E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe hemophilia A without factor VIII inhibitors |
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E.1.1.1 | Medical condition in easily understood language |
Hemophilia A is deficiency in clotting factor VIII (FVIII), which causes increased bleeding. Severe hemophilia A can occur after injury or spontaneously, often in joints and muscles. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053753 |
E.1.2 | Term | Hemophilia A without inhibitors |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the impact of emicizumab on aspects of health-related quality of life (HRQoL) |
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E.2.2 | Secondary objectives of the trial |
• To evaluate impact of emicizumab on physical activity (PA) • To evaluate the impact of emicizumab on joint health • To evaluate the impact of emicizumab on bleeds, and compared with previous factor VIII (FVIII) prophylaxis • To evaluate the impact of emicizumab on health status • To assess the treatment preference for emicizumab according to the emicizumab preference (EmiPref) questionnaire • To evaluate the impact of emicizumab on caregiver burden • To evaluate the safety of emicizumab in patients with severe hemophilia A without FVIII inhibitors
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males with diagnosis of severe congenital hemophilia A without FVIII inhibitor (FVIII level <1%) • At least 150 exposure days of FVIII and at least 24 weeks of FVIII prophylaxis prior to enrollment • Age between 12 and 61 years at the time of signing the Informed Consent Form • Able to comply with the study protocol, in the investigator’s judgment • Having completed Study MO42590 (non-interventional) • Willingness and ability to comply with scheduled visits, treatment plans, use an activity tracker and other study procedures, including the completion of questionnaires and a bleed and medication diary using an ePRO app. For patients >=12-17 years the hemophilia associated caregiver burden scale (HEMOCAB) questionnaire will be answered by the caregiver • Patients with previous inhibitors should have no documented inhibitors to FVIII (i.e., <0.6 BU/mL), since the last 76 weeks prior (+ 8 weeks window if applicable) to enrollment • Patients with previous inhibitors should have a normal FVIII half-life, which could be measured up to 76 weeks (+ 8 weeks window if applicable) before enrollment • The investigator’s judgment of medical need of change of treatment that could include, however not limited to; poor venous access, high treatment burden, and compliance issues • To have at least one treated joint or muscle bleeding episode in the last 76 weeks (+ 8 weeks window if applicable) |
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E.4 | Principal exclusion criteria |
• Patients with FVIII inhibitors • Inherited or acquired bleeding disorder other than hemophilia A • Previous (in the past 18 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 (e.g., certain autoimmune diseases) that may increase the risk of bleeding or thrombosis according to investigator’s clinical judgment • History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection • Inability to comply with the study protocol in the opinion of the investigator • Planned surgery (excluding, minor procedures such as tooth extraction or incision and drainage) during the study • Current drug or alcohol dependence • Female with severe hemophilia A |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from baseline in the following domains: risk perception of recreational activities, restrictions experienced in recreational activities, preoccupation with disease, impact of treatment burden on HRQoL, and pain sevirity as measured by the Comprehensive Assessment Tool of Challenges in Hemophilia (CATCH) questionnaire |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1 Baseline (Week 24 (MO42590)), Weeks 25 and 49 |
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E.5.2 | Secondary end point(s) |
1. Level of PA during study measured with an activity tracker 2. Time and intensity levels of PA as measured by the international physical activity questionnaire-short form (IPAQ-SF) 3. Levels of PA measured with activity tracker compared with data collected from the preceding non-interventional standard of care study MO42590 4. Hemophilia early arthropathy detection with ultrasound (HEAD-US) 5. Hemophilia joint health score 2.1 (HJHS) 6. Number of treated bleeds over time in patients 7. Percentage of patients with zero-treated bleeds 8. Number of all bleeds over time in patients 9. Number of treated spontaneous or traumatic bleeds over time in patients 10. Number of treated joint bleeds over time in patients 11. Number of treated target joint bleeds over time in patients treated with emicizumab 12. Number of FVIII doses and total amount of units to treat a breakthrough bleed in patients treated with emicizumab 13. Change from baseline in health status as measured by the euroQoL five-dimension-five level questionnaire (EQ-5D-5L) 14. Patient preference for the emicizumab regimen as measured by the emicizumab preference (EmiPref) questionnaire 15. Change from baseline in caregiver burden using Hemophilia Associated Caregiver Burden (HEMOCAB) scale (ages 12-17) 16. Incidence and severity of adverse events
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Weeks 9-16, 25-32, and 41-48 2. Baseline (Week 1), Weeks 13, 25, 37 and 49 3. Baseline Week 1-8 (MO42590), Weeks 17-24 (MO42590), Week 25-32 and Weeks 41-48 4-5. Baseline (Week 1) and Weeks 49 6-12. Up to 49 Weeks 13. Baseline (Week 1), Weeks 25 and 49 14. Weeks 25 and 49 15. Baseline (Week 1) and Week 49 16. Up to Week 49
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
- Evaluation of the impact of emicizumab on aspects of health-related quality of life. - Impact of emicizumab on caregiver burden |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |