Emicizumab treatment for severe Von Willebrand Disease and Hemophilia A

Emicizumab for Severe VON Willebrand Disease (VWD) and VWD/Hemophilia A

This study is testing if a new injection called Emicizumab can help people with severe Von Willebrand Disease or both Von Willebrand Disease and Hemophilia A prevent serious bleeding better than current treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 0 Years to 90 Years
• Sex: All
• Sponsor: Bleeding and Clotting Disorders Institute Peoria, Illinois (Academic / other)
• Drugs / interventions: emicizumab
• Locations: 12 sites (Orange, California and 11 other locations)
• Trial ID: NCT05500807 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of Emicizumab, a monoclonal bispecific antibody, for the prophylactic treatment of severe Von Willebrand Disease (VWD) and patients with both VWD and Hemophilia A. The study aims to provide a simplified subcutaneous treatment option, as current therapies often require intravenous administration. Participants will include individuals diagnosed with severe VWD or VWD with Hemophilia A, who will receive Emicizumab to prevent severe bleeding events. The trial will assess the effectiveness of this treatment compared to existing therapies.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals aged 2 and older diagnosed with severe Von Willebrand Disease type 3 or VWD with Hemophilia A.

Not a fit: Patients with mild forms of Von Willebrand Disease or those not requiring prophylaxis for bleeding events may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more convenient and effective option for managing severe bleeding in patients with Von Willebrand Disease and Hemophilia A.

How similar studies have performed: While Emicizumab has shown promise in treating Hemophilia A, its application for Von Willebrand Disease is still being explored, making this a novel approach.

Eligibility criteria

Inclusion Criteria:

* Signed informed consent
* Age 0 and older (infants weighing ≥3 kg)
* ability to comply with protocol in investigators judgement
* diagnosis of: severe VWD type 3, or VWD with VWF antigen, activity or collagen binding \</= 20 U/dl or variant VWD confirmed by genetic mutation and VWF ag, activity or CB \< 50 U/dl based on historical medical records of study site.
* diagnosis of VWD/hemophilia A defined as VWF:ag, activity or CB \<50 U/dl, and mild moderate or severe hemophilia A(defined by ISTH criteria) based on historical medical records of the study site.
* plan to be adherent to emicizumab prophylaxis during the study
* Patient's bleeding phenotype necessitating prophylaxis per treating provider recommendations.
* Patient on current prophylaxis for VWD or VWD/hemophilia A may enroll if they are currently on a non-emicizumab agent, and if it has been \> 18 months since last off-label dose of emicizumab, and are willing to discontinue current prophylaxis.
* For menstruating individuals: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year during the study period. A menstruating individual is considered to be of childbearing potential if they are post-menarchal, have not reached a postmenopausal state (12 continuous months of amenorrhea with no identified cause other than menopause), and have not undergone surgical sterilization (removal of ovaries and/or uterus).

Examples of highly effective contraceptive methods with a failure rate of \< 1% per year include proper use of combined oral or injected hormonal contraceptive, bilateral tubal ligation, male sterilization, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

* Patients and/or infants weighing \< 3 kg.
* Patients with low VWF or non-severe VWD (ie.not meeting the above criteria)
* Other concomitant bleeding disorders including coagulopathy from liver cirrhosis.
* Current treatment with emicizumab or emicizumab therapy in the previous 18 months.
* Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or current signs of thromboembolic disease
* Other conditions (e.g., certain autoimmune diseases, including, but not limited to diseases such as systemic lupus erythematosus, inflammatory bowel disease, and antiphospholipid syndrome) that may increase the risk of bleeding or thrombosis
* Patients who are at high risk for thrombotic microangiopathy (TMA; e.g., have a previous medical or family history of TMA), in the investigator's judgment
* Would refuse treatment with blood or blood products, if necessary.
* Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study
* Treatment with any of the following:

An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration before Study Day 1 A non-hemophilia-related investigational drug within the last 30 days or 5 halflives- before Study Day 1, whichever is longer An investigational drug concurrently

* History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection
* Pregnant or lactating, or intending to become pregnant during the study
* Women of childbearing potential must have a negative serum pregnancy test result within 7 days before Study Day 1
* Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
* Serious infection requiring oral or IV antibiotics within 30 days prior to screening

Where this trial is running

Orange, California and 11 other locations

• The Center for Comprehensive Care and Diagnosis of Inherited Blood Disorders (CIBD) — Orange, California, United States (Recruiting)
• Stanford University: Stanford Children's Health — Redwood City, California, United States (Recruiting)
• University of Miami - Miller School of Medicine — Coral Gables, Florida, United States (Recruiting)
• St. Joseph's Children's Hospital - Center for Bleeding and Clotting Disorders — Tampa, Florida, United States (Recruiting)
• Bleeding and Clotting Disorders Institute (BCDI) — Peoria, Illinois, United States (Recruiting)
• Innovative Hematology, Inc. (IHI) — Indianapolis, Indiana, United States (Recruiting)
• University of Michigan Medical School — Ann Arbor, Michigan, United States (Recruiting)
• Central Michigan University: Children's Hospital of Michigan — Mount Pleasant, Michigan, United States (Recruiting)
• Children's Mercy Hospital — Kansas City, Missouri, United States (Recruiting)
• Penn State College of Medicine — Hershey, Pennsylvania, United States (Recruiting)
• Washington Center for Bleeding Disorders — Seattle, Washington, United States (Recruiting)
• UW Health Comprehensive Program for Bleeding Disorders — Madison, Wisconsin, United States (Recruiting)

Study contacts

• Principal investigator: Jonathan C Roberts, MD — Bleeding and Clotting Disorders Institute
• Study coordinator: Megan L Woodbury, PhD

Conditions Von Willebrand Disease, Type 3; Concomitant VWD and Hemophilia