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

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

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.

Study Overview

• Status: Completed
• Conditions: Intracranial Arteriosclerosis; Cerebrovascular Stroke; Large-Artery Atherosclerosis (Embolus/Thrombosis)
• Intervention / Treatment: Drug: BT200; Drug: Placebo; Drug: Desmopressin

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

18

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BT200 0.18mg; Subjects will receive a single subcutaneous dose of BT200 0.18mg	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 0.6mg; Subjects will receive a single subcutaneous dose of BT200 0.6mg	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 1.8mg; Subjects will receive a single subcutaneous dose of BT200 1.8mg	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 6.0mg; Subjects will receive a single subcutaneous dose of BT200 6.0mg	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 12.0mg; Subjects will receive a single subcutaneous dose of BT200 12.0mg	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 24.0mg; Subjects will receive a single subcutaneous dose of BT200 24.0mg	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 24.0mg rep; Subjects will receive a single subcutaneous (SC) dose of BT200 24.0mg by gradual SC infusion	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Placebo Comparator: Placebo SAD; Subjects will receive a single subcutaneous dose of placebo	Drug: Placebo; Sterile saline for injection
Placebo Comparator: Placebo MAD; Subjects will receive an initial subcutaneous loading dose of Placebo followed by 4 weekly (every 7 days) maintenance doses of placebo	Drug: Placebo; Sterile saline for injection
Experimental: BT200 48.0mg + desmopressin challenge; Subjects will receive a single subcutaneous dose of BT200 48.0mg followed by IV infusion (over 30 min) of 0.3µg/kg desmopressin administered 24 hours after single dose of BT200	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide; Drug: Desmopressin; Sterile solution for injection; Other Names: MINIRIN® Injection
Placebo Comparator: Placebo + desmopressin challenge dose; Subjects will receive a single subcutaneous dose of placebo followed by IV infusion (over 30 min of 0.3µg/kg desmopressin administered 24 hours after single dose of placebo	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide; Drug: Desmopressin; Sterile solution for injection; Other Names: MINIRIN® Injection
Placebo Comparator: Placebo infusion; Subjects will receive a single IV dose of placebo administered over 24 hours	Drug: Placebo; Sterile saline for injection
Experimental: BT200 36.0mg; Subjects will receive a single subcutaneous (SC) dose of BT200 36.0mg by gradual SC infusion	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 48.0 mg; Subjects will receive a single subcutaneous dose (SC) of BT200 48.0mg by gradual SC infusion	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 loading dose 12.0mg, maintenance doses of 12.0 mg; Subjects will receive an initial subcutaneous loading doses of BT200 12.0mg followed by 4 weekly (every 7 days) maintenance doses of BT200 12.0mg	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 loading doses 24.0mg, maintenance doses of 24.0 mg; Subjects will receive an initial subcutaneous loading dose of BT200 24mg followed by 4 weekly (every 7 days) maintenance doses of BT200 24mg	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 18.0 mg; Subjects will receive a single subcutaneous (SC) dose of BT200 18.0mg by gradual SC infusion	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide
Experimental: BT200 24mg IV infusion; Subjects will receive a single IV dose of BT200 24mg administered over 24 hours	Drug: BT200; BT200 is a PEGylated synthetic RNA oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity of BT200	Evaluate the presence of anti-drug-antibodies against BT200	Baseline through 8 weeks after dosing
Assess VWF activity using ELISA for free VWF A1 Domains		Baseline through 8 weeks after dosing
Assess VWF function using Platelet Function Analyzer-100		Baseline through 8 weeks after dosing

Collaborators and Investigators

• Sponsor: Band Therapeutics
• Investigators: Study Director: James C Gilbert, MD, Band Therapeutics; Principal Investigator: Ulla Derhaschnig, MD, Medical University of Vienna

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2019
• Primary Completion (Actual): September 14, 2020
• Study Completion (Actual): September 14, 2020

Study Registration Dates

• First Submitted: September 19, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Secondary Stroke Prevention
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Embolism and Thrombosis; Intracranial Arterial Diseases; Stroke; Thrombosis; Arteriosclerosis; Atherosclerosis; Intracranial Arteriosclerosis; Physiological Effects of Drugs; Natriuretic Agents; Hemostatics; Coagulants; Antidiuretic Agents; Deamino Arginine Vasopressin
• Other Study ID Numbers: BT200-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No