Clinical trial NCT04188639: Emicizumab in Acquired Hemophilia A
Official title: Emicizumab in Patients With Acquired Hemophilia A: Multicenter, Single-arm, Open-label Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hemophilia A, Acquired
Keywords: acquired Hemophilia A
Factor VIII activity
Emicizumab
Lead sponsor: GWT-TUD GmbH
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
name: Hannover Medical School
First posted: 2019-12-06
Enrollment: 47
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 study is an international, multicenter, open-label, single arm, prospective clinical trial and will evaluate the efficacy of prophylactic emicizumab administered on a scheduled basis to prevent bleeds in patients with acquired hemophilia A (AHA).


Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with AHA based on a reduced FVIII activity (\<50 %) and positive FVIII inhibitor (\>0.6 BU/ml) (local laboratory) at time of diagnosis
* Signed informed consent form by the participant or a Person who is legally authorized to sign on behalf of the participant before any study specific tests or procedures are done
* Male or female patients aged 18 years or older at the time of informed consent
* Ability to understand and follow study-related instructions
* Current bleeds due to AHA at the time of screening

Exclusion Criteria:

* Congenital hemophilia A
* Partial or complete remission of AHA (defined as FVIII activity ≥ 50 % and no bleeding and no hemostatic therapy) at the time of screening
* Treatment with aPCC within the last 48 h before first study treatment or planned treatment with aPCC during the course of the study
* Treatment of AHA within the days before study enrollment with more than 100 mg prednisolone (or equivalent) per day or prednisolone for more than 2 days or with other immunosuppressive drugs (e.g. rituximab, cyclophosphamide). IST for other concomitant disorders (e.g. autoimmune disorders) is not an exclusion criterion and can be continued at the investigator's discrétion
* Therapy (current or planned during the emicizumab treatment period) with immunosuppressive or immune modulating drugs that were not already given on a regular basis before first diagnosis of AHA
* 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
* 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 local SmPC of emicizumab (see 16.1 Appendix I)
* 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
* Women of childbearing potential unless women who meet the following criteria:

  1. Post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum FSH \> 40 U/mL)
  2. Postoperatively (six weeks after bilateral ovariectomy with or without hysterectomy)
  3. Regular and correct use of a contraceptive method with error rate \<1% per year such as implants, depot injections, oral contraceptives or intrauterine devices
  4. Sexual abstinence
  5. Vasectomy of the partner
* Men of sexual activity with women of childbearing potential who are not willing to use an effective barrier method of contraception during and up to 3 months after the end of therapy
* Subject is in custody by order of an authority or a court of law
* Receipt of an investigational drug concurrently or within 5 half-lives before administration of the study drug

Primary outcomes:
measure: The number of clinically significant bleeds per patient-week until death or week 12 after starting emicizumab treatment, whatever occurs first
timeFrame: 12 weeks
Secondary outcomes:
measure: Incidence and severity of adverse events, thromboembolic events, thrombotic microangiopathy in the 12 weeks after starting emicizumab
timeFrame: 12 weeks
measure: Incidence of mortality and cause of death in the 24 weeks after starting emicizumab treatment
timeFrame: 24 weeks
measure: Days of treatment with and total dose of bypassing agents (recombinant factor VIIa, activated prothrombin complex concentrate) or recombinant porcine factor VIII (susoctocag alfa) or other factor VIII concentrates
timeFrame: 24 weeks
measure: Days in hospital during 12 weeks of emicizumab treatment
timeFrame: 12 weeks
measure: Number of patients achieving partial remission in the 24 weeks after starting emicizumab treatment
timeFrame: 24 weeks
measure: Bleeding-free survival in the 12 weeks after starting emicizumab treatment
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Medizinische Universität Wien, Hämatologie/Hämostaseologie
state: Niederösterreich
city: Graz
country: Austria
facility: Medizinische Universitätsklinik Graz
state: Steiermark
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg, Universitätsklinikum der PMU, Innere Med. III
city: München
country: Germany
facility: LMU Klinikum, Hämophiliezentrum Erwachsene/Transfusionsmedizin
state: Bayern
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Innere Med. III - Studienzentrale
state: Bayern
city: Berlin-Friedrichshain
country: Germany
facility: Vivantes Klinikum im Friedrichshain, Angiologie/Hämostaseologie
state: Berlin
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt, Hämostaseologie/Hämophiliezentrum
state: Hessen
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen und Marburg
state: Hessen
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Hämatologie/Hämostaseologie
state: Niedersachsen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn, Hämatologie/Transfusionsmedizin/Hämophilie
state: Nordrhein-Westfalen
city: Homburg / Saar
country: Germany
facility: Universitätsklinikum des Saarlandes, Institut für Klinische Hämostaseologie und Transfusionsmedizin
state: Saarland
city: Dresden
country: Germany
facility: Universitätsklinikum Dresden, Med. Poliklinik I
state: Sachsen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I, Bereich Hämostaseologie
state: Sachsen
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Klinische Chemie/Gerinnungszentrum
state: Schleswig-Holstein
city: Jena
country: Germany
facility: Universitätsklinikum Jena, Klinik für Innere Medizin II
state: Thüringen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Med. Klinik II/Gerinnungsambulanz
Study officials:
affiliation: Hannover Medical School
name: Andreas Tiede, Prof. Dr.
role: STUDY_DIRECTOR
References: