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

NCT ID: NCT06205095

Last Updated: 2024-12-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-21
• Study Completion Date: 2026-09-30

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

Detailed Description

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 explore assay sensitivity of the proposed efficacy clinical outcomes for a definitive randomized controlled trial.

For the first treatment period, patients will be randomized to receive either plasma derived von Willebrand factor:Factor VIII (pdVWF:FVIII) concentrate (plus standard of care) or placebo (plus standard of care) for VWD-associated heavy menstrual bleeding for 4 cycles, crossing over to the comparator treatment during the second treatment period. The first treatment period will be followed by a 1 cycle washout period when no study-based treatment will be delivered.

The main purpose of the pilot will be to evaluate viability and feasibility of the trial design, as well as to explore assay sensitivity to inform determination of the primary efficacy outcome for the definitive randomized trial which will evaluate the effect of prophylaxis with pdVWF:FVIII concentrate compared with placebo on HMB in women with VWD. A secondary objective is to conduct a preliminary assessment of the effect on clinical outcomes of 2-3 doses of prophylaxis with pdVWF:FVIII concentrate when provided on the first 4 days of menstruation compared with placebo.

Conditions

Von Willebrand Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

Lyophilized concentrate of human coagulation von Willebrand Factor and factor VIII

Intervention Type: 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.

Placebo and Standard Care

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Interventions

Lyophilized concentrate of human coagulation von Willebrand Factor and factor VIII

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.

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

Wilate

Eligibility Criteria

Inclusion Criteria

1. Patient capable of providing informed consent;

2. 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;

3. Modified PBAC score > 100 at screening;

4. Patients with a diagnosis of inherited von Willebrand disease (any type);

5. 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;

6. Patients willing to have an infusion administered by a nurse over the course of the study period;

7. Patients who agree to use only the feminine hygiene products supplied by the sponsor.

Exclusion Criteria

1. Diagnosed with any other known bleeding disorder;

2. Pregnancy or plans to become pregnant within the duration of the study;

3. Breastfeeding or plans to breastfeed within the duration of the study;

4. Known hypersensitivity reactions to human plasma-derived products or any ingredient in the formulation;

5. Known antibodies to VWF or FVIII;

6. Severe liver disease;

7. 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;

8. Anticipated elective procedure that is expected to require intensive treatment with VWF or FVIII for >10 days during the study period;

9. 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).

10. Patient concurrently receiving desmopressin (desmopressin cannot be taken concurrently with Wilate®, except for in the context of escalation treatment for excessive bleeding).

11. Anticipated initiation of any new therapies for the treatment of heavy menstrual bleeding 3 weeks prior to enrollment

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Unity Health Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

St. Michael's Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

St. Michael's Hospital

Role: CONTACT

Phone: 4168646060

Email: empower@unityhealth.to

Facility Contacts

Michelle Sholzberg

Role: primary

Other Identifiers

2.5

Identifier Type: -

Identifier Source: org_study_id