A Pilot Crossover Trial of Prophylactic Wilate Compared to Placebo for Heavy Menstrual Bleeding in Patients with VWD

NCT06205095 | Recruiting Phase 3

• 1 other identifier: 2.5
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The EMPOWER trial is a pilot multi-center, placebo-controlled (normal saline), double-blind (patient and outcome assessor), crossover, 2-year randomized trial in female outpatients with von Willebrand disease (VWD) and heavy menstrual bleeding to determine trial feasibility and viability, and to explore assay sensitivity of the proposed efficacy clinical outcomes for a definitive randomized controlled trial

Conditions

Von Willebrand Diseases

Outcome Measures

Primary Outcomes (5)

• Blinding Index (BI) score at the end of cycle 4 of treatment period 1 and 2

  Blinding Index (BI) score at the end of cycle 4 of treatment period 1 and 2

  2 years

• Proportion of participant drop-out at the end of treatment period 1 and 2

  Proportion of participant drop-out at the end of treatment period 1 and 2

  2 years

• Proportion of participants with completed for the candidate primary clinical efficacy outcomes at the end of treatment period 1 and 2

  Proportion of patients with completed for the candidate primary clinical efficacy outcomes at the end of treatment period 1 and 2

  2 years

• Number of participants enrolled in 2 years (i.e. ability to enroll at least 10 participants in 2 years)

  Ability to enroll at least 10 participants in 2 years

  2 years

• Proportion of participants with carryover effect for the candidate primary clinical efficacy outcomes from period 1 to period 2

  Proportion of participants with carryover effect for the candidate primary clinical efficacy outcomes from period 1 to period 2

  2 years

Secondary Outcomes (22)

• Mean of the 3 highest daily Modified PBAC (mPBAC) scores within each individual participant cycle averaged across 4 individual participant cycles at the end of each treatment period

  At the end of 8 menstrual cycles (approximately 10 days)

• The proportion of patients who use of rescue therapy at the end of each treatment period

  At the end of 8 menstrual cycles (approximately 10 days)

• Mean of the mPBAC score within each individual participant cycle averaged across 4 individual participant cycles

  At the end of 8 menstrual cycles (approximately 10 days)

• Median of the mPBAC score within each individual participant cycle used to derive the median across 4 individual participant cycles

  At the end of 8 menstrual cycles (approximately 10 days)

• Number of days of oral tranexamic acid use

  At the end of 8 menstrual cycles (approximately 10 days)

Study Arms (2)

pdVWF:FVIII concentrate (Wilate®) Treatment and Standard Care

EXPERIMENTAL

Wilate® at a dose of 30-60 IU VWF:RCo/kg for the two anticipated heaviest days of bleeding every 24-48 hours within the first 4 days of menstruation will be provided. Additional two optional doses 24-48 hours from the last can be provided. A minimum of 2 doses must be provided.

Drug: Lyophilized concentrate of human coagulation von Willebrand Factor and factor VIII

Placebo and Standard Care

PLACEBO COMPARATOR

Patients randomized to the placebo arm will receive intravenous placebo (normal saline) at the same approximate volume and frequency as the study drug.

Other: Placebo

Interventions

Lyophilized concentrate of human coagulation von Willebrand Factor and factor VIII DRUG

Wilate® is a plasma-derived, highly purified concentrate administered through intravenous injection. Wilate® contains an average VWF ristocetin cofactor activity to FVIII activity at ratio of 1:1.

Also known as: Wilate

pdVWF:FVIII concentrate (Wilate®) Treatment and Standard Care

Placebo OTHER

Patients randomized to the placebo arm will receive intravenous normal saline at the same approximate volume and frequency of Wilate ®.

Placebo and Standard Care

Eligibility Criteria

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

You may qualify if:

• Patient capable of providing informed consent;
• Female patients with HMB over the age of 18 years, for whom prophylactic treatment with Wilate® is deemed clinically appropriate according to the medical discretion (based on their expert opinion given consideration of the patient's bleeding history and responsiveness to treatment) of the treating hemostasis-focused physician practicing at a Hemophilia Treatment Center;
• Modified PBAC score \> 100 at screening;
• Patients with a diagnosis of inherited von Willebrand disease (any type);
• Stable treatment for HMB and iron deficiency anemia for 3 cycles before entering the study and anticipated to remain unchanged for the duration of the study;
• Patients willing to have an infusion administered by a nurse over the course of the study period;
• Patients who agree to use only the feminine hygiene products supplied by the sponsor.

You may not qualify if:

• Diagnosed with any other known bleeding disorder;
• Pregnancy or plans to become pregnant within the duration of the study;
• Breastfeeding or plans to breastfeed within the duration of the study;
• Known hypersensitivity reactions to human plasma-derived products or any ingredient in the formulation;
• Known antibodies to VWF or FVIII;
• Severe liver disease;
• Anticipated initiation of the following: oral, transdermal, injectable, and vaginal ring hormonal contraceptives; GnRH analogues; or a hormonal intrauterine device (IUD) within the study period;
• Anticipated elective procedure that is expected to require intensive treatment with VWF or FVIII for \>10 days during the study period;
• Patients with \>2 risk factors for VTE (risk factors are determined at discretion of treating physician) or recent history of thrombosis (i.e. within the last year).
• Patient concurrently receiving desmopressin (desmopressin cannot be taken concurrently with Wilate®, except for in the context of escalation treatment for excessive bleeding).
• Anticipated initiation of any new therapies for the treatment of heavy menstrual bleeding 3 weeks prior to enrollment

Sponsors & Collaborators

• Unity Health Toronto: lead

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B1W8, Canada

RECRUITING

MeSH Terms

Conditions

von Willebrand Diseases

Interventions

Factor VIII; von Willebrand Factor

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; Protein Precursors; Biological Factors

Central Study Contacts

St. Michael's Hospital

CONTACT

4168646060; empower@unityhealth.to

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2023
• First Posted: January 12, 2024
• Study Start: October 21, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 24, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)