Non-V30M Transthyretin Amyloidosis
Conditions
Interventions
2-(3,5-dichloro-phenyl)-benzoxazole-6-carboxylat
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Sponsors
FoldRx Pharmaceuticals Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient has amyloid documented by biopsy (in accordance with institutional site standard of care); - Patient has documentation of one of the following targeted TTR mutations: Ser77Tyr, Thr60Ala, Tyr114Cys, Leu58His, Glu89Gln, Ser77Phe, Thr49Ala, Ile107Val, Val30Ala, Gly47Ala, Gly47Glu, Leu55Arg, Lys70Asn, Ile84Thr, Ile107Met. Patients with mutations other than those listed may be enrolled only after approval by the Sponsor; - Patient has peripheral and/or autonomic neuropathy and/or cardiomyopathy with a Karnofsky Performance Status = 50; - Patient is aged =18 to 75 years, inclusive; - If female, patient is post-menopausal, surgically sterilized, or willing to use two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide) throughout the study and for 3 months from the end of the study. (A condom alone is not considered an acceptable method of birth control.) If male with a female partner of childbearing potential, willing to use two acceptable methods of birth control for the duration of the study. For both females and males, acceptable birth control must be used for at least 3 months after the last dose of study medication; - Patient is, in the opinion of the investigator, willing and able to comply with the study medication regimen and all other study requirements 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: - Chronic use of non-protocol approved non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3-4 times/month. The following NSAID are allowed: acetylsalicylic acid, etodolac, ibuprofen, indomethicin, ketoprofen, nabumetone, naproxen, nimesulide, piroxicam, and sulindac; - Patient has primary or secondary amyloidosis; - Patient has TTR-associated amyloidosis with V30M mutation; - If female, patient is pregnant or breast feeding; - Patient has received prior liver transplantation; - Patient is expected to undergo liver transplantation within 12 months after enrollment; - Patient with positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV); - Patient has renal insufficiency (creatinine clearance 2 times upper limit of normal (ULN) that in the medical judgment of the investigator are due to reduced liver function or active liver disease; - Patient has a New York Heart Association (NYHA) Functional Classification = III; - Patient has other causes of sensorimotor neuropathy (B12 deficiency, Diabetes Mellitus, HIV treated with retroviral medications, thyroid disorders, alcohol abuse, and chronic inflammatory diseases); - Patient has prior non-amyloid cardiac disease such as: myocardial infarction due to obstructive coronary artery disease, active non-amyloid cardiomyopathy (e.g., symptomatic left ventricular dysfunction from any cause other than amyloid, patients with a primary diagnosis of symptomatic valvular heart disease); - Patient has a co-morbidity anticipated to limit survival to less than 12 months; - Patient has received an investigational drug/device and/or participated in another clinical investigational study within 60 days before Baseline (Day 0).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - to determine TTR stabilization at steady-state, as measured by a validated immunoturbidimetric assay, in patients with non-V30M TTR amyloidosis.;Secondary Objective: - to evaluate the safety and tolerability of Fx-1006A in patients with non-V30M TTR amyloidosis; - to determine plasma concentrations at selected steady-state time points; - to evaluate clinical outcomes in patients with non-V30M TTR amyloidosis;Primary end point(s): Primary endpoint: TTR stabilization at Week 6 compared with Baseline, as measured by a validated immunoturbidimetric assay; Secondary endpoint: TTR stabilization at Months 6 and 12 compared with Baseline, as measured by a validated immunoturbidimetric assay. Safety endpoints: - Incidence of patients experiencing treatment-emergent adverse events - Incidence of patients experiencing treatment-emergent = Grade 3 adverse events - Incidence of patients with treatment-emergent echocardiography findings considered by the Investigator to be clinically significant - Incidence of patients with treatment-emergent electrocardiogram (ECG) findings considered by the Investigator to be clinically significant - Incidence of patients with treatment-emergent Holter monitoring findings considered by the Investigator to be clinically significant - Incidence of patients discontinuing from the study because of clinical or laboratory adverse events Exploratory endpoints: - Change from Baseline in the NIS and NIS-LL scores at Months 6 and 12 - Response to treatment at Months 6 and 12, defined as: a responder is a patient with a change from Baseline in the NIS-LL of < 2 (improvement if score decreases from Baseline; stabilization if change from Baseline is 0 to < 2); a non-responder is a patient with a change from Baseline in the NIS-LL = 2 - Change from Baseline in the TQOL and five domains of the Norfolk QOL-DN at Months 6 and 12 - Change from Baseline in nerve conduction studies (NCS) at Months 6 and 12 - Change from Baseline in heart rat | — |
Countries
France, Germany, Italy
Outcome results
None listed