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

Band Therapeutics

Status and phase: Completed; Phase 1

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

Treatments: Drug: BT200; Drug: Placebo; Drug: Desmopressin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04103034

BT200-01

Details and patient eligibility

About

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.

Enrollment: 112 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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112 participants in 18 patient groups, including a placebo group

BT200 0.18mg

Experimental group

Description:

Subjects will receive a single subcutaneous dose of BT200 0.18mg

Treatment:

Drug: BT200

BT200 0.6mg

Experimental group

Description:

Subjects will receive a single subcutaneous dose of BT200 0.6mg

Treatment:

Drug: BT200

BT200 1.8mg

Experimental group

Description:

Subjects will receive a single subcutaneous dose of BT200 1.8mg

Treatment:

Drug: BT200

BT200 6.0mg

Experimental group

Description:

Subjects will receive a single subcutaneous dose of BT200 6.0mg

Treatment:

Drug: BT200

BT200 12.0mg

Experimental group

Description:

Subjects will receive a single subcutaneous dose of BT200 12.0mg

Treatment:

Drug: BT200

BT200 24.0mg

Experimental group

Description:

Subjects will receive a single subcutaneous dose of BT200 24.0mg

Treatment:

Drug: BT200

BT200 24.0mg rep

Experimental group

Description:

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

Treatment:

Drug: BT200

Placebo SAD

Placebo Comparator group

Description:

Subjects will receive a single subcutaneous dose of placebo

Treatment:

Drug: Placebo

BT200 loading dose 12.0mg, maintenance doses of 12.0 mg

Experimental group

Description:

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

Treatment:

Drug: BT200

BT200 loading doses 24.0mg, maintenance doses of 24.0 mg

Experimental group

Description:

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

Treatment:

Drug: BT200

Placebo MAD

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

BT200 48.0mg + desmopressin challenge

Experimental group

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

Treatment:

Drug: Desmopressin

Drug: BT200

Placebo + desmopressin challenge dose

Placebo Comparator group

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

Treatment:

Drug: Desmopressin

Drug: BT200

Placebo infusion

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

BT200 36.0mg

Experimental group

Description:

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

Treatment:

Drug: BT200

BT200 48.0 mg

Experimental group

Description:

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

Treatment:

Drug: BT200

BT200 18.0 mg

Experimental group

Description:

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

Treatment:

Drug: BT200

BT200 24mg IV infusion

Experimental group

Description:

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

Treatment:

Drug: BT200