E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
Hereditary bleeding disorder caused by a lack of blood clotting factor |
|
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 | 10018939 |
E.1.2 | Term | Haemophilia B (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 |
Safety
-To assess the long-term safety following systemic administration of FLT180a in patients with haemophilia B.
-To investigate the durability of endogenous Factor IX (FIX) activity following systemic administration of FLT180a. |
|
E.2.2 | Secondary objectives of the trial |
To investigate the long-term effectiveness of FLT180a on annualized bleeding rate and exogenous FIX consumption.
To investigate the effectiveness of FLT180a related to surgical or dental procedures.
To describe the immune responses to the human FIX (hFIX) transgene product following systematic administration of FLT180a.
To assess viral shedding in various body fluids after systematic administration of FLT180a. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients who have previously received FLT180a within a clinical study.
2. Able to give full informed consent and able to comply with all requirements of the study including long-term follow-up for the timeframe the study requires.
3. Willing to practice barrier contraception until at least 3 consecutive semen samples after vector administration are negative for vector sequence*.
*only applicable if vector genome shedding in semen sample persists at end of study in the preceding clinical study where FLT180a is administered. |
|
E.4 | Principal exclusion criteria |
None, if both inclusion criteria are met |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary Safety Endpoint
• Safety as assessed by the reporting of adverse events (AEs)/adverse reactions (ARs) according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 or later.
Primary Efficacy Endpoint
• The durability of response will be estimated from the rate of decline of the FIX activity observed. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary Safety Endpoint at Day 1, at Month 3,6,12,18, than Annually until EoS
Primary Efficacy Endpoint at Day 1, at Month 3,6,12,18, than Annually at Year 2,3,4,5
|
|
E.5.2 | Secondary end point(s) |
Endogenous hFIX Production
Haemostatic Effectiveness
Immune Response
Safety
Shedding |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endogenous hFIX Production: at Day 1, at Month 3,6,12,18, than Annually at Year 2,3,4,5
Haemostatic Effectiveness: at Day 1, at Month 3,6,12,18, than Annually at Year 2,3,4,5
Immune Response: at Day 1, at Month 3,6,12,18, than Annually at Year 2,3,4,5 |
|
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 | 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) | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Long-Term Safety and Efficacy Follow-up. No administration of treatment included. |
|
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 |
Germany |
Ireland |
Italy |
South Africa |
Sweden |
United Kingdom |
United States |
|
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 | 14 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 14 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |