Phase 3
N=168
NEURO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
Bottom Line
View on ClinicalTrials.gov: NCT04136184 ↗Enrolled (actual)
168
Serious AEs
17.5%
Results posted
Dec 2024
Primary outcome: Primary: Change From Baseline in Modified Neuropathy Impairment Score Plus 7 (mNIS+7) at Week 66 — 0.2964; 25.0557 scores on a scale — p=0.00000001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Inotersen (Drug); Eplontersen (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Ionis Pharmaceuticals, Inc.
- Primary completion
- Apr 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Modified Neuropathy Impairment Score Plus 7 (mNIS+7) at Week 66 |
0.2964; 25.0557 | 0.00000001 sig |
| PRIMARY Change From Baseline in the Norfolk Quality of Life Diabetic Neuropathy (QoL-DN) Questionnaire at Week 66 |
-5.4964; 14.2388 | 0.00000001 sig |
| PRIMARY Percent Change From Baseline in Serum TTR Concentration at Week 65 |
-81.65; -11.24 | 0.00000001 sig |
| PRIMARY Percent Change From Baseline in Serum TTR Concentration at Week 35 |
-81.14; -14.49 | 0.00000001 sig |
| PRIMARY Change From Baseline in Modified Neuropathy Impairment Score Plus 7 (mNIS+7) at Week 35 |
0.6795; 10.0337 | 0.00012203 sig |
| SECONDARY Change From Baseline in Norfolk QOL-DN at Week 35 |
-3.6306; 8.1896 | 0.00001873 sig |
| SECONDARY Change From Baseline in Neuropathy Symptom and Change (NSC) Score at Weeks 35 and 66 |
0.79; 4.73; -0.03; 8.18 | 0.00052447 sig |
| SECONDARY Change From Baseline in the Physical Component Summary (PCS) Score of the 36-Item Short Form Survey (SF-36) at Week 65 |
0.851; -4.455 | 0.00000558 sig |
| SECONDARY Change From Baseline in Polyneuropathy Disability (PND) Score at Week 65 |
0.1; 0.3 | 0.02407897 sig |
| SECONDARY Change From Baseline in Modified Body Mass Index (mBMI) at Week 65 |
-8.0655; -90.7645 | 0.00000020 sig |
Summary
The main objective of this study was to evaluate the efficacy of eplontersen as compared with the historical control of the placebo cohort in the NEURO-TTR trial (NCT01737398/2012-001831-30), in subjects with hereditary transthyretin-mediated amyloidosis polyneuropathy (hATTR-PN). For more information, please visit http://www.neuro-ttransform.com/.
Eligibility Criteria
Key Inclusion Criteria
- Aged 18 to 82 years at the time of informed consent
- Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal or abstinent
- Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential, the participant or the participantss non-pregnant female partner must be using a highly effective contraceptive method
- 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 Neuropathy Impairment Score (NIS) ≥ 10 and ≤ 130
Key Exclusion Criteria
- Clinically-significant (CS) abnormalities in medical history, screening laboratory results, physical or physical examination that would render a participants unsuitable for inclusion, including but not limited to abnormal safety labs
- Karnofsky performance status ≤ 50
- Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease), including uncontrolled diabetes
- Prior liver transplant or anticipated liver transplant within 1-yr of Screening
- New York Heart Association (NYHA) functional classification of ≥ 3
- Acute coronary syndrome within 6 months of screening or major surgery within 3 months of Screening
- Other types of amyloidosis
- Have any other conditions, which, in the opinion of the Investigator or Sponsor would make the participant unsuitable for inclusion, or could interfere with the participant participating in or completing the Study
- 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
- Previous treatment with Tegsedi™ (Inotersen) or Onpattro™ (patisiran), or other oligonucleotide or RNA therapeutic (including siRNA)
Data sourced from ClinicalTrials.gov (NCT04136184). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.