Clinical trial NCT05406362: Assess Safety and Efficacy of VAD044 in HHT Patients
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hereditary Hemorrhagic Telangiectasia (HHT)
Keywords: Osler-Weber-Rendu disease
Arteriovenous Malformations
Lead sponsor: Vaderis Therapeutics AG
Sponsor class: INDUSTRY
First posted: 2022-06-06
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.

Eligibility 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

Exclusion Criteria:

- Same as in Part I.

Primary outcomes:
measure: Part I: Safety and Tolerability
timeFrame: 12 weeks
measure: Part II: Safety and Tolerability
timeFrame: 12 months
Secondary outcomes:
measure: Part I: Change in Epistaxis episodes
timeFrame: 12 weeks
measure: Part I: Change in Epistaxis duration
timeFrame: 12 weeks
measure: Part I: Change in Epistaxis intensity
timeFrame: 12 weeks
measure: Part I: Change in Epistaxis Severity Score (ESS)
timeFrame: 12 weeks
measure: Part I: Change in Haemoglobin
timeFrame: 12 weeks
measure: Part I: Change Ferritin
timeFrame: 12 weeks
measure: Part I: Change in blood Transferrin saturation level
timeFrame: 12 weeks
measure: Part I: Change in Iron supplementation needs
timeFrame: 12 weeks
measure: Part I: Change Blood tranfusions requirements
timeFrame: 12 weeks
measure: Part I: Change in the Nasal Outcome for Epistaxis in Hereditary Hemorrhagic Telangiectasia score
timeFrame: 12 weeks
measure: Part I: Quality of Life Scale SF-12
timeFrame: 12 weeks
measure: Part I: Plasma concentration of VAD044
timeFrame: 12 weeks
measure: Part I: Maximum concentration (Cmax) of VAD04
timeFrame: 12 weeks
measure: Part I: Time of maximum concentration (Tmax) of VAD044
timeFrame: 12 weeks
measure: Part I: Area under the curve (exposure to drug) during 24 hours (AUC0-24h) of VAD044
timeFrame: 12 weeks
measure: Part I: Trough concentration (Ctrough) of VAD044
timeFrame: 12 weeks
measure: Part I: Pharmacodynamics (PD) of VAD044
timeFrame: 12 weeks
measure: Part II: Change in The number of Epistaxis episodes
timeFrame: 12 months
measure: Part II: Change in Epistaxis duration
timeFrame: 12 months
measure: Part II: Change in Epistaxis flow intensity
timeFrame: 12 months
measure: Part II: Change in Epistaxis Severity Score (ESS)
timeFrame: 12 months
measure: Part II: Change in Haemoglobin
timeFrame: 12 months
measure: Part II: Change in Ferritin
timeFrame: 12 months
measure: Part II: Change in Transferrin saturation level
timeFrame: 12 months
measure: Part II: Change in Iron supplementation needs
timeFrame: 12 months
measure: Part II: Change in blood tranfusions requirements
timeFrame: 12 months
measure: Part II: Quality of Life Scale SF-12
timeFrame: 12 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Crema
country: Italy
facility: Ospedale Maggiore di Crema
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
city: Barcelona
country: Spain
facility: Hospital Universiati De Bellvitge
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
Study officials:
affiliation: Vaderis Therapeutics AG
name: Damien Picard
role: STUDY_DIRECTOR
References: