E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | PT |
E.1.2 | Classification code | 10002022 |
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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 |
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; Laboratory values obtained </= 30 days prior to registration (Echocardiographic ejection fraction >/=50%; Total bilirubin </= 2.0 mg/dl, or direct bilirubin </=1.0 mg/dl; Alkaline phosphatase </=4 x UNL; ALT or AST </= 2 x UNL; Creatinine clearance >/= 40 ml/min or creatinine </=2 mg/dL); histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens; At least one of the following: Molecular definition of the TTR mutation, .Immunohistochemical stain with anti TTR antisera of amyloid fibrils. ECOG performance status (PS) 0, 1, 2.; Systolic blood pressure >/=100 mmHg (standing); NYHA class </=III; Must have symptomatic organ involvement with amyloid to justify therapy; must have neuropathy. Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent.Willingness to return to the treating center for follow up.Willingness to provide all biologic specimens as required by the protocol.Patients may be either previously untreated or previously treated.Contraception for women of childbearing potential. |
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E.4 | Principal exclusion criteria |
Prior liver transplantation or liver transplantation anticipated in < 1 year. Any of the following: Uncontrolled infection; Any known active inflammatory process; Significant acute gastrointestinal symptoms; Active peptic ulceration and/or esophageal reflux disease; history of drug hypersensitivity; Smokers; psychiatric illness; Social situations that would limit compliance with study requirements (e.g.: history of drug abuse); Any of the following: Pregnant or Nursing women; Initiation of or any changes in other medications/supportive therapy (excluding vitamins) within 3 months prior to enrollment; other neuropathies. |
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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. |
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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 | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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
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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 | 2 |
E.8.9.1 | In the Member State concerned days | |
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 | 2 |