E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
- Patients with severe congenital hemophilia A - Patients with mild-moderate hemophilia A - Heterozygous carriers of hemophilia A - Patients with VWD Type 1, e.g. “Vicenza” type - Acquired Von Willebrand Syndrome (aVWS) without specific inhibitor - Patients with VWD Type 2b - Patients with VWD Type 3 on substitution VWF therapy
|
|
E.1.1.1 | Medical condition in easily understood language |
Patients with hereditary bleeding disorders |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
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 this study is to obtain clinical proof of mechanism for BT200 in one or more hereditary bleeding disorders. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objective of this study is to assess the PK/PD relationship for BT200 in patients with hereditary bleeding disorders. In a pop-PK-sub-study the half-life of the substituted FVIII product with and without BT-200 will be determined.
The exploratory objectives of this study are to evaluate the safety, and tolerability of BT200 in patients with hereditary bleeding disorders. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for this study, subjects must meet all of the following inclusion criteria: 1. Hereditary bleeding disorder: - Congenital hemophilia A without inhibitors with a prophylactic treatment regime - Heterozygous carriers of hemophilia A with subnormal FVIII levels - VWD Type 1, “Vicenza” type Von Willebrand Syndrome (VWS) without specific inhibitors - VWD Type 2b - VWD Type 3 under substitution VWF therapy - Acquired Von Willebrand Syndrome (aVWS) without specific inhibitors
2. Male or female, age ≥ 18 years old at screening 3. If female, must be post-menopausal, surgically sterilized or willing and able to use highly effective methods of birth control throughout the study and for 30 days after the end-of trial (EOT) visit. (NB: Women are the target population for a hemostatic drug because VWD and carrier status of hemophilia causes menorrhagia often severe enough to lead to hysterectomy.) 4. Able to comprehend and to give informed consent 5. Able to cooperate with the Investigator, to comply with the requirements of the study, and to complete the full sequence of |
|
E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria will be excluded from the study: 1. Clinically significant medical history or ongoing chronic illness that would jeopardize the safety of the subject or compromise the quality of the data derived from his/her participation in this study 2. Females who are pregnant (positive pregnancy test at screening or during study phase), lactating, or, if having reproductive potential, are considered potentially unreliable with respect to contraceptive practice 3. History of infusion hypersensitivity reactions, significant drug allergy, or anaphylactic reactions 4. Substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the Investigator for the subject to be able to comply fully with study procedures 5. Use of medication during 2 weeks before the start of the study, which in the judgment of the Investigator may adversely affect the subject’s welfare or the integrity of the study’s results 6. Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days or 5 elimination half-lives (whichever is longer) prior to treatment start
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint varies according to hematologic diagnosis. - Hemophilia A: increase in FVIII activity - VWD Type 1 & VWS: increase in FVIII activity - VWD Type 2b: increase in platelet count and/or FVIII activity - VWD Type 3 under substitution VWF therapy: increase in trough VWF and FVIII activity levels - aVWS: increase in FVIII activity
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Continuous evaluation for the duration of the subject's participation in the trial |
|
E.5.2 | Secondary end point(s) |
Pharmacokinetics: • Measured concentration of BT200 (and derived PK parameters) • Half-life of the substituted Factor VIII product used with and without BT200 application (pop-PK-sub-study) Pharmacodynamics: • Platelet Function Analyzer (PFA-100®) • Multiplate electrode platelet aggregometer (ristocetin induced) • VWF:ristocetin co-factor assay (VWF:RiCo) • VWF collagen binding assay (VWF:CBA) • Enzyme-linked immunosorbent assay (ELISA) for unbound VWF A1 domain (REAADS®) • VWF propeptide (VWF:pp) • VWF Multimers (non obligatory) • D-dimer and prothrombin fragment (F1.2) • Endogenous thrombin potential (ETP) • Rotational thrombelastometry (ROTEM) • Clot strength assay
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Continuous evaluation for the duration of the subject's participation in the trial |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
|
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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
|
|
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 | |
E.8.9.1 | In the Member State concerned days | |