Transthyretin amyloidosis MedDRA version: 14.1 Level: LLT Classification code 10019893 Term: Hereditary neuropathic amyloidosis, Swedish type System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Trade Name: Ursofalk
Product Name: Ursofalk
Pharmaceutical Form: Capsule, hard
CAS Number: 128-13-2
Other descriptive name: URSODESOXYCHOLIC ACID
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Umeå University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Cardiomyopahty with septal thickness >/= 15 mm and/or S-NT-ProBNP >/=300 ng/L 2) Age >/=50 years 3) Male and females after menopause 4) Written informed consent to be obtained prior to any study procedure 5) Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens, and typing of amyloid deposits as TTR and identification of amyloid fibril type. 6) Molecular definition of the TTR mutation or immunohistochemical staining of amyloid fibrils with anti TTR antibody 7) NYHA class /=100 mmHg (standing) 9) Must have symptomatic organ involvement with amyloid to justify therapy 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: Liver transplantation in the previous 6 months or liver transplantation anticipated in less than 6 months; 2) ALT and/or AST >/= 2 x UNL; 3) Creatinine clearance < 30 ml/min (Cocroft-Gault Formula) 4) Any other lab values, illness or condition that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study; 5) History of hypersensitivity to any of the ingredients of the study therapies; 6) 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 + UDCA on disease progression in ATTR subjects with cardiomyopathy with or without neuropathy.;Secondary Objective: 1. To evaluate the safety and tolerability of doxycyclin + UDCA in ATTR subjects over 12 months. 2. To evaluate symptoms and signs of peripheral sensorimotor neuropathy when present (Kumamoto Scale). 3. To evaluate disease evolution (maintenance of response, occurrence of disease progression) over 18 months. 4. To evaluate the outcome of the treatment with regard to type of amyloid fibrills ;Primary end point(s): Response rate to doxycycline + UDCA treatment at month 12. A responder is an ATTR subject with: - a reduction of, or an increase in serum NT-proBNP concentration of less than 30% of pre-treatment level will be regarded as consistent with treatment efficacy. ;Timepoint(s) of evaluation of this end point: After 12 month of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -mBMI-reduction of less than 10% after 12 months of treatment - increase of septum thickness = 2 mm during 12 months of treatment. - to assess the change from baseline in the neurologic Kumamoto Scale at months 6, 12 and 18; - to assess the tolerability and safety of the treatment, i.e. monitoring and recording all adverse events (AEs) and serious adverse events (SAEs), and the regularly scheduled monitoring of hematology, blood chemistry, physical examinations, and blood pressure over 12 months and 18 months. ;Timepoint(s) of evaluation of this end point: At 6, 12 and 18 month | — |
Countries
Sweden
Outcome results
None listed