Assess Safety and Efficacy of VAD044 in HHT Patients
- Conditions
- Hereditary Hemorrhagic Telangiectasia (HHT)
- Interventions
- Drug: VAD044 Part IDrug: VAD044 Part II
- Registration Number
- NCT05406362
- Lead Sponsor
- Vaderis Therapeutics AG
- Brief Summary
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.
- 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 12 months.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 75
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 30 mg VAD044 Part I 30 mg VAD044 30 mg VAD044 Part II 30 mg VAD044 40 mg VAD044 Part I 40 mg VAD044 40 mg VAD044 Part II 40 mg VAD044 Placebo VAD044 Part I Placebo
- Primary Outcome Measures
Name Time Method Part I: Safety and Tolerability 12 weeks Type and severity of Adverse Events (AEs)
Part II: Safety and Tolerability 12 months Type and severity of Adverse Events (AEs)
- Secondary Outcome Measures
Name Time Method Part I: Change in Epistaxis episodes 12 weeks The number of Epistaxis episodes
Part I: Change in Epistaxis duration 12 weeks Epistaxis duration
Part I: Change in Epistaxis intensity 12 weeks Epistaxis flow intensity
Part I: Change in Epistaxis Severity Score (ESS) 12 weeks 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.
Part I: Change in Haemoglobin 12 weeks Haemoglobin
Part I: Change Ferritin 12 weeks Ferritin
Part I: Change in blood Transferrin saturation level 12 weeks Transferrin saturation level
Part I: Change in Iron supplementation needs 12 weeks Iron supplementation needs
Part I: Change Blood tranfusions requirements 12 weeks Blood tranfusions requirements
Part I: Change in the Nasal Outcome for Epistaxis in Hereditary Hemorrhagic Telangiectasia score 12 weeks 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
Part I: Quality of Life Scale SF-12 12 weeks 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.
Part I: Plasma concentration of VAD044 12 weeks Plasma concentration of VAD044
Part I: Maximum concentration (Cmax) of VAD04 12 weeks Maximum concentration (Cmax) of VAD044
Part I: Time of maximum concentration (Tmax) of VAD044 12 weeks Time of maximum concentration (Tmax) of VAD044
Part I: Area under the curve (exposure to drug) during 24 hours (AUC0-24h) of VAD044 12 weeks Area under the curve (exposure to drug) during 24 hours (AUC0-24h) of VAD044
Part I: Trough concentration (Ctrough) of VAD044 12 weeks Trough concentration (Ctrough) of VAD044
Part I: Pharmacodynamics (PD) of VAD044 12 weeks PRP assay to measure the levels of pAKT in the blood in a subset of patients
Part II: Change in The number of Epistaxis episodes 12 months The number of Epistaxis episodes
Part II: Change in Epistaxis duration 12 months Epistaxis duration
Part II: Change in Epistaxis flow intensity 12 months Epistaxis flow intensity
Part II: Change in Epistaxis Severity Score (ESS) 12 months 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.
Part II: Change in Haemoglobin 12 months Haemoglobin
Part II: Change in Ferritin 12 months Ferritin
Part II: Change in Transferrin saturation level 12 months Transferrin saturation level
Part II: Change in Iron supplementation needs 12 months Iron supplementation needs
Part II: Change in blood tranfusions requirements 12 months blood tranfusions requirements
Part II: Quality of Life Scale SF-12 12 months 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.
Trial Locations
- Locations (7)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Universitair Ziekenhuis Gent
🇧🇪Gent, 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