Eplontersen for Amyloid Neuropathy

Not currently recruiting at 40 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests eplontersen, a treatment for hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN), a condition affecting the nerves that can cause numbness or weakness. The researchers aim to assess the treatment's safety and tolerability over an extended period. Participants will receive injections every four weeks for up to three years. This trial suits those who have completed specific related studies and have been diagnosed with hATTR-PN. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

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.

Is there any evidence suggesting that eplontersen is likely to be safe for humans?

Research has shown that eplontersen is generally safe for patients with hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN). In earlier studies, patients taking eplontersen experienced fewer side effects than those who took a placebo. The most common side effects were mild, such as redness or swelling at the injection site.

The FDA has approved eplontersen for treating nerve damage in adults with this condition, indicating it has undergone careful safety evaluation. This approval confirms that the treatment has been thoroughly reviewed for safety in this condition.

Overall, current evidence supports the safety of eplontersen, with side effects that most patients can manage. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Eplontersen is unique because it targets amyloid neuropathy by interfering with the production of transthyretin, a protein that can misfold and cause nerve damage. Unlike existing treatments that might focus on managing symptoms or slowing progression, Eplontersen aims to tackle the root cause of the condition by reducing the levels of this problematic protein. Additionally, it is administered through a convenient subcutaneous injection once every four weeks, which could be more manageable for patients compared to more frequent dosing schedules. Researchers are excited about Eplontersen because it offers a novel approach that could significantly improve the quality of life for those affected by amyloid neuropathy.

What evidence suggests that eplontersen might be an effective treatment for amyloid neuropathy?

Research has shown that eplontersen, the treatment under study in this trial, may help treat hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN). In earlier studies, eplontersen significantly lowered levels of transthyretin, a protein that can misfold and damage nerves in this condition. After 66 weeks, patients consistently experienced improvements in symptoms compared to past data. Regulators have approved the treatment for its effectiveness in addressing nerve problems related to hereditary amyloidosis. This suggests that eplontersen could be a promising option for managing hATTR-PN symptoms. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04136184

NCT04136184 | NEURO-TTRansform: A Study to Evaluate ...

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 ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10540057/

Eplontersen for Hereditary Transthyretin Amyloidosis With ...

Main Outcomes and Measures. Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified ...

3.

astrazeneca.com

astrazeneca.com/media-centre/press-releases/2023/eplontersen-demonstrated-sustained-benefit-in-phase-iii-trial.html

Eplontersen demonstrated sustained benefit in Phase III ...

The positive results from the 66-week analysis of the Phase III NEURO-TTRansform trial show that eplontersen provided consistent and sustained transthyretin ...

4.

astrazeneca-us.com

astrazeneca-us.com/media/press-releases/2023/wainua-eplontersen-granted-first-ever-regulatory-approval-in-the-us-for-the-treatment-of-adults-with-polyneuropathy-of-hereditary-transthyretin-mediated-amyloidosis.html

WAINUA (eplontersen) granted first-ever regulatory ...

US FDA approval based on NEURO-TTRansform Phase III results showing WAINUA demonstrated consistent and sustained benefit improving ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S0147956321001229

P010. Evaluation of the Efficacy and Safety of AKCEA-TTR- ...

The CARDIO-TTRansform trial is a large Phase 3 trial designed to evaluate the clinical efficacy and safety of AKCEA-TTR-LRx compared to placebo in patients ...

6.

astrazeneca.com

astrazeneca.com/media-centre/press-releases/2023/wainua-eplontersen-granted-first-ever-regulatory-approval-us-treatment-of-adults-with-polyneuropathy-hereditary-transthyretin-mediated-amyloidosis.html

Wainua (eplontersen) granted first-ever regulatory ...

US FDA approval based on NEURO-TTRansform Phase III results showing Wainua demonstrated consistent and sustained benefit improving ...

7.

tandfonline.com

tandfonline.com/doi/full/10.1080/13506129.2024.2427290

Full article: Effects of eplontersen on symptoms ...

The NEURO-TTRansform trial showed that after 66 weeks of treatment, eplontersen significantly reduced neuropathic impairment and improved quality of life (QoL)