E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Haemophilia A
Haemophilia A with inhibitors
Haemophilia B
Haemophilia B with inhibitors |
|
E.1.1.1 | Medical condition in easily understood language |
Haemophilia A with and without antibodies to clotting factor replacement therapy
Haemophilia B with and without antibodies to clotting factor replacement therapy |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
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 | 10018938 |
E.1.2 | Term | Haemophilia A (Factor VIII) |
E.1.2 | System Organ Class | 100000004850 |
|
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 |
|
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 | 10018939 |
E.1.2 | Term | Haemophilia B (Factor IX) |
E.1.2 | System Organ Class | 100000004850 |
|
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 |
|
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 effect of 1.75 mg/kg concizumab administered once-weekly in maintaining adequate control of bleeding in adult and adolescent patients with haemophilia A or B with or without inhibitors |
|
E.2.2 | Secondary objectives of the trial |
1. To investigate the safety of concizumab once-weekly prophylaxis in adult and adolescent patients with haemophilia A or B with or without inhibitors
2. To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of concizumab once-weekly prophylaxis in adult and adolescent patients with haemophilia A or B with or without inhibitors. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial.
- Male aged 12 years or older at the time of signing informed consent (18 years or older for the PK/PD cohort).
- Diagnosis of congenital severe haemophilia A (FVIII below 1%) or moderate/severe congenital haemophilia B (FIX equal to or below 2%), or congenital haemophilia with inhibitors.
- Patient has been prescribed, or is in need of, treatment with coagulation factor product or bypassing agent in the last 24 weeks prior to screening. |
|
E.4 | Principal exclusion criteria |
- Known or suspected hypersensitivity to any constituents of the trial product.
- Known inherited or acquired coagulation disorder other than congenital haemophilia.
- Ongoing or planned Immune Tolerance Induction treatment. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The number of treated bleeding episodes (spontaneous and traumatic) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From start of treatment (week 0) to the end of the main part (week 24) |
|
E.5.2 | Secondary end point(s) |
1. Number of thromboembolic events
2. Number of hypersensitivity type reactions
3. Number of injection site reactions
4. Patient developed antibodies to concizumab – yes/no
5. Patient developed antibodies to concizumab – yes/no
6. Concizumab plasma concentrations prior to the last prophylaxis dose administration in main part
7. Peak thrombin generation prior to the last prophylaxis dose administration in main part
8. Free TFPI concentration value prior to the last prophylaxis dose administration in main part
9. Concizumab highest plasma concentration (Cmax) during the weekly PK profile
10. Concizumab plasma concentration AUC during the weekly PK profile |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.- 4.: From start of treatment (week 0) to the end of the main part (24 weeks)
5.: From start of treatment (week 0) to the end of trial (week 135)
6.-8..: Week 24
9.-10.:Assessed once between week 7 and week 24 |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.3 |
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 | 24 |
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 |
Canada |
European Union |
India |
Japan |
Korea, Republic of |
Russian Federation |
Serbia |
Switzerland |
Thailand |
Ukraine |
United States |
|
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
|
|
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 | 2 |
E.8.9.1 | In the Member State concerned days | 6 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 6 |