A Study to Assess the Efficacy and Safety of Emicizumab in Participants With Type 3 Von Willebrand Disease

NCT06998524 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: WP453382024-515622-80-00
• Study Type: interventional
• Target: 75
• Locations: 14 countries
• Sites: 27

Brief Summary

This is a Phase III, multicenter, open-label clinical study designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab prophylaxis in participants aged 1 month and above, who have been diagnosed with Type 3 von Willebrand disease (VWD). Participants on prior standard of care (SOC) on-demand therapy will be assessed via a randomized comparison (Arm A - emicizumab prophylaxis and Arm B - continuation of SOC on-demand therapy), while participants on prior SOC prophylactic therapy (Arm C - emicizumab prophylaxis) will be assessed via intra-participant analysis with data obtained from the preceding non-interventional study (NIS), WP45335 (NCT06883240).

Conditions

Von Willebrand Disease, Type 3

Outcome Measures

Primary Outcomes (1)

• Annualized Bleed Rate (ABR) for Treated Bleeds in the Randomized Arms

  From Baseline to at least 24 weeks

Secondary Outcomes (25)

• ABR for All Bleeds in the Randomized Arms

  From Baseline to at least 24 weeks

• ABR for Treated Spontaneous Bleeds in the Randomized Arms

  From Baseline to at least 24 weeks

• ABR for Treated Joint Bleeds in the Randomized Arms

  From Baseline to at least 24 weeks

• Intra-Participant Comparison of the ABR for Treated Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding Non-Interventional Study (NIS) WP45335

  From Baseline to at least 24 weeks

• Intra-Participant Comparison of the ABR for All Bleeds with Prophylactic Emicizumab Versus Prophylactic SOC from the Preceeding NIS WP45335

  From Baseline to at least 24 weeks

Study Arms (4)

Arm A (Prior On-Demand SOC): Emicizumab Prophylaxis for 24 Weeks

EXPERIMENTAL

Participants who are randomized to Arm A, taking on-demand standard of care (SOC) treatment at the time of study entry (and for at least 24 weeks prior to enrollment), will receive emicizumab SC prophylaxis.

Drug: Emicizumab

Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks

ACTIVE COMPARATOR

Participants who are randomized to Arm B, taking on-demand standard of care (SOC) treatment at the time of study entry (and for at least 24 weeks prior to enrollment), will continue to receive their current SOC on-demand treatment until Week 24.

Drug: von Willebrand Factor (VWF) Concentrates; Drug: Factor VIII (FVIII) Concentrates; Drug: von Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates; Drug: Bypassing Agents

Arm C (Prior Prophylaxis SOC): Emicizumab Prophylaxis for 24 Weeks

EXPERIMENTAL

Participants who enroll in Arm C, taking SOC prophylactic treatment at the time of study entry and for at least 24 weeks of observation during the preceding NIS WP45335, will receive emicizumab SC prophylaxis.

Drug: Emicizumab

Treatment Extension Period for All Arms: Emicizumab Prophylaxis

EXPERIMENTAL

Participants in Arms A and C who have completed 24 weeks of emicizumab prophylaxis and who derive benefit from emicizumab will have the opportunity to continue to receive emicizumab prophylaxis in the extension period. Participants in Arm B who have completed 24 weeks of SOC on-demand treatment will have the opportunity to receive emicizumab prophylaxis in the extension period.

Drug: Emicizumab

Interventions

Emicizumab DRUG

Participants will receive emicizumab 3 milligrams per kilogram (mg/kg) subcutaneous (SC) injections every week (QW) for the first 4 weeks as loading doses, followed by maintenance doses of emicizumab 3 mg/kg SC once every 2 weeks (Q2W). During the extension period, participants may remain on maintenance dose of emicizumab 3 mg/kg Q2W, or change their emicizumab maintenance regimen to 1.5 mg/kg once every week (QW) or 6 mg/kg once every 4 weeks (Q4W), if they prefer and if agreed by the investigators.

Also known as: Hemlibra, RO5534262, RG6013

Arm A (Prior On-Demand SOC): Emicizumab Prophylaxis for 24 Weeks; Arm C (Prior Prophylaxis SOC): Emicizumab Prophylaxis for 24 Weeks; Treatment Extension Period for All Arms: Emicizumab Prophylaxis

von Willebrand Factor (VWF) Concentrates DRUG

Used according to local labeling or local treatment guidelines.

Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks

von Willebrand Factor (VWF) and Factor VIII (FVIII) Concentrates DRUG

Used according to local labeling or local treatment guidelines.

Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks

Factor VIII (FVIII) Concentrates DRUG

Used according to local labeling or local treatment guidelines.

Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks

Bypassing Agents DRUG

Used according to local labeling or local treatment guidelines.

Arm B (Prior On-Demand SOC): On-Demand SOC for 24 Weeks

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of Type 3 von Willebrand disease (VWD), based on medical records
• Preexisting medical record verifying the status of von Willebrand factor (VWF) inhibitor (positive or negative, including titer if available)
• Adequate hematologic, hepatic, and renal function
• For participants of childbearing potential: agreement to remain abstinent or adhere to the contraception requirements
• Age ≥1 month at the time of signing Informed Consent/Assent Form
• Documented previous use of on-demand therapy with intermittent (less than once a week) on-demand SOC therapy for VWD
• Having ≥2 treated bleeds (except menstrual bleeds) with factor concentrate within 24 weeks prior to enrollment
• Age ≥2 years at the time of signing Informed Consent/Assent Form
• Documented and confirmed previous use of SOC prophylactic therapy for VWD (1-3 times weekly, as per prescribed dose) as described in the eligibility of Study WP45335
• Have completed all study requirements as defined in the WP45335 protocol for at least 24 weeks

You may not qualify if:

• Inherited or acquired bleeding disorder other than Congenital Type 3 VWD
• History of gastrointestinal bleeding within 18 months prior to enrollment, or any previous diagnosis of angiodysplasia
• History of intracranial hemorrhage
• Previous or current treatment for thromboembolic disease or signs of thromboembolic disease
• Other conditions (e.g., certain autoimmune diseases) that may increase risk of bleeding or thrombosis
• History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
• Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (27)

UC Davis

Sacramento, California, 95817, United States

RECRUITING

University of Florida

Gainesville, Florida, 32610, United States

RECRUITING

University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

McGill University Health Center

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

IPS SURA Industriales Medellín

Medellín, Colombia

RECRUITING

Hopital Claude Huriez - CHU Lille

Lille, 59037, France

RECRUITING

Groupe Hospitalier Necker Enfants Malades

Paris, 75015, France

RECRUITING

Universitätsklinikum Bonn

Bonn, 53127, Germany

RECRUITING

Gerinnungszentrum Rhein-Ruhr;Gerinnungsambulanz

Duisburg, 47051, Germany

RECRUITING

Hämophiliezentrum Med. Klinik III/Institut für Transfusionsmedizin

Frankfurt/M., 60590, Germany

RECRUITING

Universita' Degli Studi La Sapienza-Ist.Di Ematologia

Rome, Lazio, 00161, Italy

RECRUITING

IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

RECRUITING

AOU Careggi

Florence, Tuscany, 50134, Italy

RECRUITING

Kurume University Hospital

Fukuoka, 830-0011, Japan

RECRUITING

Nagoya University Hospital

Nagoya, 466-8560, Japan

RECRUITING

Erasmus MC

Rotterdam, 3015 GD, Netherlands

RECRUITING

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

RECRUITING

Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, 2193, South Africa

RECRUITING

Hospital Universitario la Paz

Madrid, 28046, Spain

RECRUITING

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

RECRUITING

Sahlgrenska Universitetssjukhuset

Gothenburg, S-413 45, Sweden

RECRUITING

St Thomas' Hospital

London, SE1 7EH, United Kingdom

RECRUITING

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

RECRUITING

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

RECRUITING

MeSH Terms

Conditions

von Willebrand Disease, Type 3

Interventions

emicizumab; von Willebrand Factor; Factor VIII

Condition Hierarchy (Ancestors)

von Willebrand Diseases; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein 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

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

Reference Study ID Number: WP45338 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Study Design

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

Model Details: Participants on prior SOC on-demand therapy will be randomized into Arms A and B. Participants on prior SOC prophylactic therapy, who participated in the NIS WP45335 (NCT06883240) and meet the eligibility criteria for this study, will be enrolled into Arm C.

Study Record Dates

• First Submitted: May 22, 2025
• First Posted: May 31, 2025
• Study Start: June 27, 2025
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): March 30, 2029
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

ES (2); PL (1); GB (3); JP (2); BE (1); FR (2); SE (1); US (4); NL (1); DE (3); IT (3); CO (1); CA (2); ZA (1)