Hereditary Hemorrhagic Telangiectasia (HHT)
Conditions
Keywords
Osler-Weber-Rendu disease, Arteriovenous Malformations
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 36 months.
Interventions
DRUGVAD044 Part I
capsules to be taken once daily for 12 weeks
DRUGVAD044 Part II
capsules to be taken once daily for 36 months
Sponsors
Vaderis Therapeutics AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part I: Safety and Tolerability | 12 weeks | Type and severity of Adverse Events (AEs) |
| Part II: Safety and Tolerability | 36 months | Type and severity of Adverse Events (AEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 24 months | The number of Epistaxis episodes |
| Part II: Change in Epistaxis duration | 24 months | Epistaxis duration |
| Part II: Change in Epistaxis flow intensity | 24 months | Epistaxis flow intensity |
| Part II: Change in Epistaxis Severity Score (ESS) | 24 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 | 24 months | Haemoglobin |
| Part II: Change in Ferritin | 24 months | Ferritin |
| Part II: Change in Transferrin saturation level | 24 months | Transferrin saturation level |
| Part II: Change in Iron supplementation needs | 24 months | Iron supplementation needs |
| Part II: Change in blood tranfusions requirements | 24 months | blood tranfusions requirements |
| Part II: Quality of Life Scale SF-12 | 24 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. |
| Part I: Change in Epistaxis episodes | 12 weeks | The number of Epistaxis episodes |
Countries
Belgium, France, Italy, Netherlands, Spain, United States
Contacts
STUDY_DIRECTORDamien Picard
Vaderis Therapeutics AG
Outcome results
None listed