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

NCT04052698 | Completed Phase 3 Results FDA Drug

• 1 other identifier: WIL-31
• Study Type: interventional
• Target: 43
• Locations: 8 countries
• Sites: 14

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.

Conditions

Von Willebrand Diseases

Outcome Measures

Primary Outcomes (2)

• 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.

  12 months

• 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

  12 Months

Secondary Outcomes (7)

• Spontaneous Annualized Bleeding Rate (SABR)

  12 months

• 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.

  12 Months

• Wilate Consumption for Prophylaxis (mFAS Population)

  12 months

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

  From baseline and 12-month visit

• Incremental In Vivo Recovery (IVR) of FVIII

  Baseline and 12-month visit

Other Outcomes (6)

• Efficacy Rating for Wilate in Surgical Prophylaxis

  12 months

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

  12 months

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

  12 months

Study Arms (1)

All patients

EXPERIMENTAL

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

Drug: Wilate

Interventions

Wilate DRUG

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.

Also known as: von Willebrand factor / Factor VIII (plasma derived)

All patients

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Octapharma: lead

Study Sites (14)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

Republican Research Center for Radiation Medicine and Human Ecology

Homyel, 290, Belarus

Location

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

Sofia, Bulgaria

Location

Pediatric Clinic of Haematology and Oncology

Varna, 9010, Bulgaria

Location

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Medical Centre Hungarian Defence Forces

Budapest, 1134, Hungary

Location

Debreceni Egyetem Klinikai Központ, Regionális Haemophilia és Thrombophilia Központ

Debrecen, 4032, Hungary

Location

Hotel Dieu de France Hospital

Beirut, BP166830, Lebanon

Location

American University of Beirut Medical Center

Beirut, Lebanon

Location

Nini Hospital

Tripoli, Lebanon

Location

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

Kirov, 610027, Russia

Location

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

Moscow, 119049, Russia

Location

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

Kyiv, 01135, Ukraine

Location

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

Lviv, 79035, Ukraine

Location

Related Publications (16)

• Bodo I, Eikenboom J, Montgomery R, Patzke J, Schneppenheim R, Di Paola J; von Willebrand factor Subcommittee of the Standardization and Scientific Committee of the International Society for Thrombosis and Haemostasis. Platelet-dependent von Willebrand factor activity. Nomenclature and methodology: communication from the SSC of the ISTH. J Thromb Haemost. 2015 Jul;13(7):1345-50. doi: 10.1111/jth.12964. Epub 2015 May 9. No abstract available.

  PMID: 25858564 BACKGROUND

• Sadler JE. A revised classification of von Willebrand disease. For the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Thromb Haemost. 1994 Apr;71(4):520-5.

  PMID: 8052974 BACKGROUND

• Rodeghiero F, Castaman G, Tosetto A. How I treat von Willebrand disease. Blood. 2009 Aug 6;114(6):1158-65. doi: 10.1182/blood-2009-01-153296. Epub 2009 May 27.

  PMID: 19474451 BACKGROUND

• Castaman G, Goodeve A, Eikenboom J; European Group on von Willebrand Disease. Principles of care for the diagnosis and treatment of von Willebrand disease. Haematologica. 2013 May;98(5):667-74. doi: 10.3324/haematol.2012.077263.

  PMID: 23633542 BACKGROUND

• U S Department Of Health And Human Services. Opioid abuse in the United States and Department of Health and Human Services actions to address opioid-drug-related overdoses and deaths. J Pain Palliat Care Pharmacother. 2015 Jun;29(2):133-9. doi: 10.3109/15360288.2015.1037530.

  PMID: 26095483 BACKGROUND

• Cella D, Yount S, Rothrock N, Gershon R, Cook K, Reeve B, Ader D, Fries JF, Bruce B, Rose M; PROMIS Cooperative Group. The Patient-Reported Outcomes Measurement Information System (PROMIS): progress of an NIH Roadmap cooperative group during its first two years. Med Care. 2007 May;45(5 Suppl 1):S3-S11. doi: 10.1097/01.mlr.0000258615.42478.55.

  PMID: 17443116 BACKGROUND

• Hays RD, Spritzer KL, Schalet BD, Cella D. PROMIS(R)-29 v2.0 profile physical and mental health summary scores. Qual Life Res. 2018 Jul;27(7):1885-1891. doi: 10.1007/s11136-018-1842-3. Epub 2018 Mar 22.

  PMID: 29569016 BACKGROUND

• Maruish M. User's manual for the SF-36v2 Health Survey (3rd edition). Optum Incorporated; 2011.

  BACKGROUND

• Saris-Baglama, R,DeRosa, M, Raczek, A, Bjorner, J,Turner-Bowker, D, Ware, J. The SF-10™ Health Survey for Children: A User's Guide. QualityMetric Incorporated; 2007.

  BACKGROUND

• Feldman BM, Funk SM, Bergstrom BM, Zourikian N, Hilliard P, van der Net J, Engelbert R, Petrini P, van den Berg HM, Manco-Johnson MJ, Rivard GE, Abad A, Blanchette VS. Validation of a new pediatric joint scoring system from the International Hemophilia Prophylaxis Study Group: validity of the hemophilia joint health score. Arthritis Care Res (Hoboken). 2011 Feb;63(2):223-30. doi: 10.1002/acr.20353.

  PMID: 20862683 BACKGROUND

• van Galen KPM, Timmer MA, de Kleijn P, Fischer K, Foppen W, Schutgens REG, Eikenboom J, Meijer K, Cnossen MH, Fijnvandraat K, van der Bom JG, Laros-van Gorkom BAP, Leebeek FWG, Mauser-Bunschoten EP, Win Study Group OBOT. Joint assessment in von Willebrand disease. Validation of the Haemophilia Joint Health score and Haemophilia Activities List. Thromb Haemost. 2017 Aug 1;117(8):1465-1470. doi: 10.1160/TH16-12-0967. Epub 2017 May 11.

  PMID: 28492695 BACKGROUND

• Janssen CA, Scholten PC, Heintz AP. A simple visual assessment technique to discriminate between menorrhagia and normal menstrual blood loss. Obstet Gynecol. 1995 Jun;85(6):977-82. doi: 10.1016/0029-7844(95)00062-V.

  PMID: 7770270 BACKGROUND

• Higham JM, O'Brien PM, Shaw RW. Assessment of menstrual blood loss using a pictorial chart. Br J Obstet Gynaecol. 1990 Aug;97(8):734-9. doi: 10.1111/j.1471-0528.1990.tb16249.x.

  PMID: 2400752 BACKGROUND

• Djambas Khayat C, Dubey L, Inati A, Lissitchkov T, Novik D, Peteva E, Sidonio RF Jr, Taher AT, Vilchevska KV, Vdovin V, Boban A. Efficacy and Safety of Prophylaxis With a Plasma-Derived von Willebrand Factor/Factor VIII Concentrate (Wilate) in Patients With Type 3 von Willebrand Disease-A WIL-31 Study Sub-Analysis. Eur J Haematol. 2026 Jan 30. doi: 10.1111/ejh.70117. Online ahead of print.

  PMID: 41614378 DERIVED

• Sidonio RF Jr, Boban A, Lissitchkov T, Nemes L, Vdovin V, Khayat CD. Individualizing dosing frequency may improve the efficacy of prophylaxis in patients with von Willebrand disease-a WIL-31 subanalysis. Res Pract Thromb Haemost. 2025 Oct 10;9(7):103221. doi: 10.1016/j.rpth.2025.103221. eCollection 2025 Oct.

  PMID: 41278463 DERIVED

• Sidonio RF Jr, Boban A, Dubey L, Inati A, Kiss C, Boda Z, Lissitchkov T, Nemes L, Novik D, Peteva E, Taher AT, Timofeeva MA, Vilchevska KV, Vdovin V, Werner S, Knaub S, Djambas Khayat C. von Willebrand factor/factor VIII concentrate (Wilate) prophylaxis in children and adults with von Willebrand disease. Blood Adv. 2024 Mar 26;8(6):1405-1414. doi: 10.1182/bloodadvances.2023011742.

  PMID: 38237075 DERIVED

Related Links

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

MeSH Terms

Conditions

von Willebrand Diseases

Interventions

von Willebrand Factor; Factor VIII

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

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors; Protein Precursors

Results Point of Contact

• Title: Dr. Sigurd Knaub, Senior VP CR&D Haematology
• Organization: Octapharma

Sigurd.Knaub@octapharma.com

01554512141

Study Officials

• Cristina Solomon

  Octapharma

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2019
• First Posted: August 12, 2019
• Study Start: June 18, 2020
• Primary Completion: April 23, 2022
• Study Completion: April 23, 2022
• Last Updated: October 25, 2023
• Results First Posted: October 25, 2023

Record last verified: 2023-09

Locations

RU (2); US (1); UA (2); CR (1); BU (2); HU (2); BE (1); LE (3)