Trial · Interventional

CompletedPhase 1Results postedRegistry data

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

NCTNCT04103034Other idBT200-01

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 1
Enrollment: 112 participants (actual)
Sponsor: Band Therapeutics · Industry
Design: Randomized · Triple masking
Countries: 1 country
Austria
Start: 7 Oct 2019
Primary completion: 14 Sept 2020
Completion: 14 Sept 2020
First posted: 25 Sept 2019
Last update posted: 18 Mar 2024
Conditions: Cerebrovascular Stroke · Large-Artery Atherosclerosis (Embolus/Thrombosis) · Intracranial Arteriosclerosis

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

201920202021

Ph 1
A SAD/MAD Study of Safety, Tolerability and Pharmacologic Activity of BT200 in Normal Volunteers
NCT04103034
7 Oct 2019 to 14 Sept 2020

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

BT200Drug
DesmopressinDrug
PlaceboDrug

Arms18

Experimental
BT200 0.18mg
Subjects will receive a single subcutaneous dose of BT200 0.18mg
Experimental
BT200 0.6mg
Subjects will receive a single subcutaneous dose of BT200 0.6mg
Experimental
BT200 1.8mg
Subjects will receive a single subcutaneous dose of BT200 1.8mg
Experimental
BT200 6.0mg
Subjects will receive a single subcutaneous dose of BT200 6.0mg
Experimental
BT200 12.0mg
Subjects will receive a single subcutaneous dose of BT200 12.0mg
Experimental
BT200 24.0mg
Subjects will receive a single subcutaneous dose of BT200 24.0mg
Experimental
BT200 24.0mg rep
Subjects will receive a single subcutaneous (SC) dose of BT200 24.0mg by gradual SC infusion
Placebo comparator
Placebo SAD
Subjects will receive a single subcutaneous dose of placebo
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
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
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
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
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
Placebo comparator
Placebo infusion
Subjects will receive a single IV dose of placebo administered over 24 hours
Experimental
BT200 36.0mg
Subjects will receive a single subcutaneous (SC) dose of BT200 36.0mg by gradual SC infusion
Experimental
BT200 48.0 mg
Subjects will receive a single subcutaneous dose (SC) of BT200 48.0mg by gradual SC infusion
Experimental
BT200 18.0 mg
Subjects will receive a single subcutaneous (SC) dose of BT200 18.0mg by gradual SC infusion
Experimental
BT200 24mg IV infusion
Subjects will receive a single IV dose of BT200 24mg administered over 24 hours

Primary outcomes1

Outcomes the sponsor listed as primary.

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

Secondary outcomes(3)

Measured Area Under the Curve (AUC)
Time frame · Baseline through 8 weeks after dosing up to 56 days
Registry description
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)
Time frame · Baseline through 8 weeks after dosing up to 56 days
Registry description
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)
Time frame · Baseline through 8 weeks after dosing up to 56 days
Registry description
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

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· Baseline through 8 weeks after dosing up to 56 days

Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0

Group	Value (Participants)
BT200 0.18mg	0
BT200 0.6mg	1
BT200 1.8mg	0
BT200 6.0mg	1
BT200 12.0mg	1
BT200 24.0mg	0
BT200 24.0mg Rep	1
Placebo SAD	2
BT200 Loading Dose 12.0mg, Maintenance Doses of 12.0 mg	4
BT200 Loading Doses 24.0mg, Maintenance Doses of 24.0 mg	3
Placebo MAD	3
BT200 48.0mg + Desmopressin Challenge	3
Placebo + Desmopressin Challenge Dose	0
Placebo Infusion	0
BT200 36.0mg	0
BT200 48.0 mg	3
BT200 18.0 mg	2
BT200 24mg IV Infusion	0

Secondary and other outcome results(3)

Secondary outcomeMean· Baseline through 8 weeks after dosing up to 56 days

Measured Area Under the Curve (AUC)

Group	Value (h*ug/mL)	Spread
BT200 0.18mg	1.159	0.72594
BT200 0.6mg	5.405	2.1113
BT200 1.8mg	11.50	6.5663
BT200 6.0mg	64.39	22.534
BT200 12.0mg	161.6	43.427
BT200 24.0mg	259.5	99.216
BT200 24.0mg Rep	265.3	59.127
BT200 Loading Dose 24.0mg, Maintenance Doses of 12.0 mg	409.4	32.347
BT200 Loading Doses 48.0mg, Maintenance Doses of 24.0 mg	806.8	187.25
BT200 48.0mg + Desmopressin Challenge	675.9	204.80
BT200 36.0mg	366.2	78.610
BT200 48.0 mg	638.8	90.467
BT200 18.0 mg	220.3	64.58
BT200 24mg IV Infusion	555.4	126.99

Secondary outcomeMean· Baseline through 8 weeks after dosing up to 56 days

Maximum Plasma Concentration (Cmax)

Group	Value (ug/mL)	Spread
BT200 0.18mg	0.01025	0.0055459
BT200 0.6mg	0.04688	0.018522
BT200 1.8mg	0.09432	0.035964
BT200 6.0mg	0.5087	0.18430
BT200 12.0mg	1.258	0.35540
BT200 24.0mg	2.092	0.07627
BT200 24.0mg Rep	2.080	0.46217
BT200 Loading Dose 24.0mg, Maintenance Doses of 12.0 mg	3.013	0.25185
BT200 Loading Doses 48.0mg, Maintenance Doses of 24.0 mg	5.823	1.3606
BT200 48.0mg + Desmopressin Challenge	6.598	2.6719
BT200 36.0mg	3.248	11724
BT200 48.0 mg	5.525	0.95429
BT200 18.0 mg	1.742	0.49545
BT200 24mg IV Infusion	5.037	1.3953

Secondary outcomeMean· Baseline through 8 weeks after dosing up to 56 days

Time to Maximum Plasma Concentration (Tmax)

Group	Value ((h))	Spread
BT200 0.18mg	111.867	111.7018
BT200 0.6mg	80.433	20.2385
BT200 1.8mg	72.364	22.0757
BT200 6.0mg	100.239	53.4433
BT200 12.0mg	72.761	21.4536
BT200 24.0mg	100.247	38.5146
BT200 24.0mg Rep	88.517	19.7697
BT200 Loading Dose 24.0mg, Maintenance Doses of 12.0 mg	29.892	25.8845
BT200 Loading Doses 48.0mg, Maintenance Doses of 24.0 mg	12.811	17.9877
BT200 48.0mg + Desmopressin Challenge	105.919	18.9321
BT200 36.0mg	139.647	46.6683
BT200 48.0 mg	107.892	113.4475
BT200 18.0 mg	100.247	38.5146
BT200 24mg IV Infusion	23.864	0.2642

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
BT200 0.18mgSubjects will receive a single subcutaneous dose of BT200 0.18mg BT200: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	0 / 6	4 / 6
BT200 0.6mgSubjects will receive a single subcutaneous dose of BT200 0.6mg BT200: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	0 / 6	3 / 6
BT200 1.8mgSubjects will receive a single subcutaneous dose of BT200 1.8mg BT200: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	0 / 6	4 / 6
BT200 6.0mgSubjects will receive a single subcutaneous dose of BT200 6.0mg BT200: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	0 / 6	4 / 6
BT200 12.0mgSubjects will receive a single subcutaneous dose of BT200 12.0mg BT200: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	0 / 6	5 / 6
BT200 24.0mgSubjects will receive a single subcutaneous dose of BT200 24.0mg BT200: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	0 / 6	6 / 6
BT200 24.0mg RepSubjects will receive a single subcutaneous (SC) dose of BT200 24.0mg by gradual SC infusion BT200: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	1 / 6	5 / 6
Placebo SADSubjects will receive a single subcutaneous dose of placebo Placebo: Sterile saline for injection	0 / 20	1 / 20	16 / 20
BT200 Loading Dose 12.0mg, Maintenance Doses of 12.0 mgSubjects 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: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	0 / 6	6 / 6
BT200 Loading Doses 24.0mg, Maintenance Doses of 24.0 mgSubjects will receive an initial subcutaneous loading dose of BT200 24mg followed by 4 weekly (every 7 days) maintenance doses of BT200 24mg BT200: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	1 / 6	6 / 6
Placebo MADSubjects will receive an initial subcutaneous loading dose of Placebo followed by 4 weekly (every 7 days) maintenance doses of placebo Placebo: Sterile saline for injection	0 / 4	0 / 4	4 / 4
BT200 48.0mg + Desmopressin ChallengeSubjects 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: BT200 is a PEGylated synthetic RNA oligonucleotide Desmopressin: Sterile solution for injection	0 / 6	0 / 6	5 / 6
Placebo + Desmopressin Challenge DoseSubjects 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: BT200 is a PEGylated synthetic RNA oligonucleotide Desmopressin: Sterile solution for injection	0 / 2	0 / 2	1 / 2
Placebo InfusionSubjects will receive a single IV dose of placebo administered over 24 hours Placebo: Sterile saline for injection	0 / 2	0 / 2	1 / 2
BT200 36.0mgSubjects will receive a single subcutaneous (SC) dose of BT200 36.0mg by gradual SC infusion BT200: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	0 / 6	4 / 6
BT200 48.0 mgSubjects will receive a single subcutaneous dose (SC) of BT200 48.0mg by gradual SC infusion BT200: BT200 is a PEGylated synthetic RNA oligonucleotide	0 / 6	1 / 6	4 / 6
BT200 18.0 mgSubjects will receive a single subcutaneous dose of BT200 18.o mg	0 / 6	0 / 6	5 / 6
BT200 24mg IV InfusionSubjects will receive a single IV dose of BT200 24mg administered over 24 hours	0 / 6	0 / 6	4 / 6

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

ResultKovacevic 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
ResultDenis 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

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years
Healthy volunteers: Accepted

Inclusion and exclusion criteria, as posted

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

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