Assess Safety and Efficacy of VAD044 in HHT Patients

Part I: After being informed about the study and the potential risks, all patients giving written informed consent will undergo a two months screening and observation period to determine eligibility for study entry. At Day 0, patients who meet the eligibility requirements will be randomized in a double-blind manner (participant and investigator) in a 1:1:1 ratio to 30mg VAD044 (once daily), 40 mg (once daily) or placebo (once daily).

Part II: Patients who have completed the study Part I can participate in the open-label extension study (Part II).The patients can roll over immediately after last visit of the Part I or at any time at their convenience and according to their availability, but within a timeframe no longer than 8 months after the last visit (visit 12) of the part I. All patients in Part II will receive 30 mg of VAD044 once daily for the first 4 weeks afterwards the daily dose can be increased to 40 mg daily for up to 36 months.

For Part I of the study:

Inclusion criteria

• Diagnosis of HHT by the Curaçao criteria
• Several epistaxis/week
• Anaemia
• COVID-19 vaccination or positive COVID-19 antibody test
• Patient has given written informed consent to participate in Part I

Exclusion criteria

• Type 1 diabetes or uncontrolled type II diabetes (insulin or non-insulin dependent)
• Active COVID-19 infection
• active uncontrolled infection or known to be serologically positive for HIV, Hep B, Hep C infection
• Recent procedures on nasal telangiectases (<6 weeks)
• Requiring therapeutic anticoagulation
• Use of drugs with anti-angiogenic properties in the past 8 weeks
• laboratory abnormalities

Fort Part II of the study:

Inclusion criteria

• Completion of Part I of the study
• All adverse events or serious adverse events occuring during Part I of the study have resolved
• Patient has given written informed consent to participate in Part II

Exclusion criteria

• Same as in Part I.