E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Hemophilia A and B are genetically inherited bleeding disorders caused by the deficiency of Factor VIII (FVIII) or Factor IX (FIX), respectively. |
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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 | 10053751 |
E.1.2 | Term | Hemophilia A with anti factor VIII |
E.1.2 | System Organ Class | 100000004850 |
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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 | 10053753 |
E.1.2 | Term | Hemophilia A without inhibitors |
E.1.2 | System Organ Class | 100000004850 |
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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 | 10053752 |
E.1.2 | Term | Hemophilia B with anti factor IX |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053754 |
E.1.2 | Term | Hemophilia B 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 assess the safety and tolerability of multiple subcutaneous doses of BAY 1093884 in subjects with hemophilia A or B with or without inhibitors. |
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E.2.2 | Secondary objectives of the trial |
There are no secondary objectives in the trial.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The PK sub-study is fully integrated within the study protocol with no separate title. Short description: Blood samples in at least 2 subjects per dose cohort will be drawn for PK analyses of BAY 1093884. These samples will be collected at the following time points: pre-dose, 4h, 24h, 96h, 168h after administration of BAY 1093884, both at week 0 and week 11. It is an optional sub-study for subjects, and separate consent will be requested from the subjects.
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E.3 | Principal inclusion criteria |
1.Male severe hemophilic patients with undetectable FVIII activity <1% or FIX activity <2%, with or without inhibitors (any titer) are eligible. Note: Subjects with a past history of inhibitors (any inhibitor titer) are eligible. 2. Age ≥18 years. 3. Documentation of ≥4 bleeding episodes (any type or location of bleeds, treated or not) within the 6 months prior to screening. 4. For subjects on prophylaxis: Willingness to interrupt ongoing prophylaxis. 5. For subjects on immune tolerance induction (ITI): Willingness to interrupt ongoing ITI. 6. Signed informed consent. |
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E.4 | Principal exclusion criteria |
1. History of any other coagulation disorder (particularly disseminated intravascular coagulopathy or combined FVIII/FV deficiency) or platelet disorder. 2. History of diseases related to venous thromboembolic events (e.g., pulmonary embolism, deep vein thrombosis, thrombophlebitis) or thrombotic microangiopathy. 3. Risk factors for venous or arterial diseases (e.g., uncontrolled hypertension, uncontrolled diabetes). 4. History of cardiac, coronary and/or arterial peripheral atherosclerotic disease, particularly myocardial infarction, cerebrovascular accident, stroke, transient ischemic attack, congestive heart failure, angina pectoris or treatment for angina pectoris. 5. Platelet count <100,000/µL. 6. Human immunodeficiency virus (HIV) infection with a cluster of differentiation 4 (CD4+) lymphocyte count of <200/mm3. 7. Any planned major surgical intervention. 8. Subjects with known or suspected hypersensitivity to trial product(s) or related products. 9. Subjects with known autoimmune disease or on treatment with immune-modulatory drugs. 10. Subjects with advanced liver disease (Child-Pugh Grade B and C) or with signs of liver function impairment (e.g., alanine aminotransferase [ALT] and aspartate aminotransferase [AST] levels >3 × the upper limit of the normal range and/or total bilirubin >2 × the upper limit of the normal range). 11. Subjects with serum creatinine >2.0 times the upper limit of the normal range. 12. Treatment with an investigational drug within 3 months prior to enrolment. 13. Subjects not willing to stop prophylaxis or ITI. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is safety as defined by the frequency of drug-related AEs, SAEs, AESIs and clinically relevant abnormal laboratory values. Another safety endpoint will be the frequency of binding and neutralizing antibodies against BAY 1093884.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout the conduct of the study. |
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E.5.2 | Secondary end point(s) |
There is no secondary endpoint |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
Sequential enrollment into different dose cohorts. |
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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.8.3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Austria |
Bulgaria |
France |
Hungary |
Italy |
Japan |
Korea, Republic of |
New Zealand |
Taiwan |
United Kingdom |
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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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The date when the last subject in Cohort 3 has completed 24 weeks of treatment will be the primary completion date (ie. Part A and first set of 12 weeks in Part B). After the primary completion date, all subjects will either remain on the current dose for long-term safety evaluation or will escalate to the next higher opened dose, if dose escalation criteria are fulfilled. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |