E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
functional single ventricle physiology
functional single left ventricle
functional single right ventricle
functional single biventricle |
|
E.1.1.1 | Medical condition in easily understood language |
congenital heart defect that requires surgical intervention |
|
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 | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040729 |
E.1.2 | Term | Single ventricle |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
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 |
Evaluation of the safety of the TEVG as defined by 'number of patients with graft related post-operative complications' requiring surgery or leading to death within the first 6 months after TEVG implantation |
|
E.2.2 | Secondary objectives of the trial |
Evaluation of the efficacy of the implated TEVG, analysing the incidence of:
- Loss of functionality of the TEVG requiring surgery
- Medical condition related to TEVG requiring surgery withing 6, 12, 24 and 36 months after TEVG implantation
Evaluation of the long-term safety of the implanted TEVG, as defined by 'number of patients with graft related post-operative complications' within 12, 24 and 36 months after TEVG implantation
Evaluation of the biological growth in diameter of the TEVG within 12, 24 and 36 months after TEVG implantation |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Functional single ventricle physiology (functional single left ventricle,
functional single right ventricle, functional single biventricle)
- Male or female
- Age: 2 - 6 years
- Parental / legal guardian’s consent on behalf of the minor subject |
|
E.4 | Principal exclusion criteria |
- Pulmonary artery pressure (PAP) > 15 mm Hg as excluded by angiography/cardiac catheter
- Pulmonary vascular resistance (PVR) >3 Wood units as excluded by angiography/cardiac catheter
- Moderate or severe atrioventricular (AV) valve regurgitation requiring correction, as determined by echocardiography and / or angiography
- Moderate or severe outflow valve regurgitation requiring correction as
determined by echocardiography and / or angiography
- Outflow tract (aortic arch and isthmus) obstruction as excluded by
a) a residual outflow gradient of ≥ 20mm Hg or
b) requirement of corrective surgery
as determined by angiography/cardiac catheter
- All arrhythmia other than normal sinus rhythm as determined by ECG
and / or at the investigator’s discretion
- Renal dysfunction as excluded by serum creatinin > ULN and / or urea
>ULN and / or at the investigator’s discretion
- Hepatic dysfunction as excluded by ALT >ULN, AST > ULN, GGT >
ULN and / or at the investigator’s discretion
- Coagulation disorders as defined by INR outside its normal value, PTT
>ULN and Fibrinogen <LLN and / or at the investigator’s discretion
- Transcutaneous O2 saturation < 65% or at the investigator’s discretion
- Immunodeficiency (ies) / Immune-syndromes
- Trisomia 21
- Asplenia as excluded by abdominal ultrasound
- Heterotaxia as excluded by abdominal ultrasound
- HIV-infection
- Syphillis (Treponema pallidum)
- Hepatitis-B and /or –C virus infection
- Unwillingness of Parental / legal guardian’s to give consent
- Contraindications on ethical grounds
- Treatment with other investigational products
- Known or suspected non-compliance, drug or alcohol abuse of the parents / legal guardian
- Inability of the parents / legal guardians to follow the procedures of the study, e.g. due to language problems
- Participation of the patient in another study within 30 days preceding
and during the present study
- Previous enrollment of the patient into the current study
- Enrollment of the investigator’s family members, employees and other
dependent persons |
|
E.5 End points |
E.5.1 | Primary end point(s) |
This primary study endpoint is the safety of the TEVG after 6 months of postimplantation.
This endpoint will be evaluated by the number of patients with graft related postoperative
complications requiring surgery or leading to death within the first 6 months of post-implantation. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 month after TEVG implantation |
|
E.5.2 | Secondary end point(s) |
Safety:
Secondary study endpoints will address the long-term safety of the implanted TEVG,
as defined by ‘number of patients with graft related post-operative complications’ within the first
12, 24, 36 months after TEVG implantation by assessing all SAEs / graft related SAEs and cardiovascular related other relevant AEs.
Evaluation of the efficacy of the implanted TEVG, analysing the incidence of Loss of functionality of the TEVG requiring surgery
Medical condition related to TEVG requiring surgery within 6, 12, 24 and 36 months after TEVG implantation.
Evaluation of biological growth:
Evaluation of the biological growth of the TEVG will be determined by
echocardiographic measurements of the diameter of the TEVG until 36 months after
surgery. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
6, 12, 24 and 36 months after TEVG implantation |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Evaluation of biological growth of implant |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | 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 | 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
| 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 | 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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |