A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of AG10 in Subjects with Symptomatic Transthyretin Amyloid Polyneuropathy (ATTRibute-PN Trial)

1. Be able to understand and sign a written informed consent form, which must
be obtained prior to initiation of study procedures;
2. Be male or female *18 to *90 years of age;
3. Have Stage I or II symptoms (polyneuropathy disability [PND] *IIIa) of
ATTR-PN and an established diagnosis of ATTR-PN as defined by physical exam
findings and/or neurophysiological test findings consistent with the diagnosis
of ATTR-PN;
4. Have an NIS of 5 to 130 (inclusive) during screening;
5. Have a nerve conduction studies (NCS) score [sum of the sural sensory nerve
action potential (SNAP), tibial compound muscle action potential (CMAP), ulnar
SNAP, ulnar CMAP, and peroneal CMAP] of *2 points during screening. NCS is a
component of mNIS+7;
6. Have a mutation consistent with ATTR-PN either documented in medical history
or confirmed by genotyping obtained at Screening prior to randomization. *No
genetic testing is needed for subjects who are recipients of domino liver
transplants;
7. Have an anticipated survival of *2 years, in the opinion of the Investigator;
8. Have Karnofsky performance status *60 %;
9. Have serum albumin levels >3.0 g/dL;
10. Female subjects of childbearing potential who engage in heterosexual
intercourse must agree to use a highly effective method of contraception
beginning with randomization and continuing for 30 days after the last dose of
AG10. A man who is sexually active with a woman of childbearing potential and
has not had a vasectomy must agree to use a barrier method of birth control.
Postmenopausal state female subjects must be confirmed with plasma
follicle-stimulating hormone (FSH) at Screening.

1. Had a prior liver transplantation or is planning to undergo liver
transplantation with a wild-type organ graft as treatment for symptomatic
ATTR-PN during the study period. Note: Recipients of a *domino* liver
transplant from an ATTR-PN donor who have developed ATTR-PN mediated by their
graft are allowed under this protocol, as long as re-transplantation to treat
ATTR-PN is not planned during the study period and meets all other eligibility
criteria;
2. Has sensorimotor or autonomic neuropathy not related to ATTR-PN; for
example, autoimmune disease or monoclonal gammopathy, malignancy, or alcohol
abuse;
3. Has Vitamin B-12 levels below the lower limit of normal (LLN);
4. Has clinical evidence of untreated hyper/hypothyroidism;
5. Has leptomeningeal TTR amyloidosis;
6. Has Type 1 diabetes;
7. Has had Type 2 diabetes for *5 years;
8. Has active hepatitis B or C or known human immunodeficiency virus (HIV)
infection;
9. Has NYHA heart failure classification >Class II;
10. Had acute coronary syndrome, uncontrolled cardiac arrhythmia, or a stroke
within 90 days prior to Screening;
11. Has estimated glomerular filtration rate (eGFR) by Modification of Diet for
Renal Disease (MDRD) formula <30 mL/min/1.73 m2 at Screening;
12. Has abnormal liver function tests at Screening, defined as alanine
aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of
normal (ULN) or total bilirubin >3 × ULN;
13. Had a malignancy within 2 years, except for basal or squamous cell
carcinoma of
the skin or carcinoma in situ of the cervix that has been successfully treated;
14. Has known hypersensitivity to Investigational Medicinal Product (IMP) (AG10
or placebo), its metabolites, or formulation excipients;
15. Is currently undergoing treatment for ATTR-PN with patisiran, inotersen, or
other gene silencing agents, marketed drug products lacking a label indication
for ATTR-PN (e.g., diflunisal, doxycycline), natural products or derivatives
used as unproven therapies for ATTR-PN (e.g., green tea extract,
tauroursodeoxycholic acid [TUDCA]/ursodiol), within 14 days, or 90 days for
patisiran and 180 days for inotersen prior to dosing. Prior to screening,
tafamidis, if already prescribed to potential subjects as part of their
established background therapy, is allowed at the labeled dosage and
administration of 20 mg/day for the treatment of ATTR-PN with, in the opinion
of the Investigator, evidence of disease progression while on tafamidis
treatment;
16. Female subjects who are pregnant or breastfeeding. Breastfeeding females
must agree to discontinue nursing before IMP is administered. A negative urine
pregnancy test at Screening and on Day 1 prior to randomization are required
for female subjects of childbearing potential;
17. In the judgment of the Investigator or Medical Monitor, has any clinically
important ongoing medical condition or laboratory abnormality or other
condition that might jeopardize the subject*s safety, increase their risk from
participation, or interfere with the study;
18. Participation in another investigational drug or investigational device
study within 30 days prior to dosing or 5 half-lives of the investigational
drug, whichever is longer, with potential residual effects that might confound
the results of this study;
19. Has any condition that, in the opinion of the Investigator or Medical
Monitor, would preclude compliance with the study protocol such as a history of
substance abuse, alcoholism, or a psychiatric condition.