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Clinical Study to Investigate the Efficacy and Safety of Wilate During Prophylaxis in Previously Treated Patients With VWD

Primary Purpose

Von Willebrand Diseases

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Wilate

About this trial

This is an interventional treatment trial for Von Willebrand Diseases

Eligibility Criteria

6 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients who meet all of the following criteria are eligible for the study:

Aged ≥6 years at the time of screening
VWD type 1 (baseline von Willebrand factor activity [VWF:Ristocetin Co-factor (RCo)] <30 IU/dL, 2A, 2B, 2M, or 3 according to medical history requiring substitution therapy with a VWF-containing product to control bleeding
Currently receiving on-demand treatment with a VWF-containing product with at least 1, and an average of ≥2, documented spontaneous BEs per month in the last 6 months, with at least 2 of these BEs requiring treatment with a VWF-containing product
Availability of records to reliably evaluate type, frequency, and treatment of BEs for at least 6 months of on-demand treatment before screening
Female patients of child-bearing potential must have a negative urine pregnancy test at screening and agree to use adequate birth control measures; in case hormonal contra-ception is used, the medication class should remain unchanged for the duration of the study
All patients to provide voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted

Exclusion Criteria:

Patients who meet any of the following criteria are not eligible for the study:

Having received on-demand or prophylactic treatment with a VWF-containing product but having no records available to reliably evaluate the type, frequency, and treatment of BEs over a period of at least 6 months of on-demand treatment
History, or current suspicion, of VWF or FVIII inhibitors
Medical history of a thromboembolic event within 1 year before enrolment
Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate trans-aminase [ASAT] levels >5 times of upper limit of normal, creatinine >120 µmol/L)
Platelet count <100,000/µL at screening (except for VWD type 2B)
Body weight <20 kg at screening
Patients receiving, or scheduled to receive, immunosuppressant drugs (other than an-tiretroviral chemotherapy), such as prednisone (equivalent to >10 mg/day), or similar drugs
Pregnant or breast-feeding at the time of enrolment
Cervical or uterine conditions causing abnormal uterine bleeding (including infection, dysplasia)
Treatment with any IMP in another interventional clinical study currently or within 4 weeks before enrolment
Other coagulation disorders or bleeding disorders due to anatomical reasons
Known hypersensitivity to any of the components of the study drug

Sites / Locations

Children's Healthcare of Atlanta
Republican Research Center for Radiation Medicine and Human Ecology
"Specialized Hospital for Active Treatment of Haematological Diseases" EAD, Sofia
Pediatric Clinic of Haematology and Oncology
University Hospital Centre Zagreb
Medical Centre Hungarian Defence Forces
Debreceni Egyetem Klinikai Központ, Regionális Haemophilia és Thrombophilia Központ
Hotel Dieu de France Hospital
American University of Beirut Medical Center
Nini Hospital
Federal State Budgetary Scientific Institution Kirov Scientific-Research Institute of Hematology and Blood Transfusion of Federal
Morosovskaya Children Clinical Hospital, Moscow Health Department, Department of General Hematology with the Pathology of Hemostasis
State Institution "National Children's Specialized Hospital "OKHMATDYT" of the Ministry of Health of Ukraine," Center of Hemostasis Pathology
Communal Nonprofit Enterprise "Western Ukrainian Specialized Children's Medical Center"of Lviv Regional Council

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

All patients

Arm Description

Patients with type 3, type 2 (except 2N), or severe type 1 VWD aged ≥6 years at screening receiving Wilate for prophylactic treatment.

Outcomes

Primary Outcome Measures

Total Annualized Bleeding Rate (TABR)

The TABR was calculated as the total number of spontaneous bleeds, traumatic bleeds, and other bleeds (except menstrual bleeds) occurring in the time period between first dose of the investigational medicinal product (IMP) and the Study Completion Visit, divided by the duration (in years) between first dose of IMP and the Study Completion Visit.

Comparison of Total Annualized Bleeding Rates (TABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29

Estimated TABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread

Secondary Outcome Measures

Spontaneous Annualized Bleeding Rate (SABR)

Spontaneous annualized bleeding rate (SABR) calculated in analogy with TABR

Comparison of Spontaneous Annualized Bleeding Rates (SABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29.

Estimated SABR number calculated using a negative binomial counting regression model. Comparison between this number calculated for studies WIL-29 (NCT04053699) and WIL-31. For the comparison of results from WIL-31 to WIL-29 an estimated total annualized bleeding rate was calculated for each cohort, and compared with a negative binomial counting model. As these were estimated rates, there is only one value for each cohort with no measure of spread

Wilate Consumption for Prophylaxis (mFAS Population)

Data on the consumption of Wilate (VWF/FVIII IU/kg per month and per week per patient) for prophylactic treatment

Incremental In Vivo Recovery (IVR) of Von Willebrand Factor Activity (VWF:RCo)

Incremental VWF:RCo IVR of Wilate over time (at baseline and at 1, 2, 3, 6, 9, and 12 months of treatment)

Incremental In Vivo Recovery (IVR) of FVIII

FVIII:C of Wilate in pediatric patients (at baseline PK visit) measured by chromogenic assay

Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)

Treatment efficacy will be assessed at the end of a BE by the patient using predefined criteria of 'Excellent', 'Good', 'Moderate' or 'None'. All effectiveness ratings assessed as either "excellent" or "good" will be considered "successfully treated".

Wilate Exposure for Prophylaxis (mFAS Population)

Data on the exposure days of Wilate prophylactic treatment

Full Information

NCT ID

NCT04052698

First Posted

August 9, 2019

Last Updated

September 29, 2023

Sponsor

Octapharma

1. Study Identification

Unique Protocol Identification Number

NCT04052698

Brief Title

Clinical Study to Investigate the Efficacy and Safety of Wilate During Prophylaxis in Previously Treated Patients With VWD

Official Title

Clinical Study to Investigate the Efficacy and Safety of Wilate During Prophylaxis in Previously Treated Patients With Von Willebrand Disease (VWD)

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

June 18, 2020 (Actual)

Primary Completion Date

April 23, 2022 (Actual)

Study Completion Date

April 23, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Octapharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This is a prospective, non-controlled, international, multi-center phase 3 study investigating the efficacy and safety of Wilate in previously treated adult patients with VWD, to obtain additional data on the safety and efficacy of Wilate in previously treated patients with VWD undergoing regular prophylaxis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Von Willebrand Diseases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

43 (Actual)

8. Arms, Groups, and Interventions

Arm Title

All patients

Arm Type

Experimental

Arm Description

Patients with type 3, type 2 (except 2N), or severe type 1 VWD aged ≥6 years at screening receiving Wilate for prophylactic treatment.

Intervention Type

Drug

Intervention Name(s)

Wilate

Other Intervention Name(s)

von Willebrand factor / Factor VIII (plasma derived)

Intervention Description

Produced from the plasma of human donors, Wilate is presented as a powder or solvent for intravenous injection containing normally 500 IU or 1000 IU human VWF and human FVIII per vial. The ratio between VWF ristocetin co-factor activity (VWF:RCo) and FVIII:C is 1:1. The product contains approximately 100 IU/ml human VWF when reconstituted with 5ml/10mL water for injection with 0.1% polysorbate 80. The specific activity of Wilate is ≥67 IU VWF:RCo/mg protein. The injection or infusion rate should not exceed 2-3mL per minute.

Primary Outcome Measure Information:

Title

Total Annualized Bleeding Rate (TABR)

Description

Time Frame

12 months

Title

Comparison of Total Annualized Bleeding Rates (TABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29

Description

Time Frame

12 Months

Secondary Outcome Measure Information:

Title

Spontaneous Annualized Bleeding Rate (SABR)

Description

Spontaneous annualized bleeding rate (SABR) calculated in analogy with TABR

Time Frame

12 months

Title

Comparison of Spontaneous Annualized Bleeding Rates (SABR) During Prophylaxis Treatment in Study WIL-31 to On-demand Treatment in the Same Patient Population in the Preceding Study WIL-29.

Description

Time Frame

12 Months

Title

Wilate Consumption for Prophylaxis (mFAS Population)

Description

Data on the consumption of Wilate (VWF/FVIII IU/kg per month and per week per patient) for prophylactic treatment

Time Frame

12 months

Title

Incremental In Vivo Recovery (IVR) of Von Willebrand Factor Activity (VWF:RCo)

Description

Incremental VWF:RCo IVR of Wilate over time (at baseline and at 1, 2, 3, 6, 9, and 12 months of treatment)

Time Frame

From baseline and 12-month visit

Title

Incremental In Vivo Recovery (IVR) of FVIII

Description

FVIII:C of Wilate in pediatric patients (at baseline PK visit) measured by chromogenic assay

Time Frame

Baseline and 12-month visit

Title

Efficacy of Wilate in the Treatment of Breakthrough Bleeding Events (BEs)

Description

Time Frame

12 months

Title

Wilate Exposure for Prophylaxis (mFAS Population)

Description

Data on the exposure days of Wilate prophylactic treatment

Time Frame

12 months

Other Pre-specified Outcome Measures:

Title

Efficacy Rating for Wilate in Surgical Prophylaxis

Description

Efficacy will be assessed by the surgeon at the end of surgery and by the hematologist at the end of the postoperative period using predefined criteria of 'Excellent', 'Good', 'Moderate' or 'None'. In addition, an overall assessment using the 'Excellent', 'Good', 'Moderate' or 'None' scale taking both the intra- and postoperative assessments into account will be made at the end of the postoperative period by the investigator based on an algorithm.

Time Frame

12 months

Title

Quality of Life (QoL) Assessed Using the Patient-Reported Outcomes Measurement Information System (PROMIS-29)

Description

QoL assessment based on the results from the PROMIS-29 (Patient-Reported Outcomes Measurement Information System) survey, which monitors and evaluates the physical, mental, and social health in all patients. The survey covers seven domains from the most relevant areas of self-reported health (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance and ability to participate in social roles and activities) for the majority of people with chronic illness, each domain using a scale of a minimum score of 0 and a maximum score of 10. Derived T-score values are presented with higher scores equalling higher levels of the outcome being measured (e.g. more fatigue, more physical function). T-scores were calculated using the scoring service from the HealthMeasures Assessment Center. For this T-score metric 50 is the mean of a relevant reference population and 10 is the standard deviation (SD) of that population.

Time Frame

12 months

Title

Quality of Life (QoL) Assessed Using a 36-Item Short Form Health Survey, Version 2 (SF-36v2)

Description

QoL assessment based on the results from the SF-36v2 (Short Form Health Survey) questionnaire to measure functional health and well-being in patients ≥16 years. SF-36v2 ranks 8 different domains using a scale standardized with a scoring algorithm to obtain a score ranging from 0 to 100. The eight health domains include physical functioning (PF), role physical (RP), bodily pain (BP), general health problems (GH), vitality (VT), social functioning (SF), role emotional (RE) and general mental health (MH). Norm-based scoring is used for the SF-36, setting the general population mean to 50 and the SD to 10 for all scales. Scores typically range from 20 to 60, with higher scores indicating better health.

Time Frame

12 months

Title

Quality of Life (QoL) Assessed Using a 10-Item Short Form Health Survey (SF-10)

Description

QoL assessment based on the results from a SF-10 parent-completed questionnaire for patients ≥6 and <16 years of age, in order to score physical and psychosocial health. Norm-based scoring is used for the SF-36, setting the general population mean to 50 and the SD to 10 for all scales. Scores typically range from 20 to 60, with higher scores indicating better health.

Time Frame

12 months

Title

Joint Health Status Assessed Using Hemophilia Joint Health Score (HJHS)

Description

Joint health status will be assessed using the Hemophilia Joint Health Score (HJHS), which has been specifically validated for the assessment of the clinical outcome in VWD. HJHS evaluates six index joints to produce a score between 0-124. The maximum score for an individual index joint is 20. Higher scores indicate worse joint health.

Time Frame

Baseline and 12 months

Title

Menstrual Bleeding Assessed Using Pictorial Blood Loss Assessment Chart (PBAC) Score

Description

Bleeding information from each menstrual period while in this study will be collected using the Pictorial Blood Loss Assessment Chart (PBAC). The PBAC will be provided to all female patients of child-bearing potential. The data documented in the PBAC and the investigator-calculated final score will be recorded in the electronic case report form (eCRF). The PBAC score is from 0 onwards, with no theoretical maximum. A score of >100 defines abnormal coagulation and heavy menstrual bleeding (>80ml of blood loss per menstrual cycle).

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients who meet all of the following criteria are eligible for the study: Aged ≥6 years at the time of screening VWD type 1 (baseline von Willebrand factor activity [VWF:Ristocetin Co-factor (RCo)] <30 IU/dL, 2A, 2B, 2M, or 3 according to medical history requiring substitution therapy with a VWF-containing product to control bleeding Currently receiving on-demand treatment with a VWF-containing product with at least 1, and an average of ≥2, documented spontaneous BEs per month in the last 6 months, with at least 2 of these BEs requiring treatment with a VWF-containing product Availability of records to reliably evaluate type, frequency, and treatment of BEs for at least 6 months of on-demand treatment before screening Female patients of child-bearing potential must have a negative urine pregnancy test at screening and agree to use adequate birth control measures; in case hormonal contra-ception is used, the medication class should remain unchanged for the duration of the study All patients to provide voluntarily given, fully informed written and signed consent obtained before any study-related procedures are conducted Exclusion Criteria: Patients who meet any of the following criteria are not eligible for the study: Having received on-demand or prophylactic treatment with a VWF-containing product but having no records available to reliably evaluate the type, frequency, and treatment of BEs over a period of at least 6 months of on-demand treatment History, or current suspicion, of VWF or FVIII inhibitors Medical history of a thromboembolic event within 1 year before enrolment Severe liver or kidney diseases (alanine aminotransferase [ALAT] and aspartate trans-aminase [ASAT] levels >5 times of upper limit of normal, creatinine >120 µmol/L) Platelet count <100,000/µL at screening (except for VWD type 2B) Body weight <20 kg at screening Patients receiving, or scheduled to receive, immunosuppressant drugs (other than an-tiretroviral chemotherapy), such as prednisone (equivalent to >10 mg/day), or similar drugs Pregnant or breast-feeding at the time of enrolment Cervical or uterine conditions causing abnormal uterine bleeding (including infection, dysplasia) Treatment with any IMP in another interventional clinical study currently or within 4 weeks before enrolment Other coagulation disorders or bleeding disorders due to anatomical reasons Known hypersensitivity to any of the components of the study drug

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Cristina Solomon

Organizational Affiliation

Octapharma

Official's Role

Study Director

Facility Information:

Facility Name

Children's Healthcare of Atlanta

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30329

Country

United States

Facility Name

Republican Research Center for Radiation Medicine and Human Ecology

City

Gomel

ZIP/Postal Code

290

Country

Belarus

Facility Name

"Specialized Hospital for Active Treatment of Haematological Diseases" EAD, Sofia

City

Sofia

Country

Bulgaria

Facility Name

Pediatric Clinic of Haematology and Oncology

City

Varna

ZIP/Postal Code

9010

Country

Bulgaria

Facility Name

University Hospital Centre Zagreb

City

Zagreb

ZIP/Postal Code

10000

Country

Croatia

Facility Name

Medical Centre Hungarian Defence Forces

City

Budapest

ZIP/Postal Code

1134

Country

Hungary

Facility Name

Debreceni Egyetem Klinikai Központ, Regionális Haemophilia és Thrombophilia Központ

City

Debrecen

ZIP/Postal Code

4032

Country

Hungary

Facility Name

Hotel Dieu de France Hospital

City

Beirut

ZIP/Postal Code

BP166830

Country

Lebanon

Facility Name

American University of Beirut Medical Center

City

Beirut

Country

Lebanon

Facility Name

Nini Hospital

City

Tripoli

Country

Lebanon

Facility Name

Federal State Budgetary Scientific Institution Kirov Scientific-Research Institute of Hematology and Blood Transfusion of Federal

City

Kirov

ZIP/Postal Code

610027

Country

Russian Federation

Facility Name

Morosovskaya Children Clinical Hospital, Moscow Health Department, Department of General Hematology with the Pathology of Hemostasis

City

Moscow

ZIP/Postal Code

119049

Country

Russian Federation

Facility Name

State Institution "National Children's Specialized Hospital "OKHMATDYT" of the Ministry of Health of Ukraine," Center of Hemostasis Pathology

City

Kyiv

ZIP/Postal Code

01135

Country

Ukraine

Facility Name

Communal Nonprofit Enterprise "Western Ukrainian Specialized Children's Medical Center"of Lviv Regional Council

City

Lviv

ZIP/Postal Code

79035

Country

Ukraine

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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25858564

Citation

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Links:

URL

http://www.healthmeasures.net/explore-measurement-systems/promis

Description

U.S Department of Health and Human Services, Health Measures

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Clinical Study to Investigate the Efficacy and Safety of Wilate During Prophylaxis in Previously Treated Patients With VWD

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