BT200 in Hereditary Bleeding Disorders

Hemophilia A Clinical Trial

Official title:

A Phase 2a Multiple Dose Basket Study of the Safety, Tolerability, and Pharmacologic Activity of BT200 in Patients With Hereditary Bleeding Disorders

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04677803
• Other study ID #: BT200-02
• Status: Completed
• Phase: Phase 2
• Start date: December 14, 2020
• Est. completion date: September 10, 2021

Study information

• Verified date: November 2021
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

BT200 is a PEGylated aptamer that binds to the A1 domain of human von Willebrand factor (VWF). At low doses, BT200 blocks the clearance of VWF antigen (VWF Ag) from the circulation and causes an increase in concentrations of both VWF Ag and Factor VIII (FVIII), but has negligible effect on the activity of either. At higher doses, BT200 blocks clearance of VWF and also inhibits its activity, but still does not inhibit FVIII activity. Therefore, low dose BT200 could potentially be used to correct deficiency of VWF and/or FVIII in patients with hereditary bleeding disorders. This study is designed as a "basket design" pilot study to determine the relevant dose and pharmacological activity of BT200 in such patients.

In this open basket study up to 25 patients with the following congenital blood-clotting disorders are to be included: Patients with hemophilia A, heterozygous carriers of hemophilia A with subnormal FVIII levels; patients with von Willebrand syndrome (VWD) type 1, "Vicenza type", and with VWD type 2b.

Participants will receive BT200 subcutaneously on day 0, day 4 and day 7 in the first week and then once a week for a total of five weeks - initially in a dose of 3 mg, then in week 3 individually after response in a dose of 3 to 9 mg.

Subsequently, blood samples are taken once a week for a further three weeks (wash-out phase).

Patients may be enrolled in an additional pharmacokinetics sub-study. For this purpose, approximately three blood samples are taken to estimate the half-life of substituted FVIII under the influence of BT200.

The primary objective of this study is to obtain clinical proof of mechanism for BT200 in one or more hereditary bleeding disorders.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: September 10, 2021
• Est. primary completion date: September 10, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:To be eligible for this study, patients must meet all of the following inclusion criteria:

1. Hereditary bleeding disorder:

• Congenital hemophilia A without inhibitors with a prophylactic treatment regime

• Heterozygous carriers of hemophilia A with subnormal FVIII levels

• VWD Type 1, "Vicenza" type

• VWD Type 2b

2. Male or female, age =18-70 years old at Screening

3. If female, must be post-menopausal or surgically sterilized

4. Able to comprehend and to give informed consent

5. 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: Patients meeting any of the following criteria will be excluded from the study:

1. Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the patient or compromise the quality of the data derived from his/her participation in this study

2. Medical History of spontaneous (not FVIII or FEIBA-associated) venous or arterial thromboembolic events

3. History of 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 patient 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 patient'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 -

Related Conditions & MeSH terms

• Blood Coagulation Disorders
• Hemophilia A
• Hemostatic Disorders
• Von Willebrand Diseases

Intervention

Drug:
• BT200
BT200 is a PEGylated synthetic RNA oligonucleotide

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overall safety and tolerability of BT200	Serious, drug-related adverse events (AEs)	Baseline through 4 weeks after dosing
Other	Overall safety and tolerability of BT200	Patterns of serious or non-serious, drug-related AEs and/or clinically relevant laboratory abnormalities, vital signs, or physical findings suggestive of one or more specific target organs for toxicity of BT200	Baseline through 4 weeks after dosing
Other	Overall safety and tolerability of BT200	Clinically evident bleeding assessed using the International International Society on Thrombosis and Haemostasis (ISTH) Bleeding Score	Baseline through 4 weeks after dosing
Primary	Hemophilia A	increase in FVIII activity	Baseline through 4 weeks after dosing
Primary	VWD Type 1	increase in FVIII activity	Baseline through 4 weeks after dosing
Primary	VWD Type 2b	increase in platelet count and/or FVIII activity	Baseline through 4 weeks after dosing
Secondary	Pharmacokinetic (PK) Measured concentration of BT200 (and derived PK parameters)	Measured concentration of BT200	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	PFA-100	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	Multiplate electrode platelet aggregometer (ristocetin induced)	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	VWF antigen	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	VWF:ristocetin co-factor assay	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	VWF activity	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	VWF collagen bindign assay	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	ELISA for unbound VWF-A1 domain	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	VWF propeptide	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	Fibrin D-Dimer	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	Prothrombin fragement (F1.2)	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	Rotational thrombelastometry	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	Clot strength assay	Baseline through 4 weeks after dosing
Secondary	Pharmacodynamics	Calibrated Thrombogram assay	Baseline through 4 weeks after dosing