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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 30 mg | Experimental | 30 mg VAD044 |
|
| 40 mg | Experimental | 40 mg VAD044 |
|
| Placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VAD044 Part I | Drug | capsules to be taken once daily for 12 weeks |
|
| 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 |
| 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 |
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For Part I of the study:
Inclusion Criteria:
Exclusion Criteria:
Fort Part II of the study:
Inclusion Criteria:
Exclusion Criteria:
- Same as in Part I.
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| Name | Affiliation | Role |
|---|---|---|
| Damien Picard | Vaderis Therapeutics AG | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States | ||
| Universitair Ziekenhuis Gent |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41297007 | Result | 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. |
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| ID | Term |
|---|---|
| D013683 | Telangiectasia, Hereditary Hemorrhagic |
| D001165 | Arteriovenous Malformations |
| ID | Term |
|---|---|
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D013684 | Telangiectasis |
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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
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| VAD044 Part II | Drug | capsules to be taken once daily for 36 months |
|
|
| 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 |
| Ghent |
| Belgium |
| Hospices Civils de Lyon | Lyon | France |
| Ospedale Maggiore di Crema | Crema | Italy |
| St. Antonius Hospital | Nieuwegein | Netherlands |
| Hospital Universiati De Bellvitge | Barcelona | Spain |
| Hospital Universitario Ramón y Cajal | Madrid | Spain |
| D006474 |
| Hemorrhagic Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D054079 | Vascular Malformations |
| D018376 | Cardiovascular Abnormalities |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |