Factor VIII Deficiency, Congenital Clinical Trial
Official title:
Prospective, Single-Arm, Open-Label Use of Hemlibra (Emicizumab) in the Treatment of Mild Hemophilia A
This is a single arm, phase 4, prospective, open-label, United States single-center study to determine the hemostatic characteristics of Hemlibra (emicizumab) as measured by coagulation laboratory parameters in the mild hemophilia A male patient population with endogenous altered FVIII (baseline FVIII activity of >5% to 30%). The safety and hemostatic efficacy of Hemlibra (emicizumab) in this patient population will be investigated. Secondary outcomes will assess changes in joint health and quality of life in treated patients.
Status | Recruiting |
Enrollment | 20 |
Est. completion date | July 2027 |
Est. primary completion date | July 2025 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 5 Years to 45 Years |
Eligibility | Inclusion Criteria: - Signed informed consent form from the subject, parent or guardian - Male sex - Diagnosis of mild congenital hemophilia A (baseline FVIII level of >5% to 30%) without a current FVIII inhibitor or a history of FVIII inhibitor - Any number of FVIII exposure days, including PUPs - BMI <30 - Age =5 years to =45 years - Medical documentation of bleeding events, outcomes and hemostatic product usage for 12 months prior to study enrollment - Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the health-related questionnaires, activity tracking, and bleed diaries, using systems provided during the study - Willingness to undergo a Stimate/DDAVP challenge (only if the subject reports no adverse event associated with prior Stimate [DDAVP/desmopressin acetate] use); Stimate/DDAVP challenge will not be performed if the patient has a documented history of lack of response as defined by an increase of FVIII < 2 times baseline level - Adequate hepatic function, defined as total bilirubin =1.5 × age-adapted upper limit of normal (ULN) (excluding Gilbert's syndrome) and both AST and ALT =3 × age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis - Adequate hematologic function, defined as a platelet count =100,000/µL and a PT=1.5 times the ULN at the time of screening - Adequate renal function, defined as serum creatinine =2.5 × age-adapted ULN and creatinine clearance =30 mL/min by Cockcroft-Gault formula Exclusion Criteria: - Inherited or acquired bleeding disorder other than mild congenital hemophilia A (baseline FVIII level of >5% to 30%) - Any bleeding disorder other than or in addition to mild hemophilia A - Current or prior inhibitor to FVIII (any titer) - Female sex - History of CVD, risk of CVD by the ASCVD risk estimator (defined as a subject having >20% risk of a cardiovascular event within the next 10 years if the subject is =20 years of age) and/or a history of ischemic heart disease [ICD codes 120-125] - High risk for TMA (eg, have a previous medical or family history of TMA), in the Study Investigator's judgment - History of illicit drug or alcohol abuse by report or in the Study Investigator's judgment - Previous (within the last 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 signs of thromboembolic disease - Other conditions (eg, certain autoimmune diseases) that may currently increase the risk of bleeding or thrombosis - History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the Hemlibra (emicizumab) injection - Known HIV infection with CD4 counts <200 cells/µL. HIV infection with CD4 counts =200 cells/µL permitted - Use of systemic immunomodulators (eg, interferon) at enrollment or planned use during the study, with the exception of anti-retroviral therapy - Concomitant disease, condition, significant abnormality on screening evaluations or laboratory tests, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the Study Investigator, pose an additional unacceptable risk in administering study drug to the patient - Receipt of any of the following: - Hemlibra (emicizumab) in a prior investigational study - An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration - A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter - Any other investigational drug currently being administered or planned to be administered - Inability to comply with the study protocol in the opinion of the Study Investigator |
Country | Name | City | State |
---|---|---|---|
United States | Indiana Hemophila @Thrombosis Center | Indianapolis | Indiana |
Lead Sponsor | Collaborator |
---|---|
Indiana Hemophilia &Thrombosis Center, Inc. | Genentech, Inc. |
United States,
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* Note: There are 24 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Interaction of Hemlibra (emicizumab) binding with endogenous altered FVIII protein in an individual with mild hemophilia A and the combined effect on thrombin generation and hemostatic characteristics | Change in FVIII human chromogenic activity, FVIII bovine chromogenic activity, and Thrombin Generation Assay relatively to one another | Before treatment, month 4, month 7, and month 13 | |
Secondary | Breakthrough bleeds | Rate of bleeding events requiring alternate hemostatic therapy | Through study completion, up to 35 months | |
Secondary | Factor VIII alteration and coagulation | Relationship between Factor VIII alteration and coagulation laboratory parameters | Before treatment, month 4, month 7, and month 13 | |
Secondary | Change from baseline joint disease annually | Baseline presence of joint disease through 6 joint POC MSKUS and its stabilization, resolution, or progression | Through study completion annually, up to 35 months | |
Secondary | AE, SAE, and ADA | Rate of adverse events (AEs) and serious adverse events (SAEs) including lack of efficacy and development of neutralizing anti-drug antibodies (ADA) | Through study completion annually, up to 35 months | |
Secondary | ADA development | Number of participants with development of neutralizing anti-drug antibodies (ADA) if it occurs | ADA assay at month 4, month 7, month 13, and end of study participation | |
Secondary | Alternate hemostatic therapies with surgery | Rate of use of alternate hemostatic therapies (eg, FVIII, Stimate/DDAVP, etc) during surgeries and procedures and their hemostatic efficacy to prevent or treat bleeding | At time of patient's surgery if applicable | |
Secondary | Change in quality of life: questionnaire | Change in quality of life as measured by Haemo-QoL (haemophilia-specific quality of life questionnaire) if <17 years of age; and Haem-A-QoL-A (haemophilia-specific quality of life questionnaire for adults) if =17 years of age. Scores range from 0 to 100, with higher scores indicating a lower quality of life. | Before treatment, Day 0, Day 7, Day 14, Day 21, month 13, month 25 | |
Secondary | Change in activity: questionnaire | Change in activity level as measured by CATCH (Comprehensive Assessment Tool of Challenges in Hemophilia) questionnaire. Change from baseline in the daily activity risk perception and impact domain score over time. This is not a scaled assessment. | Before treatment, Day 0, Day 7, Day 14, Day 21, month 13, month 25 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
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