BT200 in Hereditary Bleeding Disorders

NCT04677803 | Completed Phase 2

• 1 other identifier: BT200-02
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

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.

Conditions

Von Willebrand Diseases; Hemophilia A

Outcome Measures

Primary Outcomes (3)

• Hemophilia A

  increase in FVIII activity

  Baseline through 4 weeks after dosing

• VWD Type 1

  increase in FVIII activity

  Baseline through 4 weeks after dosing

• VWD Type 2b

  increase in platelet count and/or FVIII activity

  Baseline through 4 weeks after dosing

Secondary Outcomes (14)

• Pharmacokinetic (PK) Measured concentration of BT200 (and derived PK parameters)

  Baseline through 4 weeks after dosing

• Pharmacodynamics

  Baseline through 4 weeks after dosing

• Pharmacodynamics

  Baseline through 4 weeks after dosing

• Pharmacodynamics

  Baseline through 4 weeks after dosing

• Pharmacodynamics

  Baseline through 4 weeks after dosing

Other Outcomes (3)

• Overall safety and tolerability of BT200

  Baseline through 4 weeks after dosing

• Overall safety and tolerability of BT200

  Baseline through 4 weeks after dosing

• Overall safety and tolerability of BT200

  Baseline through 4 weeks after dosing

Study Arms (1)

Treatment

EXPERIMENTAL

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

Interventions

BT200 DRUG

BT200 is a PEGylated synthetic RNA oligonucleotide

Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 -

You may not qualify if:

• 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 -

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, A-1090, Austria

Location

Related Publications (2)

• Ay C, Kovacevic KD, Kraemmer D, Schoergenhofer C, Gelbenegger G, Firbas C, Quehenberger P, Jilma-Stohlawetz P, Gilbert JC, Zhu S, Beliveau M, Koenig F, Iorio A, Jilma B, Derhaschnig U, Pabinger I. The von Willebrand factor-binding aptamer rondaptivon pegol as a treatment for severe and nonsevere hemophilia A. Blood. 2023 Mar 9;141(10):1147-1158. doi: 10.1182/blood.2022016571.

  PMID: 36108308 DERIVED

• Ay C, Pabinger I, Kovacevic KD, Gelbenegger G, Schorgenhofer C, Quehenberger P, Jilma-Stohlawetz P, Sunder-Plassman R, Gilbert JC, Zhu S, Jilma B, Derhaschnig U. The VWF binding aptamer rondoraptivon pegol increases platelet counts and VWF/FVIII in type 2B von Willebrand disease. Blood Adv. 2022 Sep 27;6(18):5467-5476. doi: 10.1182/bloodadvances.2022007805.

  PMID: 35772170 DERIVED

MeSH Terms

Conditions

von Willebrand Diseases; Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Blood Platelet Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ulla Derhaschnig, MD

  MU Vienna, Dept. of Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Open-label, individual dose titration-to-response, basket trial

Study Record Dates

• First Submitted: December 3, 2020
• First Posted: December 21, 2020
• Study Start: December 14, 2020
• Primary Completion: September 10, 2021
• Study Completion: September 10, 2021
• Last Updated: November 11, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)