Hemophilia A with or without Factor VIII inhibitors MedDRA version: 28.0 Level: LLT Classification code 10053753 Term: Hemophilia A without inhibitors System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 28.0 Level: LLT Classification code 10053751 Term: Hemophilia A with anti factor VIII System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Hemlibra
Product Name: Emicizumab
Product Code: RO5534262
Pharmaceutical Form: Solution for injection
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for Arms A, B, and C: - Diagnosis of severe congenital hemophilia A or hemophilia A with FVIII inhibitors - Aged 12 years or older at the time of informed consent - Body weight =40 kilograms (kg) at the time of screening - Participants without FVIII inhibitors (3 kg at time of informed consent - Requires treatment with bypassing agents - Adequate hematologic, hepatic, and renal function - For female participants who are of childbearing potential, follow the same contraception criteria as listed above for Arms A, B, and C Are the trial subjects under 18? yes Number of subjects for this age range: 26 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 58 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: Exclusion Criteria for Arms A, B, and C: - Inherited or acquired bleeding disorder other than hemophilia A - At high risk for thrombotic microangiopathy, in the investigator’s judgment - History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the investigator’s judgment - Previous (in the past 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 that may increase risk of bleeding or thrombosis - History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection - Known human immuno-deficiency virus (HIV) infection with cluster of differentiation 4 (CD4) count 200 cells/mcL and meet all other criteria are eligible - Use of systemic immunomodulators at enrollment or planned use during the study, with the exception of anti-retroviral therapy - 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 investigator, preclude the participant’s safe participation in and completion of the study - Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study - Receipt of: 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 concurrently, within last 30 days or 5 half-lives, whichever is shorter - Pregnant or lactating, or intending to become pregnant during the study Exclusion Criteria for Arm D: - Inherited or acquired bleeding disorder other than hemophilia A - Ongoing (or plan to receive during the study) ITI therapy or prophylaxis treatment with FVIII - Previous (in the past 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 diseases that may increase risk of bleeding or thrombosis - History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection - Known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV) - At high risk for thrombotic microangiopathy, in the investigator’s judgment - Use of systemic immunomodulators at enrollment or planned use during the study - Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study - Inability (or unwillingness by caregiver) to receive (allow receipt of) blood or blood products (or any standard-of-care treatment for a life-threatening condition) - Receipt of: 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 concurrently, within last 30 days or 5 half-lives, whichever is shorter - Concurrent disease, treatment, or abnormality in clinical laboratory test
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the efficacy of prophylactic emicizumab (i.e., administered on a scheduled basis with the intent to prevent bleeds) compared with no prophylaxis in patients with hemophilia A - To evaluate the clinical effect of prophylactic emicizumab on the number of bleeds in pediatric patients;Secondary Objective: - To evaluate the efficacy of prophylactic emicizumab compared with no prophylaxis - To evaluate the overall safety of prophylactic emicizumab compared with no prophylaxis in patients with hemophilia A - To evaluate the overall safety of prophylactic emicizumab treatment in pediatric patients with hemophilia A and inhibitors - To characterize the exposure (through plasma concentration) of emicizumab in patients treated on QW or Q4W dosing;Primary end point(s): Annualized bleeding rate (ABR) for Treated Bleeds;Timepoint(s) of evaluation of this end point: From Baseline to at least 24 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Annualized bleeding rate (ABR) for All Bleeds 2) ABR for Treated Spontaneous Bleeds 3) ABR for Treated Joint Bleeds 4) ABR for Treated Target Joint Bleeds 5) Intra-Participant Comparison of the ABR for Treated Bleeds 6) Intra-Participant Comparison of the ABR for All Bleeds 7) Hemophilia A Quality of Life (Haem-A-QoL) Questionnaire Physical Health Domain Score at Week 25 in Participants =18 Years of Age 8) Haemo-QoL-SF Questionnaire Total Score at Baseline and Week 25 in Participants 12 to 17 Years of Age 9) European Quality of Life 5-Dimensions-5 Levels Questionnaire (EQ-5D-5L) Questionnaire Visual Analog Scale (VAS) Score at Week 25 10) EQ-5D-5L Index Utility Score at Week 25 11) Incidence and severity of adverse events 12) Incidence and severity of thromboembolic events 13) Incidence and severity of thrombotic microangiopathy 14) Incidence and severity of injection-site reactions 15) Incidence of adverse events leading to drug discontinuation 16) Incidence of severe hypersensitivity, anaphylaxis, or anaphylactoid reactions 17) Incidence of laboratory abnormalities 18) Changes in vital signs 19) Incidence of Anti-Emicizumab Antibodies 20) Trough Plasma Concentration of Emicizumab;Timepoint(s) of evaluation of this end point: 1) to 6) From Baseline to at least 24 weeks 7) to 10) Baseline and Week 25 11) to 17) From Baseline until end of study (up to 7 years, 4 months) 18) Baseline, Weeks 5, 25, 49, and at study completion 19) At prespecified timepoints from Baseline until end of study (up to 7 years, 4 months) 20) At prespecified timepoints from Baseline until end of study (up to 7 years, 4 months) | — |
Countries
China, Hong Kong, Malaysia, Thailand
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed