Clinical trial NCT05345197: Emicizumab in Patients With Acquired Hemophilia A
Official title: Emicizumab in Patients With Acquired Hemophilia A: Multicenter, Single-arm, Open-label Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acquired Hemophilia A
Keywords: Acquire Hemophilia A
emicizumab
AHA
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2022-04-25
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase II multicenter open-label, single-arm prospective study to evaluate the efficacy of prophylactic emicizumab administered on a scheduled basis to prevent bleeds in patients with acquired hemophilia A (AHA).

Detailed description: Patients with AHA who are eligible will receive two loading doses of the study drug, emicizumab (6mg/kg on day 1 and 3 mg/kg on day 2) followed by once weekly subcutaneous emicizumab (1.5 mg/kg). Immunosuppression will be given concurrently as per investigator discretion. The primary endpoint (bleed rate) will be assessed after 12 weeks on study drug. If partial remission of the AHA has not been achieved, an additional 12 weeks of study drug may be given. A historical cohort and a study conducted in parallel in Germany (NCT04188639) will serve as control groups for evaluation of secondary endpoints provided the study cohort are comparable.

Eligibility criteria: Inclusion Criteria:

* Signed Informed Consent/Assent Form
* Age ≥18 years at time of signing Informed Consent Form
* Ability to comply with the study protocol, in the investigator's judgment
* Diagnosis of AHA based on a reduced FVIII activity (\<50 %) and positive FVIII inhibitor (\>0.6 BU/ml) at screening (local laboratory)
* Current bleeding due to AHA at the time of screening
* Plan to be adherent to emicizumab prophylaxis during the study
* For women of childbearing potential who meet the following criteria:
* Refrain from heterosexual intercourse or use contraceptive methods that result in a failure rate of \<1% per year during the study period A woman with ≥ 12 continuous months of amenorrhea with no identified cause other than menopause and has not undergone surgical sterilization (removal of ovaries and/or uterus). use of combined oral or injected hormonal contraceptive, bilateral tubal ligation, male sterilization, hormone- releasing intrauterine devices, and copper intrauterine devices.

Exclusion Criteria:

* Congenital hemophilia A
* Treatment with aPCC within the last 24 hours before first study treatment or planned treatment with aPCC during the course of the study
* Known positive lupus anticoagulant at the time of screening
* Severe uncontrolled infection at the time of screening
* Signs of active disseminated intravascular coagulation at the time of screening -
* Emicizumab ⎯ AHA Emi Version 1.0 20
* Current treatment for thromboembolic disease or signs of current thromboembolic disease at time of screening
* Patients who are at high risk for TMA (e.g., have a previous medical or family history of TMA), in the investigator's judgment
* Known severe congenital or acquired thrombophilia
* Life expectancy \<3 months at the time of screening
* Other conditions that substantially increase risk of bleeding or thrombosis by the discretion of the investigator
* Contraindications according to the Investigator's Brochure of emicizumab
* Current treatment with emicizumab at time of screening
* History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection by the discretion of the investigator
* Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose additional risk, or would, in the opinion of the local investigator, preclude the patient's safe participation in and completion of the study
* Addiction or other diseases that preclude the patient from appropriately assessing the nature and scope as well as possible consequences of the clinical study by the discretion of the investigator
* Pregnant or breast-feeding women
* Would refuse treatment with blood or blood products, if necessary.
* Subject is in custody by order of an authority or a court of law
* 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 half-lives- 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

Primary outcomes:
measure: Primary Outcome Meassure
timeFrame: 12 weeks
Secondary outcomes:
measure: Incidence and severity of adverse events
timeFrame: duration of entire study
measure: Days of treatment with additional hemostatic agent
timeFrame: 12 weeks
measure: Remission Rate
timeFrame: 1 to 24 weeks
measure: Hospitalizations
timeFrame: 12 weeks
measure: Total dose of additional hemostatic agent
timeFrame: 12 weeks
Other outcomes:
measure: Comparison of historic GTH-AH 01/2020 cohort/ Number of clinically significant bleeds
timeFrame: 12 to 24 weeks
measure: Comparison to a parallel German study cohort/ Number of clinically significant bleeds
timeFrame: 12 to 24 weeks
Locations:
city: San Diego
country: United States
facility: UCSD Hemophilia and Thrombosis Treatment Center
state: California
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Peoria
country: United States
facility: Bleeding and Clotting Disorders Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center, Inc.
state: Indiana
city: New Orleans
country: United States
facility: Tulane University
state: Louisiana
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Penn Blood Disorders Program, Hospital of the University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Hemophilia Center of Western Pennsylvania
state: Pennsylvania
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Charlottesville
country: United States
facility: UVA Comprehensive Cancer Center
state: Virginia
city: Seattle
country: United States
facility: Washington Center for Bleeding Disorders
state: Washington
city: Milwaukee
country: United States
facility: Versiti Inc.
state: Wisconsin
Study officials:
affiliation: University of Washington
name: Rebecca Kruse-Jarres, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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