Dynamics of the Anti-factor VIII Antibody Signature During Treatment With Emicizumab

Severe Hemophilia A Clinical Trial

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Official title:

Dynamics of the Anti-factor VIII Antibody Signature During Treatment With Emicizumab

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05802836
• Other study ID #: ML44394
• Secondary ID: DRKS00031196
• Status: Recruiting
• Start date: April 26, 2023
• Est. completion date: December 2029

Study information

• Verified date: July 2023
• Source: Goethe University
• Contact: Stephan Schultze-Strasser, Dr.
• Phone: +496963016998
• Email: stephan.schultze-strasser[@]kgu.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to learn about the changes of antibodies and inhibitors against the coagulation factor VIII in patients with severe hemophilia A receiving emicizumab therapy. No additional visits or procedures are planned. Patients in this study will continue to receive their routine care and analysis will be done from left over samples from routine visits.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2029
• Est. primary completion date: December 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Severe congenital hemophilia A (CHA)
• Treatment with emicizumab irrespective of any other treatment
• Informed consent

Exclusion Criteria:

• No therapy with emicizumab
• Immunosuppressive therapy
• HIV-infection with CD4 (cluster of differentiation 4) cells <200/µl

Related Conditions & MeSH terms

• Hemophilia A
• Severe Hemophilia A
• Severe Hemophilia A With Inhibitor

Intervention

Other:
• no interventions
no intervention, only 3 different patients groups

Locations

Country	Name	City	State
Germany	University Hospital Frankfurt, Goethe University	Frankfurt	Hessen

Sponsors (3)

Lead Sponsor	Collaborator
Christoph Königs	Chugai Pharma Germany GmbH, Roche Pharma AG

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	FVIII inhibitor development in inhibitor negative subjects	Rate of FVIII inhibitor development during three years of emicizumab prophylaxis in inhibitor negative subjects. Assessed with Bethesda Assay (BU/ml). Number of patients who develop an FVIII inhibitor within the study period, but were FVIII inhibitor negative at start of the study.	3 years
Primary	FVIII antibody development in inhibitor negative subjects	Rate of FVIII antibody development during three years of emicizumab prophylaxis in inhibitor negative subjects. FVIII anti drug antibody (ADA) is assessed by FVIII specific ELISA (OD=Optical Density). Number of patients who develop an FVIII antibody (ADA) within the study period, but were FVIII inhibitor negative at start of the study.	3 years
Primary	FVIII inhibitor disappearance in inhibitor positive subjects	Rate of FVIII inhibitor disappearance during three years of emicizumab prophylaxis in inhibitor positive subjects. Assessed with Bethesda Assay (BU/ml). Number of patients who loose an FVIII inhibitor within the study period, but were FVIII inhibitor positive at start of the study.	3 years
Primary	FVIII antibody disappearance in inhibitor positive subjects	Rate of FVIII antibody disappearance during three years of emicizumab prophylaxis in inhibitor positive subjects. FVIII anti drug antibody (ADA) is assessed by FVIII specific ELISA (OD=Optical Density). Number of patients who develop an FVIII antibody within the study period, but were FVIII inhibitor positive at start of the study.	3 years
Secondary	Anti-FVIII inhibitor development	Anti-FVIII inhibitor development (median BU/ml) over time. Assessed with Bethesda Assay (BU/ml). Description of inhibitor development in the different patient groups within the study period. Cut off is 0,6 BU/ml.	3 years
Secondary	Anti-FVIII antibody development	Anti-FVIII antibody development (median arbitrary units, OD) over time. Description of antibody development in the different patient groups within the study period.	3 years
Secondary	Time to negative inhibitor titers	Time to negative inhibitor titers. Assessed with Bethesda Assay (BU/ml). Description of the Time (days) observed for FVIII inhibitor disappearance within the study period in the patient groups. Cut off for inhibitor titer is 0,6 BU/ml.	3 years
Secondary	Treatment of bleeds	Description of the use of FVIII and/or Bypassing agents treatment in addition to Emicizumab treatment in case of bleeds.	3 years
Secondary	Response to treatment	Classification of bleeds as Effective, Partially Effective, Ineffective. Defined as: Effective: Bleeding episode responded to the usual number of injections or dose of FVIII as expected by the treating physician; Partially Effective: The bleeding episode responded with a higher number of injections and/or dose as expected by the treating physician; Ineffective: Routine failure to control hemostasis or hemostatic control required additional agents	3 years
Secondary	Quality of the antibody response (FVIII epitopes)	Description of the location of FVIII epitopes over time, assessed by epitope mapping technique (ELISA)	3 years
Secondary	Quality of the antibody response (IgG subclasses)	Description of a potential immune response over time, assessed by IgG subclass determination (ELISA).	3 years