Hemophilia A with Inhibitors MedDRA version: 18.1 Level: LLT Classification code 10053753 Term: Hemophilia A without inhibitors System Organ Class: 100000004850
Conditions
Sponsors
Roche Farma, S.A., que representa en España a F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Children 3 kg - Caregivers must have the willingness and ability to comply with all study procedures - Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor - Requires treatment with bypassing agents - For patients >= 2 years of age: if on episodic bypassing agent regimen annualized bleeding rate (ABR) of >=6 ; or if on prophylactic bypassing agent regimen inadequately controlled or central venous access device (CVAD) placement medically not feasible or deemed unsafe - For patients =100 x 10*9 cells/Liter (L) and hemoglobin >= 8 gram (g)/deciliter (dL) (4.97 millimoles/L) at the time of screening - Adequate hepatic and renal function - Female patients of childbearing potential who have negative serum pregnancy test result and an agreement to remain abstinent or use contraceptive methods specified in the study Are the trial subjects under 18? yes Number of subjects for this age range: 40 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Inherited or acquired bleeding disorder other than hemophilia A - Ongoing or plan to receive immune tolerance induction (ITI) therapy or prophylaxis treatment with FVIII during the study. Patients awaiting initiation of ITI will be eligible and patients in whom ITI has failed will be eligible with a 72-hour washout period prior to the first emicizumab administration - 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 (i.e., certain autoimmune diseases [e.g., systemic lupus erythematosus], cardiovascular disease) that may increase risk of bleeding or thrombosis - Known infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus - Use of systemic immunomodulators (e.g., interferon or corticosteroids) at enrolment or planned use during the study period - Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: There is no formal hypothesis testing in the study. Efficacy ? To evaluate clinical effect of prophylactic emicizumab on number of bleeds over time (bleed rate) ? To characterize efficacy of up-titration on both intra-patient and population level, also on the basis of the number of bleeds over time ? To evaluate Health-Related Quality of Life (HRQoL) of children 8-17 years of age according to Hemophilia-Specific Quality of Life Index (Haemo-QoL) Short Form (SF) (completed by patients) ? To evaluate proxy-reported HRQoL and aspects of caregiver burden using the Adapted inhibitor-specific questionnaire for the assessment of health-related quality of life (InhibQoL) including aspects of caregiver burden questionnaire for all children (completed by caregivers) ? To assess number of days away from day care/preschool/school and days hospitalized;Secondary Objective: There is no formal hypothesis testing in the study. Safety: ? To evaluate overall safety of emicizumab Pharmacokinetic: ? To characterize the exposure [minimum observed analyte concentration (Ctrough)] of emicizumab in patients prior to drug administration Pharmacodynamics: ? To assess potential pharmacodynamic (PD) biomarkers of emicizumab, including but not limited to activated partial thromboplastin time (aPTT) and FVIII activity;Primary end point(s): Efficacy: 1. Number of bleeds over time 2. An up-titration on both, an intra-patient and population level 3. Comparison between historical and on study treatment period for bleed over time 4. HRQoL of children 8-17 years of age according to Haemo QoL SF (completed by patients) 5. Proxy-reported HRQoL and aspects of caregiver burden using the adapted InhibQoL Including aspects of caregiver burden questionnaire for all children (completed by caregivers) 6. Number of days away from day care/preschool/school and days hospitalized;Timepoint(s) of evaluation of this end point: Efficacy: 1-3. Up to 52 weeks 4-6. Weeks 1, 13, 25, 37, 49, and every 2 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety: 1. Incidence and severity of adverse events 2. Incidence and severity of thromboembolic events 3. Changes in physical examination findings and vital signs 4. Incidence of laboratory abnormalities 5. Incidence and severity of injection-site reactions 6. Incidence of adverse events leading to drug discontinuation 7. Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events 8. Incidence and clinical significance of anti-emicizumab antibodies Pharmacokinetic: 1. Ctrough of emicizumab Pharmacodynamics: 1. included but not limited to aPTT FVIII activity;Timepoint(s) of evaluation of this end point: Safety: 1-7. Up to 128 weeks 8. Weeks 1, 5, 17, 33, 49, every 12 weeks starting from Week 57 up to Week 128 Pharmacokinetic: 1. Weeks 1, 2, 3, 4, 5, 7, 9, 13, 17, 21, 25, 29, 33, 37, 41, 49, and every 12 weeks from Week 57 up to Week 128 Pharmacodynamics: 1. Weeks 1, 3, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 49, and every 12 weeks from Week 57 up to Week 128 | — |
Countries
Costa Rica, France, Germany, Italy, Japan, South Africa, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed