Clinical trial NCT04103034: A SAD/MAD Study of Safety, Tolerability and Pharmacologic Activity of BT200 in Normal Volunteers
Official title: A Single/Multiple Ascending Dose Phase 1 Study of the Safety, Tolerability and Pharmacologic Activity of BT200 in Normal Human Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cerebrovascular Stroke
Large-Artery Atherosclerosis (Embolus/Thrombosis)
Intracranial Arteriosclerosis
Keywords: Secondary Stroke Prevention
Lead sponsor: Band Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-09-25
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Study BT200-01 is a first in human (FIH) study in male and female normal human volunteers (NHVs) that uses an Integrated Protocol Design. This Phase 1 study will comprise 4 sub-parts: Part A, a single ascending dose (SAD) study; Part B, a multiple ascending dose (MAD) study; Part C, a desmopressin challenge study to explore (i) whether desmopressin could be used as an antidote, and/or (ii) whether desmopressin stimulated vonWillebrand Factor (VWF) release is overcome with increasing BT200 doses; and Part D, a relative bioavailability (BA) study.

The primary objective of this study is to assess the safety and tolerability profile of BT200 in NHVs.


Eligibility criteria: Inclusion Criteria:

1. Healthy male or female volunteers, age ≥ 18 years old at screening
2. If female, must be post-menopausal or status post hysterectomy
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 (including von Willebrand Disease, thrombocytopathy, or any type of bleeding diathesis) or ongoing chronic illness that would jeopardize the safety of the subject or compromise the quality of the data derived from his/her participation in this study
2. Clinically relevant abnormal findings on physical examination or clinically relevant laboratory abnormalities
3. History of infusion hypersensitivity reactions, significant drug allergy, or anaphylactic reactions
4. Substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the Investigator for the subject to be able to comply fully with study procedures
5. Use of medication during 2 weeks before the start of the study, which in the judgment of the Investigator may adversely affect the subject's welfare or the integrity of the study's results
6. 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

Primary outcomes:
measure: Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
timeFrame: Baseline through 8 weeks after dosing up to 56 days
Secondary outcomes:
measure: Measured Area Under the Curve (AUC)
timeFrame: Baseline through 8 weeks after dosing up to 56 days
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Baseline through 8 weeks after dosing up to 56 days
measure: Time to Maximum Plasma Concentration (Tmax)
timeFrame: Baseline through 8 weeks after dosing up to 56 days
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
Study officials:
affiliation: Band Therapeutics
name: James C Gilbert, MD
role: STUDY_DIRECTOR
affiliation: Medical University of Vienna
name: Ulla Derhaschnig, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Buchtele N, Schwameis M, Gilbert JC, Schorgenhofer C, Jilma B. Targeting von Willebrand Factor in Ischaemic Stroke: Focus on Clinical Evidence. Thromb Haemost. 2018 Jun;118(6):959-978. doi: 10.1055/s-0038-1648251. Epub 2018 May 30.
citation: Kovacevic KD, Grafeneder J, Schorgenhofer C, Gelbenegger G, Gager G, Firbas C, Quehenberger P, Jilma-Stohlawetz P, Bileck A, Zhu S, Gilbert JC, Beliveau M, Jilma B, Derhaschnig U. The von Willebrand factor A-1 domain binding aptamer BT200 elevates plasma levels of von Willebrand factor and factor VIII: a first-in-human trial. Haematologica. 2022 Sep 1;107(9):2121-2132. doi: 10.3324/haematol.2021.279948.
citation: Denis CV, Lenting PJ. How to keep the factor VIII/von Willebrand factor complex in the circulation. Haematologica. 2022 Sep 1;107(9):2011-2013. doi: 10.3324/haematol.2021.280222. No abstract available.