E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acquired Hemophilia A (AHA) |
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E.1.1.1 | Medical condition in easily understood language |
aquired bleeding disorder |
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E.1.1.2 | Therapeutic area | Body processes [G] - Immune system processes [G12] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053761 |
E.1.2 | Term | Acquired hemophilia with anti FVIII, XI, or XIII |
E.1.2 | System Organ Class | 100000004851 |
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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 | 10053760 |
E.1.2 | Term | Acquired hemophilia |
E.1.2 | System Organ Class | 100000004851 |
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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 |
The primary objective of the present study is to evaluate the efficacy of prophylactic emicizumab administered on a scheduled basis to prevent bleeds in patients with acquired hemophilia A (AHA). |
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E.2.2 | Secondary objectives of the trial |
- To study the safety of emicizumab in patients with AHA - To compare bleeding and adverse events with the historic GTH-AH 01/2010 cohort - To compare bleeding and adverse events with a parallel US study - To evaluate the pharmacokinetics (PK) of emicizumab in patients with AHA
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Patients diagnosed with AHA based on a reduced FVIII activity (<50 %) and positive FVIII inhibitor (>0.6 BU/ml) at the time of diagnosis (local laboratory) 2) Signed informed consent form by the participant or a person who is legally authorized to sign on behalf of the participant before any study specific tests or procedures 3) Male or female patients aged 18 years or older at the time of informed consent 4) Ability to understand and follow study-related instructions 5) Current bleeds due to AHA at the time of screening
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E.4 | Principal exclusion criteria |
1) Congenital hemophilia A 2) Partial or complete remission of AHA (defined as FVIII:C =50% and no bleeding and no hemostatic therapy) at the time of screening 3) Treatment with aPCC within the last 48 h before first study treatment or planned treatment with aPCC during the course of the study 4) Treatment of AHA within the days before study enrollment with more than 100 mg prednisolone (or equivalent) per day or prednisolone for more than 2 days or with other immunosuppressive drugs (e.g. rituximab, cyclophosphamide). IST for other concomitant disorders (e.g. autoimmune disorders) is not an exclusion criterion and can be continued at the investigator’s discretion. 5) Therapy (current or planned during the emicizumab treatment period) with immunosuppressive or immune modulating drugs that were not already given on a regular basis before first diagnosis of AHA 6) Positive lupus anticoagulant at the time of screening 7) Severe uncontrolled infection at the time of screening 8) Signs of active disseminated intravascular coagulation at the time of screening 9) Current treatment for thromboembolic disease or signs of current thromboembolic disease at time of screening 10) Patients who are at high risk for TMA (e.g., have a previous medical or family history of TMA), in the investigator’s judgment 11) Known severe congenital or acquired thrombophilia 12) Life expectancy <3 months at the time of screening 13) Other conditions that substantially increase risk of bleeding or thrombosis by the discretion of the investigator 14) Contraindications according to the Investigator’s Brochure of emicizumab 15) Current treatment with emicizumab at time of screening 16) History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the emicizumab injection by the discretion of the investigator 17) 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 local investigator, preclude the patient’s safe participation in and completion of the study 18) Addiction or other diseases that preclude the patient from appropriately assessing the nature and scope as well as possible consequences of the clinical study by the discretion of the investigator 19) Pregnant or breast-feeding women 20) Women of childbearing potential unless women who meet the following criteria: a. Post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum FSH > 40 U/mL) b. Postoperatively (six weeks after bilateral ovariectomy with or without hysterectomy) c. Regular and correct use of a contraceptive method with error rate <1% per year such as implants, depot injections, oral contraceptives or intrauterine devices d. Sexual abstinence e. Vasectomy of the partner 21) Subject is in custody by order of an authority or a court of law 22) Receipt of an investigational drug concurrently or within 5 half-lives before administration of the study drug
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy objective is to evaluate the efficacy of prophylactic emicizumab which will be evaluated by determination of the rate of clinically significant bleeds per patient-week until death or week 12 after starting emicizumab treatment, whatever occurs first. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The secondary study objective to study the safety of emicizumab in patients with AHA will be evaluated on the basis of the incidence and severity of adverse events, thromboembolic events, thrombotic microangiopathy in the 12 weeks after starting emicizumab treatment and mortality in the 24 weeks after starting emicizumab.
Further secondary endpoints include the bleeding-free survival in the 12 weeks after starting emicizumab treatment, mortality and cause of death, days of treatment with and dose of bypassing agents, days in hospital and number of patients archieving partial remission in the 24 weeks after starting emicizumab treatment.
The additional exploratory objective to compare bleeding and adverse events with the historic GTH-AH 01/2010 cohort will be evaluated on basis of 1) the number of clinically significant bleeds per patient-week until death or week 12 after starting treatment, whatever occurs first; 2) the incidence and severity of adverse events, thromboembolic events, thrombotic microangiopathy until week 12 after starting treatment and mortality after 24 weeks, and 3) bleeding-free survival until week 12 after starting treatment.
The additional exploratory objective to compare bleeding and adverse events with a parallel US study will be evaluated on basis of 1) the number of clinically significant bleeds per patient-week until death or week 12 after starting emicizumab treatment, whatever occurs first; 2) the incidence and severity of adverse events, thromboembolic events, thrombotic microangiopathy until week 12 after starting emicizumab treatment and mortality after 24 weeks, and 3) bleeding-free survival until week 12 after starting emicizumab treatment.
PK parameters derived by emicizumab plasma levels will be analyzed and descriptively summarized.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.3 | Therapy | Yes |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 | Yes |
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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As for this study, the primary outcome will be analyzed after the last patient has completed the therapy, thus, the end of the study will be the date when the clean database is available. However, the primary completion event of the study will be the date of last patient last visit (LPLV). |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |