Assess Safety and Efficacy of VAD044 in HHT Patients

Study Overview
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Brief Summary
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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

Detailed Description
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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)

Official Title
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A Randomised, Placebo Controlled, Double Blind, Multicentre Proof of Concept Study to Assess the Safety and Efficacy of Two Doses of VAD044 in Patients With Hereditary Hemorrhagic Telangiectasia (HHT)

Conditions
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Hereditary Hemorrhagic Telangiectasia (HHT)

Intervention / Treatment
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* Drug: VAD044


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of HHT by the Curaçao criteria several epistaxis/week anaemia COVID-19 vaccination or positive COVID-19 antibody test 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The patients will be randomised into VAD044 30 mg or 40 mg or placebo group in the ratio 1:1:1, according to a centralised randomisation process
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 30 mg<br>30 mg VAD044 | Drug: VAD044<br>* capsules to be taken once daily for 12 weeks<br>* Other names: VAD044 L-Tartrate gelatin capsules;|
| Experimental: 40 mg<br>40 mg VAD044 | Drug: VAD044<br>* capsules to be taken once daily for 12 weeks<br>* Other names: VAD044 L-Tartrate gelatin capsules;|
| Placebo Comparator: Placebo<br>Placebo | Drug: VAD044<br>* capsules to be taken once daily for 12 weeks<br>* Other names: VAD044 L-Tartrate gelatin capsules;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Type and severity of Adverse Events (AEs) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Epistaxis Frequency | The number of Epistaxis episodes over four weeks | 12 weeks | 
| Pharmacokinetics (PK) of VAD044 | Plasma concentration of VAD044 | 12 weeks | 
| Change in the Nasal Outcome for Epistaxis in Hereditary Hemorrhagic Telangiectasia score | The Nasal Outcome for Epistaxis in Hereditary Hemorrhagic Telangiectasia (NOSE HHT questionnaire) wil be used to measure physical, social and emotional impacts of epistaxis. It is a 29-items questionnaire using a Likert scale. A higher score indicates a worse outcome | 12 weeks | 
| Quality of Life Scale SF-12 | The SF-12 Quality of Life Scale is a scale to evaluate quality of life using 12 questions. In the SF-12, physical (SF12-PCS) and mental (SF12-MCS) component summary scores are calculated as sub-dimensions. The total score of the physical and mental component summary of the scale varies between 0-100. An increase in the score indicates well-being, and a decrease indicates a state of disability. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osler-Weber-Rendu disease, Arteriovenous Malformations