Transthyretin amyloidosis MedDRA version: 9.1 Level: LLT Classification code 10019901
Conditions
Interventions
Pharmaceutical Form: Tablet
INN or Proposed INN: Doxycycline
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical Form: Capsule, hard
INN or Propose
Sponsors
OSPEDALE POLICLINICO S. MATTEO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age = 18 years 2) Male or non-pregnant, non-lactating females 3) Written informed consent 4) Histochemical diagnosis of amyloidosis 5) Molecular definition of the TTR mutation or immunohistochemical staining of amyloid fibrils with anti TTR antibody 6) ECOG performance status (PS) 0, 1, 2 7) NYHA class =III 8) Systolic blood pressure =100 mmHg (standing) 9) Must have symptomatic organ involvement with amyloid to justify therapy; must have evidence of neuropathy and/or cardiomyopathy progression after liver transplantation performed since at least one year. 10) Willingness to return to the treating center for follow up. 11) Contraception for women of childbearing potential. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Liver transplantation in the previous 12 months or liver transplantation anticipated in less than 6 months; 2) ALT e/o AST = 2 x UNL 3) ALP = 2 x UNL 4) Creatinine clearance < 30 ml/min; 5) Any other lab values that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study; 6) Echocardiographic ejection fraction < 50%; 7) Other neuropathies, due to vitamin B12 deficiency, alcoholism, hypothyroidism, uremia, diabetes mellitus, vasculitides; 8) History of poor compliance; 9) History of hypersensitivity to any of the ingredients of the study therapies; 10) Use of any investigational drug, device (or biologic) within 4 weeks prior to study entry or during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of doxycycline + TUDCA on disease progression in ATTR subjects;Secondary Objective: 1. To evaluate the safety and tolerability of doxy + TUDCA in ATTR subjects over 12 months. 2. To evaluate general and health related quality of life (QoL) in ATTR subjects. 3. To evaluate symptoms and signs of peripheral sensorimotor neuropathy when present. 4. To evaluate signs of cardiomyopathy when present. 5. To evaluate disease evolution (maintenance of response, occurrence of disease progression) over 18 months. 6. To assess doxycycline pharmacokinetics (PK).;Primary end point(s): Response rate to doxycycline + TUDCA treatment at 12 months | — |
Countries
Italy
Outcome results
None listed