Active clinical trials for "Amyloid Neuropathies"

The purpose of this study is to evaluate the safety and efficacy of patisiran (ALN-TTR02) in patients with transthyretin (TTR) mediated amyloidosis. An open-label, single-arm, long-term follow-up extension study NCT02510261 (ALN-TTR02-006) was initiated to provide participants who completed this study with continued patisiran-LNP (lipid nanoparticle) treatment.

This study is designed to determine the long-term safety and tolerability of Fx-1006A as well as the effects of Fx-1006A on clinical outcomes in patients with ATTR-PN. All patients who enroll in this extension study will receive once-daily oral 20 mg Fx-1006A for 12 months; therefore, patients randomized to placebo in Study Fx-005 will cross over to active drug (Fx-1006A 20 mg) during this study. However, patients and their families as well as clinical Investigators and their clinical site staff will remain blinded to the original Fx-005 treatment assignment. It is intended that there will be no interruption in study medication administration between the two studies. The majority of safety and clinical outcomes assessments will be identical to those evaluated in Study Fx-005. Additional assessments for this open-label extension study include 24-hour Holter monitoring and skin biopsy for IENF; patients will be required to provide written informed consent to participate in this open-label extension study prior to having these additional procedures performed. The values obtained from procedures and evaluations conducted during the Month 18 visit of Study Fx-005 will be used as the Baseline values for this open-label extension study. The Baseline assessments of IENF and Holter monitoring may be conducted at either day of the Month 18 visit days of Study Fx-005, but prior to the first Fx-1006A dose in this open-label extension study. Clinic Visits will be conducted at Week 6 (± 2 days), and Month 3 (± 1 week), Month 6 (± 2 weeks), and Month 12 (± 2 weeks). Monthly telephone contacts (± 1 week of the scheduled date) will be made during months in which no investigative site visits are scheduled (Months 2, 4, 5, 7, 8, 9, 10, and 11) for assessment of adverse events and concomitant medications. Neurological evaluation by NIS-LL will be performed at Months 6 and 12. The NIS-LL will be assessed by utilizing the average of two successive NIS-LL clinical assessment scores obtained at least 24 hours apart within a one week period for each study visit. A dedicated neurologist will be required to perform NIS-LL scoring across all time-points for each individual patient enrolled in the study. Quality of life utilizing the Norfolk QOL-DN will be assessed at Months 6 and 12 (based on the total score as well as the five individual domains of the questionnaire). QST (utilizing CASE IV), NCS, HRDB, mBMI, and echocardiography will be conducted at Months 6 and 12. Holter monitoring will be conducted at Baseline and Months 6 and 12. Biopsies for IENF will be obtained at Baseline only. Assessments of troponin I and NT-pro-BNP levels will be made at each study visit. Blood samples for pharmacokinetic assessments (Fx-1006A concentrations as well as calculated steady-state parameters) and pharmacodynamic assessments (TTR stabilization) will be collected at Week 6 and Months 6 and 12. Safety and tolerability will be assessed throughout the study. Vital signs, 12-lead ECG, blood and urine samples for clinical laboratory tests (serum chemistry, hematology, coagulation panel, urinalysis, and urine pregnancy testing), adverse events, and concomitant medications will be assessed at each study visit. Eye examinations (including fundal photography) will be conducted at Months 6 and 12. Abbreviated physical examinations will be conducted at Week 6, and Months 3 and 6, and a complete physical examination will be conducted at Month 12. All patients will be contacted by telephone 30 days (± 1 week) after the last dose of study medication for assessment of adverse events and concomitant medications. Patients who complete the Month 12 visit of this open-label study may be allowed to continue receiving Fx-1006A under a compassionate use program. Patients who discontinue from the study at any time after enrollment (i.e., early termination) will have final safety assessments performed at the time of discontinuation. Any patient discontinuing after the Month 6 visit will have all safety and clinical outcomes assessments scheduled for the Month 12 visit performed.

This study will examine whether Fx-1006A is effective in halting the progression of Familial Amyloid Polyneuropathy (FAP). Deposition of TTR amyloid is associated with a variety of human diseases. Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP. The prevention of the formation of amyloid by stabilization of the TTR native state should constitute an effective therapy for amyloid diseases. Therapeutic intervention with a TTR stabilizer drug, such as Fx-1006A, is hypothesized to stop progression of the disease in FAP patients. FAP is a uniformly fatal disease and Fx-1006A is intended to halt the relentless neurological deterioration FAP patients experience. This Phase 2/3 study will enroll early to mid-stage FAP patients in order to interrupt and stabilize the disease at a point in time where progression of motor and autonomic dysfunction can be maximally effected. Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months.

To evaluate the efficacy and safety of eplontersen after administration for 65 weeks to patients with hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN), as compared to the NEURO-TTR trial (NCT01737398). For more information, please visit http://www.neuro-ttransform.com/.

This is a single-arm, open-label, multicenter study designed to determine the effect of tafamidis meglumine on TTR stabilization as well as tafamidis meglumine safety, tolerability and efficacy in ATTR-PN patients in China. Approximately 10-15 participants are planned to be enrolled. All enrolled participants will receive oral tafamidis meglumine 20 mg soft capsules once daily for 72 weeks (18 months).

The purpose of this study is to evaluate the efficacy and safety of inotersen given for 65 weeks in participants with Familial Amyloid Polyneuropathy (FAP).

Tafamidis has been developed as an oral specific stabilizer of transthyretin tetramer.

The purpose of this study is to determine if diflunisal can prevent progressive lower leg nerve damage in patients with familial amyloidosis polyneuropathy. Funding Source - FDA Office of Orphan Products Development (OOPD); National Institute of Neurological Disorders and Stroke (NINDS)

Familial amyloid neuropathies (FAP) are hereditary disease due to a mutation of the tranthyretin gene (TTR). These neuropathies are severe and life frightening. Asymptomatic carrier of TTR mutation are now detected in large TTR-FAP family. However, it is very hard to detect the moment where a TTR mutation carrier become symptomatic: too early diagnosis exposes the patients to side effect of the treatment and too late diagnosis exposes the patient to disease progression and clinical sequels. Neurological monitoring comprises clinical examination, electrophysiology and imaging. Sensitivity and specificity of these tools are not sufficient and we have to develop new biomarkers sensitive enough to detect modifications under treatment and the moment where a TTR mutation carrier become symptomatic Magnetic resonance imaging (MRI) can well evaluate neuromuscular diseases. Electrophysiological examination is also a good tool to evaluate NAF. MUNIX is a technique that permits to estimate the number of motor unit in one muscl. MUNIX is related to the disability in chronic inflammatory neuropathies and could be more sensitive than clinical scales and other electrophysiological data to detect modification of the disease in TTR-FAP. The objective of this exploratory study is to test the applicability of MUNIX and MRI as early measures for detecting the transition from asymptomatic to symptomatic TTR-FAP. In symptomatic TTR-FAP we will determine if MUNIX and MRI data are related to clinical deficiency and disability of the patients. This is a transversal exploratory study. If we manage to demonstrate that MRI and MUNIX can segregate symptomatic versus asymptomatic TTR mutation gene carriers, we will propose a longitudinal study with a follow up of more asymptomatic gene carriers.

Phase 3 efficacy and safety of acoramidis in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)