Safety and Efficacy Study of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis

A Phase II Multicenter Pilot Study of the Safety and Efficacy of Doxycycline/UrsoDeoxyCholicAcid on Disease Progression in ATTR Amyloidosis

The primary objective for this study is to evaluate the efficacy of doxycycline + ursodeoxycholic acid (UDCA) on disease progression in Transthyretin Amyloidosis (ATTR) subjects with cardiomyopathy with or without neuropathy.

Inclusion Criteria:

• Cardiomyopathy with septal thickness > 15 mm and/or S-NT-ProBNP > 300 ng/
• Age >50 years
• Male and females after menopause. Menopause is defined as 6 to 12 months of amenorrhea in a woman over 45 years of age.
• Written informed consent to be obtained prior to any study procedure
• 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.
• Molecular definition of the TTR mutation or immunohistochemical staining of amyloid fibrils with anti TTR antibody
• New York Heart Association (NYHA) class <III
• Systolic blood pressure >100 mmHg (standing)
• Must have symptomatic organ involvement with amyloid to justify therapy

Exclusion Criteria:

• Liver transplantation in the previous 6 months or liver transplantation anticipated in less than 6 months;
• ALT and/or AST > 2 x upper normal limit (UNL);
• Creatinine clearance < 30 ml/min (Cockcroft -Gault Formula)
• 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;
• History of hypersensitivity to any of the ingredients of the study therapies;
• Use of any investigational drug, device (or biologic) within 4 weeks prior to study entry or during the study.