Emicizumab in Acquired Hemophilia A

• ClinicalTrials.gov Identifier: NCT04188639
• Recruitment Status: Active, not recruiting
• First Posted: December 6, 2019
• Last Update Posted: June 29, 2022
• Sponsor: GWT-TUD GmbH
• Collaborators: Hoffmann-La Roche; Hannover Medical School
• Information provided by (Responsible Party): GWT-TUD GmbH

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Hemophilia A, Acquired	Drug: Emicizumab Injection	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 47 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Emicizumab in Patients With Acquired Hemophilia A: Multicenter, Single-arm, Open-label Clinical Trial
• Actual Study Start Date: March 23, 2021
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment with emicizumab	Drug: Emicizumab Injection; All eligible patients with AHA will receive the same study medication consisting of once weekly subcutaneous emicizumab. For each subject, the maximal duration of the study will be 24 weeks including 12 weeks treatment with emicizumab and 12 weeks follow-up with Immunosuppressive therapy (IST) at the investigators discretion.; Other Name: Hemlibra (R)

Outcome Measures

Primary Outcome Measures :

1. The number of clinically significant bleeds per patient-week until death or week 12 after starting emicizumab treatment, whatever occurs first [ Time Frame: 12 weeks ]

Secondary Outcome Measures :

1. Incidence and severity of adverse events, thromboembolic events, thrombotic microangiopathy in the 12 weeks after starting emicizumab [ Time Frame: 12 weeks ]
2. Incidence of mortality and cause of death in the 24 weeks after starting emicizumab treatment [ Time Frame: 24 weeks ]
3. 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 [ Time Frame: 24 weeks ]
4. Days in hospital during 12 weeks of emicizumab treatment [ Time Frame: 12 weeks ]
5. Number of patients achieving partial remission in the 24 weeks after starting emicizumab treatment [ Time Frame: 24 weeks ]
6. Bleeding-free survival in the 12 weeks after starting emicizumab treatment [ Time Frame: 12 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Austria

Medizinische Universität Wien, Hämatologie/Hämostaseologie

Wien, Niederösterreich, Austria, 1090

Medizinische Universitätsklinik Graz

Graz, Steiermark, Austria, 8036

Landeskrankenhaus Salzburg, Universitätsklinikum der PMU, Innere Med. III

Salzburg, Austria, 5020

Germany

LMU Klinikum, Hämophiliezentrum Erwachsene/Transfusionsmedizin

München, Bayern, Germany, 80336

Universitätsklinikum Regensburg, Innere Med. III - Studienzentrale

Regensburg, Bayern, Germany, 93052

Vivantes Klinikum im Friedrichshain, Angiologie/Hämostaseologie

Berlin-Friedrichshain, Berlin, Germany, 10249

Universitätsklinikum Frankfurt, Hämostaseologie/Hämophiliezentrum

Frankfurt, Hessen, Germany, 60590

Universitätsklinikum Gießen und Marburg

Gießen, Hessen, Germany, 35392

Medizinische Hochschule Hannover, Hämatologie/Hämostaseologie

Hannover, Niedersachsen, Germany, 30625

Universitätsklinikum Bonn, Hämatologie/Transfusionsmedizin/Hämophilie

Bonn, Nordrhein-Westfalen, Germany, 53127

Universitätsklinikum des Saarlandes, Institut für Klinische Hämostaseologie und Transfusionsmedizin

Homburg / Saar, Saarland, Germany, 66421

Universitätsklinikum Dresden, Med. Poliklinik I

Dresden, Sachsen, Germany, 01307

Universitätsklinikum Leipzig, Medizinische Klinik und Poliklinik I, Bereich Hämostaseologie

Leipzig, Sachsen, Germany, 04103

Universitätsklinikum Schleswig-Holstein, Klinische Chemie/Gerinnungszentrum

Kiel, Schleswig-Holstein, Germany, 24105

Universitätsklinikum Jena, Klinik für Innere Medizin II

Jena, Thüringen, Germany, 07747

Universitätsklinikum Hamburg-Eppendorf, Med. Klinik II/Gerinnungsambulanz

Hamburg, Germany, 20246

Sponsors and Collaborators

GWT-TUD GmbH

Hoffmann-La Roche

Hannover Medical School

Investigators

• Study Director: Andreas Tiede, Prof. Dr.; Hannover Medical School

More Information

• Responsible Party: GWT-TUD GmbH
• ClinicalTrials.gov Identifier: NCT04188639
• Other Study ID Numbers: AHA-EMI (MO41153)
• First Posted: December 6, 2019
• Last Update Posted: June 29, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GWT-TUD GmbH:

acquired Hemophilia A; Factor VIII activity; Emicizumab

Additional relevant MeSH terms:

Hemophilia A; Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn