Safety and Efficacy Study of Fx-1006A in Patients With Familial Amyloidosis

Safety and Efficacy of Orally Administered Fx-1006A in Patients With Familial Amyloid Polyneuropathy (FAP): A Randomized, Double-blind, Placebo-controlled Study

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.

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.

Inclusion Criteria:

1. Amyloid documented by biopsy.
2. Documented V30M TTR mutation.
3. Peripheral and/or autonomic neuropathy with a Karnofsky Performance Status ≥50.
4. Patient is 18-75 years old.
5. If female, patient is post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control. If male with a female partner of childbearing potential, willing to use an acceptable method of birth control for the duration of the study. For both females and males, birth control must be used for at least 3 months after the last dose of study medication.
6. Patient is, in the opinion of the investigator, willing and able to comply with the study medication regimen and all other study requirements.

Exclusion Criteria:

1. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs).
2. Primary amyloidosis.
3. If female, patient is pregnant or breast feeding.
4. Prior liver transplantation.
5. No recordable sensory threshold for vibration perception in both feet, as measured by CASE IV.
6. Positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
7. Renal insufficiency or liver function test abnormalities.
8. New York Heart Association (NYHA) Functional Classification ≥III.
9. Other causes of sensorimotor neuropathy (B12 deficiency, Diabetes Mellitus, HIV treated with retroviral medications, thyroid disorders, alcohol abuse, and chronic inflammatory diseases).
10. Co-morbidity anticipated to limit survival to less than 18 months.
11. Patient received an investigational drug/device and/or participated in another clinical investigational study within 60 days before Baseline.