Severe or Moderate Hemophilia A MedDRA version: 20.0 Level: LLT Classification code 10053753 Term: Hemophilia A without inhibitors System Organ Class: 100000004850
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age >=13 and =65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: • Inherited or acquired bleeding disorder other than severe congenital hemophilia A (intrinsic FVIII level <1%) or moderate congenital hemophilia A (intrinsic FVIII level <=5%) without FVIII inhibitors who were previously prescribed prophylaxis for at least 24 weeks • Participants who have previously received emicizumab prophylaxis • Participants that plan to have joint replacement, joint procedure, synovectomy or synoviorthesis at screening • Participants who had joint replacement, joint procedure, synovectomy or synoviorthesis: – Less than 3 years ago OR – More than 3 years ago and are still experiencing pain in the joint For participants who had joint replacement, joint procedure, synovectomy or synoviorthesis more than 3 years ago who are not experiencing pain in the joint, the participant may be enrolled but the specific joint in which the procedure was conducted will be excluded from the study • Participants who have conditions other than hemophilia A that can affect joint health and structure (e.g., osteoarthritis) or with severely impaired mobility due to conditions other than hemophilia A • Participants with known reduced bone mineral density defined as clinically relevant vitamin D deficiency • Participants with pre-existing uncontrolled or unstable cardiovascular disease not receiving targeted medication or in a stable condition • Participants not eligible for MRI • History of illicit drug or alcohol abuse within 48 weeks prior to screening • Participants who are at high risk for thrombotic microangiopathy (TMA) • Previous (within the last 12 months) or current treatment for thromboembolic disease (with the exception of previous catheterassociated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease • Other conditions (e.g., 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 emicizumab injection • Planned surgery during the emicizumab loading dose phase • Known HIV infection not controlled by medication • Concomitant disease, condition, significant abnormality on screening evaluation or laboratory tests, or treatment that could interfere with the conduct of the study, or that would in the opinion of the investigator, pose an additional unacceptable risk in administering study drug to the participant • Receipt of any of the following: o An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration at screening o A non-hemophilia-related investigational drug within last 30 days or 5 half-lives at screening, whichever is shorter o Any other investigational drug currently being administered or planned to be administered • Inability to comply with the study protocol • Pregnant or breastfeeding, or intending to become pregnant during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 1. Joint status over time based on centrally reviewed Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) scores with a specific focus on the synovitis score in participants with synovitis 2. Clinical joint status over time based on the Hemophilia Joint Health Score (HJHS v2.1), excluding gait assessment 3. Joint status at screening and month 36 based on centrally reviewed International Prophylaxis Study Group (IPSG) score (with MRI) 4. Number of problem joints and proportion of problem joints, defined as joints having chronic joint pain and/or limited range of movement due to compromised joint integrity (i.e., chronic synovitis and/or hemophilic arthropathy) with or without persistent bleeding, over time 5. Number of target joint bleeds over time (target joints are defined as joints with >=3 bleeds occurring in the same joint during the last 24 weeks) 6. HRQoL, as assessed through use of the Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) Questionnaire over time with a focus on the following domains: risk perception of recreational activities, restrictions experienced in recreational activities, preoccupation with disease, impact of treatment burden on HRQoL, and pain severity 7. Change in the level of physical activity during the study as measured with a wearable activity tracker (Fitbit) 8. Change in daily step count, active minutes metabolic equivalents of tasks (METs), moderate to vigorous physical activity (MVPA; as per activity tracker default categorization), and type of physical activities 9. Change in the time and intensity level of physical activity as measured by the International Physical Activity Questionnaire Short Format (IPAQ-SF) 10. Number of all bleeds (i.e., those treated and untreated with FVIII), treated bleeds, spontaneous bleeds, joint bleeds, treated joint bleeds, and target joint bleeds (i.e., bleed rate) over time (ABR) as assessed through use of the Bleed and Medication Questionnaire ( | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Incidence and severity of adverse events, with severity determined according to World Health Organization (WHO) toxicity scale 2. Incidence of thromboembolic events 3. Incidence of thrombotic microangiopathy 4. Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events 5. Incidence and severity of injection-site reactions 6. Prevalence of anti-drug antibodies (ADAs) against emicizumab at baseline and incidence of ADAs against emicizumab during the study 7. Number and proportion of participants who develop anti-FVIII inhibitors (titer >=0.6 BU/mL) at specified timepoints ;Timepoint(s) of evaluation of this end point: 1-5. Until 24 weeks (Safety Follow-up) after the final dose of emicizumab 6. At Baseline (Day 1), Months 6, 12, 24 and 36 7. Up to 36 months | — |
Countries
Brazil, Canada, Germany, Hungary, Ireland, Italy, Morocco, Russian Federation, Serbia, Spain, Switzerland, Tunisia, Turkey, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed