Hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN)
Conditions
Interventions
Experimental: ION-682884
ION-682884 by subcutaneous injection once every 4 weeks
Active Comparator: Inotersen
Inotersen by subcutaneous injection once weekly through week 34. Participants will then c
Sponsors
Viney Nick
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 20 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
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 = 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Change from baseline in mNIS+7 at Week 66 Note: The mNIS+7 composite score is a measure of neurologic impairment that evaluates muscle weakness, sensation, reflexes, nerve conduction, and autonomic function. The mNIS+7 composite score has a range of -22.32 to 346.32, and a higher score indicates lower function. - Change from baseline in the Norfolk Quality of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66 Note: The Norfolk QoL-DN score is a measure of physical function/large fiber neuropathy, symptoms, activities of daily living, small fiber neuropathy, and autonomic neuropathy. The Norfolk QoL-DN total score has a range of -4 to 136, and a higher score indicates poorer quality of life. - Percent change from baseline in serum TTR concentration at Week 66 - Percent change from baseline in serum transthyretin (TTR) concentration at Week 35 - Change from baseline in modified neuropathy impairment score plus 7 (mNIS+7) at Week 35 | — |
Secondary
| Measure | Time frame |
|---|---|
| - Change from baseline in Norfolk QOL-DN at Week 35 - Change from baseline in Neuropathy Symptom and Change (NSC) score at Weeks 35 and 66 Note: NSC score is a questionnaire composed of 38 questions that assess the presence and severity of these neuropathy symptoms (including weakness, loss of temperature and pain sensation, and manifestations associated with autonomic nervous system dysfunction). - Change from baseline in the Physical Component Summary (PCS) score of the 36-Item Short Form Survey (SF-36) at Week 65 Note; The SF-36 is composed of 8 multi-item scales (35 items) assessing physical function (10 items), role limitations due to physical health problems (4 items), bodily pain (2 items), general health (5 items), vitality (4 items), social functioning (2 items), role limitations due to emotional problems (3 items) and emotional well-being (5 items). Each of the 8 scales is scored from 0 to 100 with higher scores indicating better health. The 8 scales can be aggregated into a PCS score, which is also scaled from 0 to 100 with higher scores indicating better health. - Change from baseline in Polyneuropathy Disability (PND) score at Week 65 Note: The PND is a 6-stage scoring system: Stage 0: no impairment; Stage 1: sensory disturbances but preserved walking capabilities; Stage 2: impaired walking capacity, but ability to walk without a stick or crutches; Stage 3A/B: walking with help of 1 or 2 sticks or crutches; Stage 4: confined to wheel chair or bedridden. - Change from baseline in modified body mass index (mBMI) at Week 65 Note: mBMI is defined as body mass index in kilograms per square meter (kg/m^2) multiplied by serum albumin in grams per liter (g/L) | — |
Countries
Brazil, Cyprus, France, Germany, Italy, Japan, New Zealand, Portugal, Spain, Sweden, Taiwan, United States
Contacts
Public ContactClinical Contact
ICON Clinical Research GK
Outcome results
None listed