A study to determine the effectiveness and Safety of rVWF used to prevent bleeding episodes in patients with severe von Willebrand disease

Phase 1

• Conditions: Hereditary severe von Willebrand Disease; MedDRA version: 20.0Level: PTClassification code 10047715Term: Von Willebrand's diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 20.0Level: LLTClassification code 10055168Term: Von Willebrand's factor deficiencySystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2016-001478-14-DE
• Lead Sponsor: Baxalta Innovations GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-01-03
• Last Update Posted: 7 December 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

Subjects who meet ALL of the following criteria are eligible for this study:
1. Subject has a documented diagnosis of severe VWD (baseline VWF:RCo <20 IU/dL) with a history
of requiring substitution therapy with von Willebrand factor concentrate to control bleeding:
a. Type 1 (VWF:RCo <20 IU/dL) or,
b. Type 2A (as verified by multimer pattern), Type 2B (as diagnosed by genotype), Type 2M or,
c. Type 3 (VWF:Ag =3 IU/dL).

2. Diagnosis is confirmed by genetic testing and multimer analysis, documented in patient history or at
screening.

3. For on-demand patient group, subject currently receiving on-demand
treatment for whom prophylactic treatment is recommended by the
investigator.

4. For pdVWF switch patient group, subject has been receiving
prophylactic treatment of pdVWF products for no less than 12 months
prior to screening.

5. For on-demand patient group, subject has =3 documented
spontaneous bleeds (not including menorrhagia) requiring VWF
treatment during the past 12 months.

6. Availability of records to reliably evaluate type, frequency and
treatment of bleeding episodes during at least 12 months preceding
enrollment.
Up to 24 months of retrospective data should be collected if available.
Availability of dosing and factor consumption during 12 months (up to
24 months) of treatment prior to enrollment is required for pdVWF
switch subjects and is desired (but not a requirement) for on-demand
subjects.

7. Subject is =18 years old at the time of screening and has a body mass
index =15 but <40 kg/m2.

8. If female of childbearing potential, subject presents with a negative blood/urine pregnancy test at
screening and agrees to employ adequate birth control measures for the duration of the study.

9. Subject is willing and able to comply with the requirements of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 17
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

Subjects who meet ANY of the following criteria are not eligible for this
study:

1. The subject has been diagnosed with Type 2N VWD, pseudo VWD, or
another hereditary or acquired coagulation disorder other than VWD
(e.g., qualitative and quantitative platelet disorders or elevated
prothrombin time (PT)/international normalized ratio [INR] 1.4).

2. The subject is currently receiving prophylactic treatment with more
than 5 infusions per week.

3. The subject is currently receiving prophylactic treatment with a
weekly dose exceeding 240 IU/kg.

4. The subject has a history or presence of a VWF inhibitor at screening.

5. The subject has a history or presence of a FVIII inhibitor with a titer =
0.4 Bethesda units (BU) (by Nijmegen modified Bethesda assay) or =0.6
BU (by Bethesda assay).(by Nijmegen modified Bethesda assay) or =0.6 BU (by Bethesda assay).

6. The subject has a known hypersensitivity to any of the components of the study drugs, such as to mouse or hamster proteins.

7. The subject has a medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis, mild asthma, food allergies or animal allergies.

8. The subject has a medical history of a thromboembolic event.

9. The subject is human immunodeficiency virus (HIV) positive with an
absolute Helper T cell (CD4) count 200/mm3.

10. The subject has been diagnosed with significant liver disease per
investigator's medical assessment of the subject's current condition or
medical history or as evidenced by any of the following:
serum alanine aminotransferase (ALT) greater than 5 times the upper
limit of normal; hypoalbuminemia; portal vein hypertension (e.g.,
presence of otherwise unexplained splenomegaly, history of esophageal
varices).

11. The subject has been diagnosed with renal disease, with a serum creatinine (CR) level =2.5 mg/dL.

12. The subject has a platelet count <100,000/mL at screening.

13. The subject has been treated with an immunomodulatory drug, excluding topical treatment (e.g.,ointments, nasal sprays), within 30 days prior to signing the informed consent.

14. The subject is pregnant or lactating at the time of enrollment.

15. Patient has cervical or uterine conditions causing menorrhagia or metrorrhagia (including infection,dysplasia).

16. The subject has participated in another clinical study involving another investigational product (IP)or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.

17. The subject has a progressive fatal disease and/or life expectancy of less than 15 months.

18. The subject is scheduled for a surgical intervention.

19. The subject is identified by the investigator as being unable or unwilling to cooperate with study procedures.

20. The subject has a mental condition rendering him/her unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.

21. The subject is in prison or compulsory detention by regulatory and/or juridical order

22. The subject is member of the study team or in a dependent relationship with one of the study team
members which includes close relatives (i.e., children, partner/spouse, siblings and parents) as well
as employees.

Delay criteria
1. If the subject presents with an acute bleeding episodes or acute il

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to prospectively evaluate the<br>annualized bleeding rate (ABR) for spontaneous bleeding episodes while<br>on prophylactic treatment with rVWF (vonicog alfa) and to compare it to<br>the subject's historical ABR for spontaneous bleeding episodes.;Secondary Objective: Secondary Objectives are to assess<br>Additional efficacy of prophylactic treatment with rVWF (vonicog alfa)<br>Safety of rVWF (vonicog alfa), including immunogenicity,<br>thrombogenicity and hypersensitivity<br>Pharmacokinetics (PK) of rVWF (vonicog alfa) and Pharmacodynamics<br>(PD) of requiredrVWF (vonicog alfa) as measured in FVIII activity;Primary end point(s): Annualized bleeding rate (ABR) for spontaneous (not related to trauma)<br>bleeding episodes during prophylactic treatment with rVWF vonicog<br>alfa).;Timepoint(s) of evaluation of this end point: On completion of 12 month prophylactic treatment.