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

Primary Purpose

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

Status

Completed

Phase

Phase 1

Locations

Austria

Study Type

Interventional

Intervention

BT200

Desmopressin

Placebo

About this trial

This is an interventional treatment trial for Cerebrovascular Stroke focused on measuring Secondary Stroke Prevention

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy male or female volunteers, age ≥ 18 years old at screening
If female, must be post-menopausal or status post hysterectomy
Able to comprehend and to give informed consent
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:

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
Clinically relevant abnormal findings on physical examination or clinically relevant laboratory abnormalities
History of infusion hypersensitivity reactions, significant drug allergy, or anaphylactic reactions
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
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
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

Sites / Locations

Medical University of Vienna

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm 15

Arm 16

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Arm Label

BT200 0.18mg

BT200 0.6mg

BT200 1.8mg

BT200 6.0mg

BT200 12.0mg

BT200 24.0mg

BT200 24.0mg rep

Placebo SAD

BT200 loading dose 24.0mg, maintenance doses of 12.0 mg

BT200 loading doses 48.0mg, maintenance doses of 24.0 mg

Placebo MAD

BT200 48.0mg + desmopressin challenge

Placebo + desmopressin challenge dose

Placebo infusion

BT200 36.0mg

BT200 48.0 mg

Arm Description

Subjects will receive a single subcutaneous dose of BT200 0.18mg

Subjects will receive a single subcutaneous dose of BT200 0.6mg

Subjects will receive a single subcutaneous dose of BT200 1.8mg

Subjects will receive a single subcutaneous dose of BT200 6.0mg

Subjects will receive a single subcutaneous dose of BT200 12.0mg

Subjects will receive a single subcutaneous dose of BT200 24.0mg

Subjects will receive a single subcutaneous (SC) dose of BT200 24.0mg by gradual SC infusion

Subjects will receive a single subcutaneous dose of placebo

Subjects will receive an initial subcutaneous loading doses of BT200 24.0mg followed by 4 weekly (every 7 days) maintenance doses of BT200 12.0mg

Subjects will receive an initial subcutaneous loading dose of BT200 48mg followed by 4 weekly (every 7 days) maintenance doses of BT200 24mg

Subjects will receive an initial subcutaneous loading dose of Placebo followed by 4 weekly (every 7 days) maintenance doses of placebo

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

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

Subjects will receive a single IV dose of placebo administered over 24 hours

Subjects will receive a single subcutaneous (SC) dose of BT200 36.0mg by gradual SC infusion

Subjects will receive a single subcutaneous dose (SC) of BT200 48.0mg by gradual SC infusion

Outcomes

Primary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Secondary Outcome Measures

Measured concentration of BT200 at serial time points

Measured Area Under the Curve (AUC)

Maximum Plasma Concentration (Cmax)

Time to maximum plasma concentration (Tmax)

Full Information

NCT ID

NCT04103034

First Posted

September 19, 2019

Last Updated

April 7, 2022

Sponsor

Band Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT04103034

Brief Title

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

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

October 7, 2019 (Actual)

Primary Completion Date

September 14, 2020 (Actual)

Study Completion Date

September 14, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Band Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

Secondary Stroke Prevention

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

112 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BT200 0.18mg

Arm Type

Experimental

Arm Description

Subjects will receive a single subcutaneous dose of BT200 0.18mg

Arm Title

BT200 0.6mg

Arm Type

Experimental

Arm Description

Subjects will receive a single subcutaneous dose of BT200 0.6mg

Arm Title

BT200 1.8mg

Arm Type

Experimental

Arm Description

Subjects will receive a single subcutaneous dose of BT200 1.8mg

Arm Title

BT200 6.0mg

Arm Type

Experimental

Arm Description

Subjects will receive a single subcutaneous dose of BT200 6.0mg

Arm Title

BT200 12.0mg

Arm Type

Experimental

Arm Description

Subjects will receive a single subcutaneous dose of BT200 12.0mg

Arm Title

BT200 24.0mg

Arm Type

Experimental

Arm Description

Subjects will receive a single subcutaneous dose of BT200 24.0mg

Arm Title

BT200 24.0mg rep

Arm Type

Experimental

Arm Description

Subjects will receive a single subcutaneous (SC) dose of BT200 24.0mg by gradual SC infusion

Arm Title

Placebo SAD

Arm Type

Placebo Comparator

Arm Description

Subjects will receive a single subcutaneous dose of placebo

Arm Title

BT200 loading dose 24.0mg, maintenance doses of 12.0 mg

Arm Type

Experimental

Arm Description

Subjects will receive an initial subcutaneous loading doses of BT200 24.0mg followed by 4 weekly (every 7 days) maintenance doses of BT200 12.0mg

Arm Title

BT200 loading doses 48.0mg, maintenance doses of 24.0 mg

Arm Type

Experimental

Arm Description

Subjects will receive an initial subcutaneous loading dose of BT200 48mg followed by 4 weekly (every 7 days) maintenance doses of BT200 24mg

Arm Title

Placebo MAD

Arm Type

Placebo Comparator

Arm Description

Subjects will receive an initial subcutaneous loading dose of Placebo followed by 4 weekly (every 7 days) maintenance doses of placebo

Arm Title

BT200 48.0mg + desmopressin challenge

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo + desmopressin challenge dose

Arm Type

Placebo Comparator

Arm Description

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

Arm Title

Placebo infusion

Arm Type

Placebo Comparator

Arm Description

Subjects will receive a single IV dose of placebo administered over 24 hours

Arm Title

BT200 36.0mg

Arm Type

Experimental

Arm Description

Subjects will receive a single subcutaneous (SC) dose of BT200 36.0mg by gradual SC infusion

Arm Title

BT200 48.0 mg

Arm Type

Experimental

Arm Description

Subjects will receive a single subcutaneous dose (SC) of BT200 48.0mg by gradual SC infusion

Intervention Type

Drug

Intervention Name(s)

BT200

Intervention Description

BT200 is a PEGylated synthetic RNA oligonucleotide

Intervention Type

Drug

Intervention Name(s)

Desmopressin

Other Intervention Name(s)

MINIRIN® Injection

Intervention Description

Sterile solution for injection

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Sterile saline for injection

Primary Outcome Measure Information:

Title

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Time Frame

Baseline through 8 weeks after dosing

Secondary Outcome Measure Information:

Title

Measured concentration of BT200 at serial time points

Time Frame

Baseline through 8 weeks after dosing

Title

Measured Area Under the Curve (AUC)

Time Frame

Baseline through 8 weeks after dosing

Title

Maximum Plasma Concentration (Cmax)

Time Frame

Baseline through 8 weeks after dosing

Title

Time to maximum plasma concentration (Tmax)

Time Frame

Baseline through 8 weeks after dosing

Other Pre-specified Outcome Measures:

Title

Immunogenicity of BT200

Description

Evaluate the presence of anti-drug-antibodies against BT200

Time Frame

Baseline through 8 weeks after dosing

Title

Assess VWF activity using ELISA for free VWF A1 Domains

Time Frame

Baseline through 8 weeks after dosing

Title

Assess VWF function using Platelet Function Analyzer-100

Time Frame

Baseline through 8 weeks after dosing

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy male or female volunteers, age ≥ 18 years old at screening If female, must be post-menopausal or status post hysterectomy Able to comprehend and to give informed consent 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: 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 Clinically relevant abnormal findings on physical examination or clinically relevant laboratory abnormalities History of infusion hypersensitivity reactions, significant drug allergy, or anaphylactic reactions 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 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

James C Gilbert, MD

Organizational Affiliation

Band Therapeutics

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Ulla Derhaschnig, MD

Organizational Affiliation

Medical University of Vienna

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical University of Vienna

City

Vienna

ZIP/Postal Code

1090

Country

Austria

12. IPD Sharing Statement

Citations:

PubMed Identifier

29847840

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.

Results Reference

background

PubMed Identifier

34818873

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.

Results Reference

result

PubMed Identifier

34818875

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.

Results Reference

result

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

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