CS3 – Phase 3 study in patient with PN
Research type
Research Study
Full title
A Phase 3 Global, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of ION-682884 in Patients with Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
IRAS ID
272360
Contact name
Julian Gillmore
Contact email
Sponsor organisation
Ionis Pharmaceuticals, Inc.
Eudract number
2019-001698-10
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 2 months, days
Research summary
This study is investigating an investigational medication known as ION-682884 in participants with hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN) also known as Familial Amyloid Polyneuropathy. This disease is caused by a mutation or change in a protein called transthyretin (TTR) which can lead to its build up in the nervous system, gastrointestinal tract, kidney and heart.
ION-682884 reduces the level of TTR in the blood. The purpose of this study is to see if the study medication is safe, and in patients with mild or moderate polyneuropathy. Due to the progressive, irreversible, and fatal nature of the disease, this research is important as it may lead to an increase in patients’ and caregiver’s quality of life.
The benefits of ION-6582884 in hATTR-PN patients are yet unknown. Inotersen has been used in hATTR-PN patients and has shown to improve brain function and patient quality of life.
Patients enrolled in the study will receive subcutaneous (under the skin) injections of either ION-682884 or Inotersen. The purpose of the inotersen reference arm is to support comparisons between the ION-682884-CS3 and NEURO-TTR studies. Participants receiving inotersen will eventually receive ION-682884.
This study will involve approximately 140 participants (male and female aged 18-82 years of age) at multiple centres globally.
The study will last about 24 months. Participants will be asked to visit the study centre about 32 times. At each visit, participants will undergo some of the following procedures and tests: physical exams, assessment of vital signs, blood sample tests, urine tests, ECG test and eye exams etc.
Participants will also have the option to take part in a Pharmacokinetic sub-study. Participants can take part in the main study even if they do not wish to take part in the optional sub-study.
The study will be funded by Ionis Pharmaceuticals, Inc.
Research results
Out of the 144 participants who were in the eplontersen group, 135 (94.4%) reached week 66 of the study. Out of the 24 participants in the inotersen group, 20 (83.3%) reached week 66.
The information that was collected (data) showed that eplontersen worked better compared to historical placebo for lowering the amount of TTR protein in the blood. The reduction in TTR protein was about 82% for the eplontersen group and about
11% in the historical placebo group from the NEURO-TTR study. The data also showed that nerve damage in participants who received eplontersen was halted and participants had improved wellbeing (quality of life) when compared with the historical placebo group. Nerve damage was measured by the modified neuropathy
impairment score plus seven (mNIS+7) test and quality of life (QOL) was measured by participants completing the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) questionnaire. The Norfolk QoL-DN includes questions for the person to answer about various aspects of their daily life, such as how well they could perform basic
daily activities, the state of their emotional well-being, and their experiences with social activities. The positive effects seen in participants treated with eplontersen continued through
the end of the study.REC name
East Midlands - Derby Research Ethics Committee
REC reference
20/EM/0005
Date of REC Opinion
6 Mar 2020
REC opinion
Further Information Favourable Opinion