E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Familial transthyretin amyloidosis |
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E.1.1.1 | Medical condition in easily understood language |
Familial transthyretin amyloidosis |
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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 | 13.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019893 |
E.1.2 | Term | Hereditary neuropathic amyloidosis, Swedish type |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 follow the development of neurological, nutritional and cardiac manifestations of transthyretin amyloidosis in patients treated by Diflunisal 250 mg twice daily. |
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E.2.2 | Secondary objectives of the trial |
collect and report adverse reactions |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Biopsy and genetically proven systemic transthyretin amyloidosis caused by a TTR gene mutation. The amyloid shall be proven to be of tranthyrein type, and the fibril composition settled.
2. Age ≥ 18 years.
3. Negative pregnancy test and contraception for sexually active women of child bearing potential.
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E.4 | Principal exclusion criteria |
1. Concomitant use of non-study NSAIDs
2. Heart failure with symptoms at daily activities (NYHA class ≥III)
3. Renal insufficiency (kreatinine clearence < 30 ml calculated from the Cocroft-Gault formula)
4. Active non-haemorrhoidal bleeding within the last 18 month.
5. Non-treated peptic ulcer disease.
6. Anticoagulation therapy, low dose ASA permitted.
7. Non-steroidal or aspirin allergy/hypersensitivity
8. Thrombocytopenia (< 100,000 platelets/mm3)
9. Inability or unwillingness of subject to give written informed consent
10. By the investigator regarded as unable to follow the study guidelines and scheduled controls.
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E.5 End points |
E.5.1 | Primary end point(s) |
Changes in the Kumamoto scale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 12 and 18 month treatment. Dependent of when results from the ongoing international study can be presented a 24 month evaluation can be performed in this study. |
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E.5.2 | Secondary end point(s) |
1. changes in nutritional status measured by the modified body mass index (mBMI)
2. neurological impairment measured by the PND-score
3. cardiac impairment measured by echocardiographic measurement of septal thickness and by proBNP in blood samples.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 12 and 18 month of treatment. Dependent of when results from the ongoing international study can be presented a 24 month evaluation can be performed in this study. |
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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 | No |
E.6.3 | Therapy | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
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
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This study will continue until the results from the ongoing international muliticenter study with diflunisal is presented. Approximately until summer 2013. |
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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 | 2 |
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 | 2 |
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 |