A SAD/MAD Study of Safety, Tolerability and Pharmacologic Activity of BT200 in Normal Volunteers

Cerebrovascular Stroke Clinical Trial

Official title:

A Single/Multiple Ascending Dose Phase 1 Study of the Safety, Tolerability and Pharmacologic Activity of BT200 in Normal Human Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04103034
• Other study ID #: BT200-01
• Status: Completed
• Phase: Phase 1
• Start date: October 7, 2019
• Est. completion date: September 14, 2020

Study information

• Verified date: September 2023
• Source: Band Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: September 14, 2020
• Est. primary completion date: September 14, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arteriosclerosis
• Atherosclerosis
• Cerebrovascular Stroke
• Intracranial Arteriosclerosis
• Large-Artery Atherosclerosis (Embolus/Thrombosis)
• Stroke
• Thrombosis

Intervention

Drug:
• BT200
BT200 is a PEGylated synthetic RNA oligonucleotide
• Desmopressin
Sterile solution for injection
• Placebo
Sterile saline for injection

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Band Therapeutics

Country where clinical trial is conducted

Austria, 

References & Publications (3)

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. — View 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	Any AE or bleeding event related to study treatment	Baseline through 8 weeks after dosing up to 56 days
Secondary	Measured Area Under the Curve (AUC)	Measured Area Under the Curve at timepoints pre-dose, 0.5h, 1h, 4h, 8h,14h, 24h, 48h, 72h, 96h, 168h, 14d, 21d, 28d, 42d, 56d post dose	Baseline through 8 weeks after dosing up to 56 days
Secondary	Maximum Plasma Concentration (Cmax)	Maximum plasma Concentration measured at pre-dose, 0.5h, 1h, 4h, 8h,14h, 24h, 48h, 72h, 96h, 168h, 14d, 21d, 28d, 42d, 56d	Baseline through 8 weeks after dosing up to 56 days
Secondary	Time to Maximum Plasma Concentration (Tmax)	Time to maximum plasma concentration measured at pre-dose, 0.5h, 1h, 4h, 8h,14h, 24h, 48h, 72h, 96h, 168h, 14d, 21d, 28d, 42d, 56d	Baseline through 8 weeks after dosing up to 56 days