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

Phase 1

Completed

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

• Registration Number: NCT04103034
• Lead Sponsor: Band Therapeutics

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-19
• Study First Submitted QC: 2019-09-23
• Study First Posted: 2019-09-25
• Study Start: 2019-10-07
• Primary Completion: 2020-09-14
• Study Completion: 2020-09-14
• Results First Submitted: 2022-10-06
• Status Verified: 2023-09
• Results First Submitted QC: 2023-09-06
• Last Update Submitted: 2023-09-06
• Results First Posted: 2024-03-18
• Last Update Posted: 2024-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 112

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo infusion	Placebo	Subjects will receive a single IV dose of placebo administered over 24 hours
Placebo SAD	Placebo	Subjects will receive a single subcutaneous dose of placebo
Placebo MAD	Placebo	Subjects will receive an initial subcutaneous loading dose of Placebo followed by 4 weekly (every 7 days) maintenance doses of placebo
BT200 0.6mg	BT200	Subjects will receive a single subcutaneous dose of BT200 0.6mg
BT200 6.0mg	BT200	Subjects will receive a single subcutaneous dose of BT200 6.0mg
BT200 loading dose 12.0mg, maintenance doses of 12.0 mg	BT200	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
BT200 48.0mg + desmopressin challenge	Desmopressin	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
Placebo + desmopressin challenge dose	Desmopressin	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
BT200 48.0 mg	BT200	Subjects will receive a single subcutaneous dose (SC) of BT200 48.0mg by gradual SC infusion
BT200 24mg IV infusion	BT200	Subjects will receive a single IV dose of BT200 24mg administered over 24 hours
BT200 0.18mg	BT200	Subjects will receive a single subcutaneous dose of BT200 0.18mg
BT200 1.8mg	BT200	Subjects will receive a single subcutaneous dose of BT200 1.8mg
BT200 12.0mg	BT200	Subjects will receive a single subcutaneous dose of BT200 12.0mg
BT200 24.0mg	BT200	Subjects will receive a single subcutaneous dose of BT200 24.0mg
BT200 24.0mg rep	BT200	Subjects will receive a single subcutaneous (SC) dose of BT200 24.0mg by gradual SC infusion
BT200 loading doses 24.0mg, maintenance doses of 24.0 mg	BT200	Subjects will receive an initial subcutaneous loading dose of BT200 24mg followed by 4 weekly (every 7 days) maintenance doses of BT200 24mg
Placebo + desmopressin challenge dose	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
BT200 48.0mg + desmopressin challenge	BT200	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
BT200 36.0mg	BT200	Subjects will receive a single subcutaneous (SC) dose of BT200 36.0mg by gradual SC infusion
BT200 18.0 mg	BT200	Subjects will receive a single subcutaneous (SC) dose of BT200 18.0mg by gradual SC infusion

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0	Baseline through 8 weeks after dosing up to 56 days	Any AE or bleeding event related to study treatment

Secondary Outcome Measures

Name	Time	Method
Measured Area Under the Curve (AUC)	Baseline through 8 weeks after dosing up to 56 days	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
Maximum Plasma Concentration (Cmax)	Baseline through 8 weeks after dosing up to 56 days	Maximum plasma Concentration measured at pre-dose, 0.5h, 1h, 4h, 8h,14h, 24h, 48h, 72h, 96h, 168h, 14d, 21d, 28d, 42d, 56d
Time to Maximum Plasma Concentration (Tmax)	Baseline through 8 weeks after dosing up to 56 days	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

Trial Locations

Locations (1)

Medical University of Vienna; 🇦🇹 Vienna, Austria