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


  • Hereditary Transthyretin-Mediated Amyloid Polyneuropathy


Eligible Ages
Between 18 Years and 82 Years
Eligible Genders
Accepts Healthy Volunteers

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)

Study Design

Phase 3
Study Type
Intervention Model
Crossover Assignment
Primary Purpose
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
AKCEA-TTR-LRx by subcutaneous injection once every 4 weeks
  • Drug: AKCEA-TTR-LRx
    AKCEA-TTR-LRx by subcutaneous injection
    Other names:
    • ION-682884
Active Comparator
Inotersen by subcutaneous injection once weekly through week 34. Participants will then convert to AKCEA-TTR-LRx administered subcutaneously once every 4 weeks until the end of study
  • Drug: AKCEA-TTR-LRx
    AKCEA-TTR-LRx by subcutaneous injection
    Other names:
    • ION-682884
  • Drug: Inotersen
    Inotersen by subcutaneous injection
    Other names:
    • ISIS 420915

Recruiting Locations

Boston University School of Medicine
Boston, Massachusetts 02118

More Details

Ionis Pharmaceuticals, Inc.

Study Contact

Ionis Pharmaceuticals

Detailed Description

This is a multicenter, open-label study in up to 140 participants, who will be randomized to receive subcutaneous (SC) injections of either AKCEA-TTR-LRx once every 4 weeks or inotersen once a week. Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A. Participants included in the inotersen reference arm will be crossed over to AKCEA-TTR-LRx at Week 37 after completing the Week 35 assessments.