E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transthyretin amyloidosis ATTR |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10034606 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Primary objective is to establish the clinical efficacy, in terms of response rate, of doxycycline in ATTR |
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E.2.2 | Secondary objectives of the trial |
The following variables will be assessed and evaluated in all patients safety profile time to progression of amyloidosis-associated clinical symptoms and/or organ dysfunction duration of response |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
age / 18 years, histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens, NYHA class / III, contraception for women of potential childbearing, ... |
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E.4 | Principal exclusion criteria |
prior liver transplantation or liver transplantation anticipated in 1 year, uncontrolled infection, any known active inflammatory process, significant acute gastrointestinal symptoms, active peptic ulceration, ... |
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E.5 End points |
E.5.1 | Primary end point(s) |
Response is the primary endpoint and will be evaluated according to response criteria listed below. Evaluation of treatment efficacy will be performed after 3 and 6 cycles. Improvement of one or more affected organ s as defined by Neuropathy clinical improvement according to the Kumamoto Neurologic Scale9 and/or to EMG studies. Patients will need at least 1 point improvement on their neuropathy disability score. Heart / 2 mm reduction in interventricular septal IVS thickness by echocardiogram or improvement of ejection fraction by / 20 echocardiogram must be performed at the same institution or 50 reduction of abnormal NT-proBNP concentration or return into reference interval. GI tract reduction of diarrhea to less than 50 of previous movements/day. Malabsorption will be evaluated by serial measurement of transthyretin concentration. It has been reported that increase of TTR 4 mg/dL/week reflect improved nutritional status. Only 1 parameter is required to satisfy the response criteria. |
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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 | 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 | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | 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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |