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Completed

NCT Number: NCT04677803

BT200 in Hereditary Bleeding Disorders

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.

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Key information

Conditions

Von Willebrand Diseases Blood Coagulation Disorders Blood Coagulation Disorders, Inherited Blood Platelet Disorders Coagulation Protein Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemophilia A Hemorrhagic Disorders

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Medical University of Vienna

Vienna, A-1090, Austria

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

  • 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
  • Male or female, age ≥18-70 years old at Screening
  • If female, must be post-menopausal or surgically sterilized
  • 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 -

Exclusion criteria

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

  • 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
  • Medical History of spontaneous (not FVIII or FEIBA-associated) venous or arterial thromboembolic events
  • History of 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 patient 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 patient'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 -

Treatment and study plan

BT200

Drug

BT200 is a PEGylated synthetic RNA oligonucleotide

Primary outcomes

  1. Hemophilia A

    Time frame: Baseline through 4 weeks after dosing

    increase in FVIII activity

  2. VWD Type 1

    Time frame: Baseline through 4 weeks after dosing

    increase in FVIII activity

  3. VWD Type 2b

    Time frame: Baseline through 4 weeks after dosing

    increase in platelet count and/or FVIII activity

Secondary outcomes

  1. Pharmacokinetic (PK) Measured concentration of BT200 (and derived PK parameters)

    Time frame: Baseline through 4 weeks after dosing

    Measured concentration of BT200

  2. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    PFA-100

  3. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    Multiplate electrode platelet aggregometer (ristocetin induced)

  4. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    VWF antigen

  5. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    VWF:ristocetin co-factor assay

  6. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    VWF activity

  7. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    VWF collagen bindign assay

  8. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    ELISA for unbound VWF-A1 domain

  9. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    VWF propeptide

  10. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    Fibrin D-Dimer

  11. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    Prothrombin fragement (F1.2)

  12. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    Rotational thrombelastometry

  13. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    Clot strength assay

  14. Pharmacodynamics

    Time frame: Baseline through 4 weeks after dosing

    Calibrated Thrombogram assay

Other outcomes

  1. Overall safety and tolerability of BT200

    Time frame: Baseline through 4 weeks after dosing

    Serious, drug-related adverse events (AEs)

  2. Overall safety and tolerability of BT200

    Time frame: Baseline through 4 weeks after dosing

    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

  3. Overall safety and tolerability of BT200

    Time frame: Baseline through 4 weeks after dosing

    Clinically evident bleeding assessed using the International International Society on Thrombosis and Haemostasis (ISTH) Bleeding Score

Sponsors and collaborators

Lead sponsor

Medical University of Vienna

Other

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Dec 21, 2020
Registry last updated
Nov 11, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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