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

NCT04103034 | Completed Phase 1 Results DMC

• 1 other identifier: BT200-01
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Secondary Stroke Prevention

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Measured Area Under the Curve (AUC)

  Baseline through 8 weeks after dosing up to 56 days

• Maximum Plasma Concentration (Cmax)

  Baseline through 8 weeks after dosing up to 56 days

• Time to Maximum Plasma Concentration (Tmax)

  Baseline through 8 weeks after dosing up to 56 days

Study Arms (18)

BT200 0.18mg

EXPERIMENTAL

Subjects will receive a single subcutaneous dose of BT200 0.18mg

Drug: BT200

BT200 0.6mg

EXPERIMENTAL

Subjects will receive a single subcutaneous dose of BT200 0.6mg

Drug: BT200

BT200 1.8mg

EXPERIMENTAL

Subjects will receive a single subcutaneous dose of BT200 1.8mg

Drug: BT200

BT200 6.0mg

EXPERIMENTAL

Subjects will receive a single subcutaneous dose of BT200 6.0mg

Drug: BT200

BT200 12.0mg

EXPERIMENTAL

Subjects will receive a single subcutaneous dose of BT200 12.0mg

Drug: BT200

BT200 24.0mg

EXPERIMENTAL

Subjects will receive a single subcutaneous dose of BT200 24.0mg

Drug: BT200

BT200 24.0mg rep

EXPERIMENTAL

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

Drug: BT200

Placebo SAD

PLACEBO COMPARATOR

Subjects will receive a single subcutaneous dose of placebo

Drug: Placebo

BT200 loading dose 12.0mg, maintenance doses of 12.0 mg

EXPERIMENTAL

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 loading doses 24.0mg, maintenance doses of 24.0 mg

EXPERIMENTAL

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

Placebo MAD

PLACEBO COMPARATOR

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

Drug: Placebo

BT200 48.0mg + desmopressin challenge

EXPERIMENTAL

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; Drug: Desmopressin

Placebo + desmopressin challenge dose

PLACEBO COMPARATOR

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; Drug: Desmopressin

Placebo infusion

PLACEBO COMPARATOR

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

Drug: Placebo

BT200 36.0mg

EXPERIMENTAL

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

Drug: BT200

BT200 48.0 mg

EXPERIMENTAL

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

Drug: BT200

BT200 18.0 mg

EXPERIMENTAL

Subjects will receive a single subcutaneous (SC) dose of BT200 18.0mg by gradual SC infusion

Drug: BT200

BT200 24mg IV infusion

EXPERIMENTAL

Subjects will receive a single IV dose of BT200 24mg administered over 24 hours

Drug: BT200

Interventions

BT200 DRUG

BT200 is a PEGylated synthetic RNA oligonucleotide

BT200 0.18mg; BT200 0.6mg; BT200 1.8mg; BT200 12.0mg; BT200 18.0 mg; BT200 24.0mg; BT200 24.0mg rep; BT200 24mg IV infusion; BT200 36.0mg; BT200 48.0 mg; BT200 48.0mg + desmopressin challenge; BT200 6.0mg; BT200 loading dose 12.0mg, maintenance doses of 12.0 mg; BT200 loading doses 24.0mg, maintenance doses of 24.0 mg; Placebo + desmopressin challenge dose

Desmopressin DRUG

Sterile solution for injection

Also known as: MINIRIN® Injection

BT200 48.0mg + desmopressin challenge; Placebo + desmopressin challenge dose

Placebo DRUG

Sterile saline for injection

Placebo MAD; Placebo SAD; Placebo infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Band Therapeutics: lead

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

Location

Related 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.

  PMID: 29847840 BACKGROUND

• 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.

  PMID: 34818873 RESULT

• 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.

  PMID: 34818875 RESULT

MeSH Terms

Conditions

Stroke; Embolism; Thrombosis; Intracranial Arteriosclerosis

Interventions

Deamino Arginine Vasopressin

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Intracranial Arterial Diseases; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Arginine Vasopressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Tia DeFeo-Fraulini
• Organization: Band Therapeutics

tia.defeo-fraulini@bandtherapeutics.com

7819186561

Study Officials

• James C Gilbert, MD

  Band Therapeutics

  STUDY DIRECTOR

• Ulla Derhaschnig, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2019
• First Posted: September 25, 2019
• Study Start: October 7, 2019
• Primary Completion: September 14, 2020
• Study Completion: September 14, 2020
• Last Updated: March 18, 2024
• Results First Posted: March 18, 2024

Record last verified: 2023-09

Locations

AU (1)