Clinical Research Directory

Harmony-HHT: ATV-1601 in Participants With Hereditary Hemorrhagic Telangiectasia (HHT)

This is a 2-part study evaluating ATV-1601 in participants with moderate to severe HHT. Part 1 is a randomized, double-blind, placebo-controlled study evaluating 3 dosing regimens of ATV-1601. Patients completing Part 1 may participate in the Part 2 open-label extension to receive ATV-1601.

Topical TOR-582 Treatment of Epistaxis in HHT

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.

IV Bevacizumab Treatment of Patients With Hereditary Hemorrhagic Telangiectasia (HHT) or Rendu-Osler (RO) Disease: A Retrospective Analysis of French Cohort Data From 2009 to 2024

Rendu-Osler disease (RO), also known as Hereditary Haemorrhagic Telangiectasia (HHT), is an autosomal dominant genetic disorder. Its pathophysiology is associated with an imbalance in angiogenic balance. The resulting epistaxis and digestive bleeding can be severe, requiring repeated transfusions in 5% of patients. In addition, some patients with HHT may present with liver damage, leading to high-flow heart failure. Vascular Endothelial Growth Factor (VEGF) plays a role in the pathophysiology of Rendu-Osler disease, leading to the use of a recombinant anti-VEGF monoclonal antibody, bevacizumab. Studies conducted and promoted by HCL have demonstrated the efficacy and safety of bevacizumab in patients with HHT. In 2014, bevacizumab was granted orphan drug designation for this disease. The 2020 international guidelines for the diagnosis and management of HHT suggest the use of systemic antiangiogenic agents in cases of epistaxis resistant to other treatments. The use of bevacizumab has been widely published in uncontrolled studies, demonstrating its efficacy in reducing epistaxis, improving anaemia, reducing transfusion dependence and improving quality of life. In France, bevacizumab is currently prescribed outside the scope of its marketing authorization. Treatment indications are validated within the French network of expert centres and the FAVAmulti rare disease network. In other countries, access to this treatment varies widely according to local regulations, and is currently being evaluated in the European VASCERN network. The aim of this study is to describe the use of bevacizumab in patients treated for HHT in France.

Pomalidomide for the Treatment of Bleeding in Hereditary Hemorrhagic Telangiectasia Longitudinal Assessment Study

This is a multicenter U.S. longitudinal study evaluating patients with hereditary hemorrhagic telangiectasia who participated in the PATH-HHT clinical trial of pomalidomide for the treatment of HHT. This study is a longitudinal assessment of safety and effectiveness of pomalidomide in HHT in clinical trial participants following completion of the double-blind, placebo-controlled study.

A Trial of TER-1754 in Patients With Hereditary Hemorrhagic Telangiectasia

This is a Phase 1a/1b, multicenter study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of TER-1754 (a novel AKT1 inhibitor) in patients with HHT.

Assess Safety and Efficacy of VAD044 in HHT Patients

Part I: The purpose of this Phase 1b proof of concept study, randomised, placebo controlled, double blind, multicentre study is to asssess safety and efficacy of 2 doses of VAD044 in adult HHT patients. Part II: The purpose of this open-label extension following the completion of the randomised double blind treatment and follow-up period (Part I of the study) is to assess the long-term safetty, tolerability and efficacy of VAD044 in adult HHT patients.

Efficacy and Tolerance of Treatment With Bevacizumab for Severe Liver Involvement With High Cardiac Output in Hereditary Hemorrhagic Telangiectasia Within the French Hereditary Hemorrhagic Telangiectasia Network

High cardiac output secondary to hepatic arteriovenous malformations may be isolated or associated with left heart failure with post-capillary pulmonary hypertension. More rarely, precapillary pulmonary hypertension develops, linked to obstructive pulmonary arterial remodeling, referred to as pulmonary arterial hypertension (PAH), which affects younger patients and is not necessarily associated with hepatic arteriovenous malformation. BEVACIZUMAB is an anti-VEGF treatment indicated under compassionate use guidelines for hereditary hemorrhagic telangiectasia in cases of symptomatic hepatic arteriovenous malformations, when complicated by isolated high cardiac output or post-capillary pulmonary hypertension, and in cases of refractory chronic bleeding. However, the efficacy of this treatment on pulmonary hypertension related to high cardiac output, isolated or associated with left heart failure, is poorly understood. In addition, this treatment is classified as a "possible association" for the development of PAH, according to the 7th World Congress Symposium on Pulmonary Hypertension. Indeed, Hlavaty et al. found, based on pharmacovigilance data and by searching for disproportionate effects using the Bayesian network method, a possible link between the use of BEVACIZUMAB and the development of PAH. This treatment is therefore not recommended in cases of PAH associated with hereditary hemorrhagic telangiectasia. The objective of this study is to investigate the efficacy and tolerability of Bevacizumab treatment in hereditary hemorrhagic telangiectasia with cardiac involvement (isolated symptomatic high cardiac output or associated with post-capillary PAH) secondary to severe liver damage, based on the experience of the French hereditary hemorrhagic telangiectasia network since the CIROCO registry was opened in 2009.