Assess Safety and Efficacy of VAD044 in HHT Patients

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hereditary Hemorrhagic Telangiectasia (HHT)
• Intervention / Treatment: Drug: VAD044 Part I; Drug: VAD044 Part II

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium
    • Universitair Ziekenhuis Gent
• France
  • Lyon, France
    • Hospices Civils de Lyon
• Italy
  • Crema, Italy
    • Ospedale Maggiore di Crema
• Netherlands
  • Nieuwegein, Netherlands
    • St. Antonius Hospital
• Spain
  • Barcelona, Spain
    • Hospital Universiati De Bellvitge
  • Madrid, Spain
    • Hospital Universitario Ramón y Cajal
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: VAD044 Part I; capsules to be taken once daily for 12 weeks; Other Names: VAD044 L-Tartrate gelatin capsules
Experimental: 30 mg; 30 mg VAD044	Drug: VAD044 Part I; capsules to be taken once daily for 12 weeks; Other Names: VAD044 L-Tartrate gelatin capsules; Drug: VAD044 Part II; capsules to be taken once daily for 36 months; Other Names: VAD044 L-Tartrate gelatin capsules
Experimental: 40 mg; 40 mg VAD044	Drug: VAD044 Part I; capsules to be taken once daily for 12 weeks; Other Names: VAD044 L-Tartrate gelatin capsules; Drug: VAD044 Part II; capsules to be taken once daily for 36 months; Other Names: VAD044 L-Tartrate gelatin capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part I: Safety and Tolerability	Type and severity of Adverse Events (AEs)	12 weeks
Part II: Safety and Tolerability	Type and severity of Adverse Events (AEs)	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part I: Change in Epistaxis episodes	The number of Epistaxis episodes	12 weeks
Part I: Change in Epistaxis duration	Epistaxis duration	12 weeks
Part I: Change in Epistaxis intensity	Epistaxis flow intensity	12 weeks
Part I: Change in Epistaxis Severity Score (ESS)	ESS used to evaluate the current severity of HHT patient nosebleeds (typically in the last three months) and can help health care providers to evaluate how a patient is responding to treatment. This score ranges from 0-10 and is automatically calculated after answering six simple questions. The higher the score the more severe.	12 weeks
Part I: Change in Haemoglobin	Haemoglobin	12 weeks
Part I: Change Ferritin	Ferritin	12 weeks
Part I: Change in blood Transferrin saturation level	Transferrin saturation level	12 weeks
Part I: Change in Iron supplementation needs	Iron supplementation needs	12 weeks
Part I: Change Blood tranfusions requirements	Blood tranfusions requirements	12 weeks
Part I: 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
Part I: 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
Part I: Plasma concentration of VAD044	Plasma concentration of VAD044	12 weeks
Part I: Maximum concentration (Cmax) of VAD04	Maximum concentration (Cmax) of VAD044	12 weeks
Part I: Time of maximum concentration (Tmax) of VAD044	Time of maximum concentration (Tmax) of VAD044	12 weeks
Part I: Area under the curve (exposure to drug) during 24 hours (AUC0-24h) of VAD044	Area under the curve (exposure to drug) during 24 hours (AUC0-24h) of VAD044	12 weeks
Part I: Trough concentration (Ctrough) of VAD044	Trough concentration (Ctrough) of VAD044	12 weeks
Part I: Pharmacodynamics (PD) of VAD044	PRP assay to measure the levels of pAKT in the blood in a subset of patients	12 weeks
Part II: Change in The number of Epistaxis episodes	The number of Epistaxis episodes	24 months
Part II: Change in Epistaxis duration	Epistaxis duration	24 months
Part II: Change in Epistaxis flow intensity	Epistaxis flow intensity	24 months
Part II: Change in Epistaxis Severity Score (ESS)	ESS used to evaluate the current severity of HHT patient nosebleeds (typically in the last three months) and can help health care providers to evaluate how a patient is responding to treatment. This score ranges from 0-10 and is automatically calculated after answering six simple questions. The higher the score the more severe.	24 months
Part II: Change in Haemoglobin	Haemoglobin	24 months
Part II: Change in Ferritin	Ferritin	24 months
Part II: Change in Transferrin saturation level	Transferrin saturation level	24 months
Part II: Change in Iron supplementation needs	Iron supplementation needs	24 months
Part II: Change in blood tranfusions requirements	blood tranfusions requirements	24 months
Part II: 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.	24 months

Collaborators and Investigators

• Sponsor: Vaderis Therapeutics AG
• Investigators: Study Director: Damien Picard, Vaderis Therapeutics AG

Publications and helpful links

General Publications

• Al-Samkari H, Hessels J, Riera-Mestre A, Dupuis-Girod S, Van Zele T, Gomez Del Olmo V, Hodges PG, Torres-Iglesias R, Berte R, Saint-Mezard P, Lazar H, Benedict N, Barker D, Bernasconi C, Picard D, Buscarini E, Mager HJ. Engasertib versus Placebo for Bleeding in Hereditary Hemorrhagic Telangiectasia. N Engl J Med. 2025 Nov 27;393(21):2131-2141. doi: 10.1056/NEJMoa2504411.

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: May 10, 2022
• First Submitted That Met QC Criteria: June 1, 2022
• First Posted (Actual): June 6, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Arteriovenous Malformations; Osler-Weber-Rendu disease
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hematologic Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Hemostatic Disorders; Hemorrhagic Disorders; Vascular Malformations; Telangiectasis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Telangiectasia, Hereditary Hemorrhagic; Arteriovenous Malformations
• Other Study ID Numbers: VAD044C002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No