NEURO-TTRansform: A Study to Evaluate the Efficacy and Safety of AKCEA-TTR-LRx in Participants With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy

To evaluate the efficacy and safety of AKCEA-TTR-LRx 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/.

Inclusion Criteria:

1. Aged 18 to 82 years at the time of informed consent

2. Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent

3. Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the subject or the subject's non-pregnant female partner must be using a highly effective contraceptive method

4. Diagnosis of hereditary transthyretin-mediated polyneuropathy as defined by meeting all 3 of the following:

- Stage 1 or Stage 2 Familial Amyloid Polyneuropathy (FAP) or Coutinho Stage

- Documented genetic mutation in the TTR gene

- Symptoms and signs consistent with neuropathy associated with transthyretin amyloidosis, including NIS ≥ 10 and ≤ 130

Exclusion Criteria:

1. Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a subject unsuitable for inclusion, including but not limited to abnormal safety labs

2. Karnofsky performance status ≤ 50

3. Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease), including uncontrolled diabetes

4. Prior liver transplant or anticipated liver transplant within 1-yr of Screening

5. New York Heart Association (NYHA) functional classification of ≥ 3

6. Acute coronary syndrome within 6 months of screening or major surgery within 3 months of Screening

7. Other types of amyloidosis

8. Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study

9. Current treatment with any approved drug for hereditary TTR amyloidosis such as Vyndaqel® / Vyndamax™ (tafamidis), Tegsedi™ (inotersen), Onpattro™ (patisiran), off-label use of diflunisal or doxycycline, and tauroursodeoxycholic acid (TUDCA). If previously treated with Vyndaqel® / Vyndamax™, diflunisal or doxycycline, and TUDCA, must have discontinued treatment for at least 2 weeks prior to Study Day 1

10. Previous treatment with Tegsedi™ (Inotersen) or Onpattro™ (patisiran), or other oligonucleotide or RNA therapeutic (including siRNA)

Conditions:
• Polyneuropathies
• Amyloid Neuropathies
• Amyloidosis