti-inflammatory and anti-angiogenic properties, which may help reduce the frequency and severity of nosebleeds by stabilizing blood vessels. Researchers are excited because this approach could provide a safer, more effective treatment option with fewer side effects compared to existing therapies.

Studies have shown that sirolimus can help control unusual blood vessel growth, common in people with hereditary hemorrhagic telangiectasia (HHT). Research suggests it can reduce bleeding episodes, such as nosebleeds, by stabilizing these blood vessels. In other conditions with similar blood vessel issues, sirolimus has proven effective even at low doses, minimizing side effects. A small study found that sirolimus could treat moderate to severe nosebleeds in HHT patients. This trial will test different concentrations of topical sirolimus ointment to evaluate its effectiveness in reducing the frequency and severity of nosebleeds in HHT. Early research indicates that sirolimus ointment could be a promising option for this purpose.²⁴⁵⁶⁷