Eplontersen for Amyloid Neuropathy

Recruiting at 33 trial locations

Overseen By Ionis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ionis Pharmaceuticals, Inc.

Disqualifiers: New or worsening conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 157 weeks

151 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing the safety of Eplontersen, a medication given regularly, in patients with a genetic condition that causes nerve damage. The treatment works by lowering harmful protein levels to reduce nerve damage.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Eplontersen for treating amyloid neuropathy?

Eplontersen is being studied in a phase 3 trial for its ability to treat hereditary transthyretin amyloidosis with polyneuropathy, a severe disease caused by protein deposits in the body. Similar treatments, like tafamidis, have shown effectiveness in slowing disease progression, suggesting that Eplontersen may also be beneficial. ^{1 2 3 4 5}

Is Eplontersen safe for humans?

Eplontersen, also known as ION-682884, is being studied for its safety in humans in a phase 3 clinical trial for hereditary transthyretin amyloidosis with polyneuropathy. While specific safety data from this trial is not detailed in the available research, the ongoing study suggests that it is being carefully evaluated for safety in humans. ^{1 3 4 6 7}

How is the drug Eplontersen different from other treatments for amyloid neuropathy?

Eplontersen is unique because it is an antisense oligonucleotide that targets and degrades the messenger RNA (mRNA) responsible for producing transthyretin (TTR) protein, which is involved in amyloid neuropathy. This approach is different from other treatments like tafamidis, which stabilize the TTR protein rather than reducing its production. ^{1 3 4 7 8}

Eligibility Criteria

This trial is for adults with hereditary transthyretin-mediated amyloid polyneuropathy who have completed certain previous studies. Participants must agree to vitamin A supplementation, use contraception if fertile, and be able to follow study requirements. Pregnant or breastfeeding women are excluded.

Inclusion Criteria

I am willing to follow the vitamin A supplement plan.

Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements

I am a man following specific guidelines to prevent pregnancy during the trial.

Exclusion Criteria

Have any new condition or worsening of existing condition that in the opinion of the Investigator or Sponsor would make the participant unsuitable for enrollment or could interfere with the participant taking part in or completing the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

≤ 8 weeks

Treatment

Participants receive eplontersen by subcutaneous injection once every 4 weeks, along with daily vitamin A supplementation

157 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Open-label extension

Participants may continue to receive treatment until the drug becomes commercially available in their country

Up to 2 years

Treatment Details

Interventions

• Eplontersen

Trial Overview The trial tests the long-term safety and effectiveness of Eplontersen in patients with hATTR-PN. It aims to understand how well patients tolerate extended dosing of this medication over a longer period.

Participant Groups

Group I: Eplontersen Experimental Treatment 1 Intervention

Eplontersen will be administered by subcutaneous (SC) injection once every 4 weeks for up to 3 years (157 weeks).

Eplontersen is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as Wainua for:

• Polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults

Approved in European Union as Wainua for:

• Hereditary transthyretin-mediated amyloidosis (ATTRv) and stage 1 or 2 polyneuropathy in adults

Approved in United Kingdom as Wainua for:

• Hereditary transthyretin-mediated amyloidosis (ATTRv) and stage 1 or 2 polyneuropathy in adults

Who Is Running the Clinical Trial?

Ionis Pharmaceuticals, Inc.

Lead Sponsor

Trials

151

Recruited

27,800+

Dr. Brett P. Monia

Ionis Pharmaceuticals, Inc.

Chief Executive Officer since 2020

PhD in Pharmacology from the University of Pennsylvania, BSc in Molecular Biology and Analytical Chemistry from Stockton State College

Dr. Eric Bastings

Ionis Pharmaceuticals, Inc.

Chief Medical Officer

MD

Findings from Research

The NEURO-TTRansform study is evaluating eplontersen, an antisense oligonucleotide aimed at reducing transthyretin (TTR) mRNA, in 168 patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), highlighting its potential as a targeted treatment for this severe disease.

The study population is diverse, with patients aged 18-82 years, predominantly male (69%), and primarily in early stages of the disease, indicating that eplontersen is being tested in a representative cohort reflective of real-world clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen. Coelho, T., Waddington Cruz, M., Chao, CC., et al.[2023]

Eplontersen, an antisense oligonucleotide targeting TTR mRNA, effectively inhibits the production of transthyretin protein, which is crucial for treating transthyretin-mediated amyloidosis, as shown in phase 1 studies with healthy volunteers.

The pharmacokinetic model revealed that factors like lean body mass and injection site (abdomen vs. arm) influence drug absorption and clearance, but these variations do not significantly affect the drug's therapeutic response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic/pharmacodynamic modelling of eplontersen, an antisense oligonucleotide in development for transthyretin amyloidosis. Diep, JK., Yu, RZ., Viney, NJ., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

A selective transthyretin-adsorption column for the treatment of patients with familial amyloid polyneuropathy. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of tafamidis treatment on transthyretin (TTR) stabilization, efficacy, and safety in Japanese patients with familial amyloid polyneuropathy (TTR-FAP) with Val30Met and non-Val30Met: A phase III, open-label study. [2016]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Characteristics of Patients with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an Open-label Phase 3 Study of Eplontersen. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Current and future treatment of amyloid neuropathies. [2014]

6. England pubmed.ncbi.nlm.nih.gov

CSP-1103 (CHF5074) stabilizes human transthyretin in healthy human subjects. [2018]

7. England pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic/pharmacodynamic modelling of eplontersen, an antisense oligonucleotide in development for transthyretin amyloidosis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

mNIS+7 and lower limb function in inotersen treatment of hereditary transthyretin-mediated amyloidosis. [2020]