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BT200 in Hereditary Bleeding Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04677803
Recruitment Status : Completed
First Posted : December 21, 2020
Last Update Posted : November 11, 2021
Sponsor:
Information provided by (Responsible Party):
Ulla Derhaschnig, MD, Medical University of Vienna

Brief 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.


Condition or disease Intervention/treatment Phase
Von Willebrand Diseases Hemophilia A Drug: BT200 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label, individual dose titration-to-response, basket trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2a Multiple Dose Basket Study of the Safety, Tolerability, and Pharmacologic Activity of BT200 in Patients With Hereditary Bleeding Disorders
Actual Study Start Date : December 14, 2020
Actual Primary Completion Date : September 10, 2021
Actual Study Completion Date : September 10, 2021


Arm Intervention/treatment
Experimental: Treatment

Subcutaneous (SC) injection:

BT200 dose 3 mg on Day 0, Day 4, and again on Day 7 BT200 dose titrated thereafter between 3 and 9 mg on Days 14, 21, and 28. It is anticipated that dose adjustments will be performed in 2 mg steps. The 9 mg dose will only be applied on day 28 in exceptional circumstances, if no relevant changes in pharmacodynamic and safety parameters will be observed on day 21.

Drug: BT200
BT200 is a PEGylated synthetic RNA oligonucleotide




Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 -

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04677803


Locations
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Austria
Medical University of Vienna
Vienna, Austria, A-1090
Sponsors and Collaborators
Medical University of Vienna
Investigators
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Principal Investigator: Ulla Derhaschnig, MD MU Vienna, Dept. of Clinical Pharmacology
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ulla Derhaschnig, MD, Associate Professor, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT04677803    
Other Study ID Numbers: BT200-02
First Posted: December 21, 2020    Key Record Dates
Last Update Posted: November 11, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Hemostatic Disorders
Hemophilia A
Blood Coagulation Disorders
Von Willebrand Diseases
Blood Coagulation Disorders, Inherited
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Vascular Diseases
Cardiovascular Diseases
Blood Platelet Disorders