Von Willebrand Disease (VWD), Type 2
Conditions
Keywords
von Willebrand's disease, thrombocytopenia, bleeding, placebo
Brief summary
This randomized clinical trial with a cross-over design is being conducted at the Department of Clinical Pharmacology at the Medical University of Vienna, and a total of 4-6 patients with type 2B von Willebrand disease (VWD) will participate. The main purpose of this clinical trial is to investigate the efficacy and safety of BT200, a new drug for thrombocytopenic patients with type 2B von Willebrand disease (VWD). Based on previous studies, we expect that this drug will inhibit the breakdown of von Willebrand factor (VWF) in small doses, leading to an increase in von Willebrand factor (VWF), platelet count, and factor VIII. This should also lead to a reduced tendency to bleed. This study will begin with an observation phase and will then proceed in two periods of approximately 64 days each: Placebo or BT200 will be administered subcutaneously at a dose of 12 mg on the first day of the study. After that, patients will self-administer the drug at a dose of 6 mg (0.4 mL) or placebo once a week for another 4 weeks starting the following week (a total of 4 times over a period of 4 weeks). During this time, they will be asked to come to our clinic for a follow-up visit. After a washout phase lasting several weeks, during which patients do not receive the study drug/placebo but are asked to record any bleeding events, the second period begins on day 64: BT200 or placebo is administered again, depending on what the patients received in the first period. Patients therefore receive the study drug for 4 weeks and placebo for 4 weeks; which is administered when is randomized; a follow-up examination also takes place during this period. At the end of the second period, there is another washout phase lasting several weeks. On day 127, the final examination takes place at the clinic, after which patients have the opportunity to participate in an extension study (to be amended).
Interventions
DRUGBT200
Aptamer directed against the A1 domain of von Willebrand factor
DRUGPlacebo
Placebo for BT200
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
placebo is non-distinguishable from verum based on physicochemical properties (colourless fluid)
Intervention model description
randomized, controlled, double blind, crossover study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥18 years old 2. Type 2B VWD with thrombocytopenia and a recent bleeding history (e.g. recurrent haematomas) 3. Able to comprehend and to give informed consent 4. Able to cooperate with the Investigator, to comply with the requirements of the study, and to complete the full sequence of protocol-related procedures
Exclusion criteria
1. Clinically significant medical history or ongoing chronic illness that would jeopardise the safety of the patient or compromise the quality of the data derived from his/her participation in this study 2. History of significant drug allergy or anaphylactic reactions 3. Substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the Investigator for the patient to be able to comply fully with study procedures 4. Use of medication during 2 weeks before the start of the study, which in the judgment of the Investigator may adversely affect the patient's welfare or the integrity of the study's results 5. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days or 5 elimination half-lives (whichever is longer) prior to treatment start
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Co-Primary Endpoint Clinically evident bleeding | During the five-week Treatment Phase compared with the five-week Control Phase | number of clinically evident bleedings |
| Primary Outcome measure Platelet Counts | During the five-week Treatment Phase compared with the five-week Control Phase | Platelet Counts |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| VWF activity collagen binding | During the five-week Treatment Phase compared with the five-week Control Phase | Activity of VWF quantified with a collagen binding assay |
| VWF:ristocetin co-factor activity | During the five-week Treatment Phase compared with the five-week Control Phase | Activity of VWF quantified with a ristocetin co-factor assay |
| Enzyme-linked immunosorbent assay (ELISA) for unbound VWF-A1 domain (REAADS® ) | During the five-week Treatment Phase compared with the five-week Control Phase | Concentration of unbound VWF-A1 domain quantified by Enzyme-linked immunosorbent assay (ELISA) (REAADS® ) |
| Platelet function under high shear rates | During the five-week Treatment Phase compared with the five-week Control Phase | Platelet Function Analyzer |
| von Willebrand factor antigen | During the five-week Treatment Phase compared with the five-week Control Phase | Concentration of von Willebrand factor antigen quantified by Enzyme-linked immunoassay |
| Serious, drug-related AEs | During the five-week Treatment Phase compared with the five-week Control Phase | Serious, drug-related AEs |
| Premature terminations due to drug-related AEs | During the five-week Treatment Phase compared with the five-week Control Phase | Number of participants who premature terminate treatment due to drug-related AEs |
| Adverse events indicative of BT200 toxicity | During the five-week Treatment Phase compared with the five-week Control Phase | Patterns of serious or non-serious, drug-related AEs, and/or clinically relevant laboratory abnormalities, vital signs, or physical findings suggestive of one or more specific target organs for toxicity of BT200 |
| BT200 plasma concentrations | During the five-week Treatment Phase compared with the five-week Control Phase | plasma concentrations of BT200 |
| von Willebrand factor activity | During the five-week Treatment Phase compared with the five-week Control Phase | von Willebrand factor activity quantified by Gp1bM assay |
Countries
Austria
Contacts
Primary ContactChristian Schörgenhofer, Principal Investigator, MD, PHD
Backup ContactBernd Jilma, Subinvestigator, MD
Outcome results
None listed