A Study to Assess the Long-Term Safety and Efficacy of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Patients With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy

NCT05071300 | Active Not Recruiting Phase 3 FDA Drug

• 2 other identifiers: ION-682884-CS132024-511201-32-00
• Study Type: interventional
• Target: 151
• Locations: 13 countries
• Sites: 33

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of extended dosing with eplontersen in participants with hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN).

Conditions

Hereditary Transthyretin-Mediated Amyloid Polyneuropathy

Keywords

ION-682884; hATTR-PN; TTR

Outcome Measures

Primary Outcomes (14)

• Change From Baseline in Platelet Count

  Baseline to Week 181

• Number of Participants With Clinically Significant Changes From Baseline in Renal Function

  Baseline to Week 181

• Number of Participants with Clinically Significant Changes from Baseline in Transaminases

  Baseline to Week 181

• Change From Baseline in Adverse Events

  Baseline to Week 181

• Change From Baseline in Number of Concomitant Medications Used

  Baseline to Week 181

• Number of Participants With Clinically Significant Changes From Baseline in Vital Signs

  Baseline to Week 181

• Change From Baseline in Body Weight

  Baseline to Week 181

• Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings

  Baseline to Week 181

• Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests

  Baseline to Week 181

• Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters

  Baseline to Week 181

• Number of Participants With Clinically Significant Changes From Baseline in Thyroid Panel Tests

  Baseline to Week 181

• Number of Participants With Clinically Significant Changes From Baseline in Coagulation Tests

  Baseline to Week 181

• Number of Participants With Clinically Significant Changes From Baseline in Inflammatory Panel Tests

  Baseline to Week 181

• Number of Participants With Clinically Significant Changes From Baseline in Complement and Immunogenicity Tests

  Baseline to Week 181

Secondary Outcomes (9)

• Change From Baseline in Neuropathy Impairment Score (NIS)

  Baseline to Week 181

• Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) Questionnaire

  Baseline to Week 181

• Change From Baseline in Neuropathy Symptom and Change Score (NSC)

  Baseline to Week 181

• Change From Baseline in Serum Transthyretin (TTR) Concentration

  Baseline to Week 181

• Change From Baseline in Physical Component Summary Score (PCS) of 36-Item Short Form Survey (SF-36)

  Baseline to Week 181

Study Arms (1)

Eplontersen

EXPERIMENTAL

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

Drug: Eplontersen

Interventions

Eplontersen DRUG

Eplontersen will be administered by SC injection.

Also known as: AKCEA-TTR-LRx, ION-682884, IONIS-TTR-LRx

Eplontersen

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Satisfactory completion of ION-682884-CS3 (NCT04136184) (Index Study) as judged by the Investigator and Sponsor, or diagnosis of hATTR-PN and satisfactory completion of either study ISIS 420915-CS101 or study 2018-P001436 (NCT03702829) (both are Investigator-Sponsored studies with inotersen - the unconjugated version of eplontersen) as judged by the Investigator and Sponsor.
• 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.
• Satisfy the following:
• Females: must be non-pregnant and non-lactating and either:
• Surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy);
• Post-menopausal (defined as 12 months of spontaneous amenorrhea in females \> 55 years of age or, in females ≤ 55 years, 12 months of spontaneous amenorrhea without an alternative medical cause and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory involved;
• Abstinent\*;
• If engaged in sexual relations of child-bearing potential, agree to use highly effective contraceptive methods from the time of signing the informed consent form until at least 24 weeks after the last dose of eplontersen and agree to receive pregnancy tests per protocol.
• Males: Surgically sterile (i.e., bilateral orchidectomy) or abstinent\*, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), the participant or the participant's non-pregnant female partner must use a highly effective contraceptive method from the time of signing the informed consent form until at least 24 weeks after the last dose of eplontersen. \*Abstinence (i.e., refraining from heterosexual intercourse throughout the duration of study participation) is only acceptable as true abstinence, i.e., when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of a trial and withdrawal are not acceptable methods of contraception.
• Willingness to adhere to vitamin A supplementation per protocol.

You may not qualify if:

• \. 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.

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (33)

Mayo Clinic

Scottsdale, Arizona, 85259, United States

Location

Indiana University Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University Neurology Research Office

Baltimore, Maryland, 21287, United States

Location

Boston University School of Medicine

Boston, Massachusetts, 02118, United States

Location

The Neurological Institute of New York

New York, New York, 10032, United States

Location

University of North Carolina Hospitals - Neurology Clinic

Chapel Hill, North Carolina, 27514, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1199ABB, Argentina

Location

Instituto Fleni

Buenos Aires, C1428 AQK, Argentina

Location

Hospital El Cruce

San Juan Bautista, 1888, Argentina

Location

Perron Institute for Neurological and Translational Science

Murdoch, Western Australia, 6150, Australia

Location

Hospital Universitario Clementino Fraga Filho

Botafogo, Rio de Janeiro, 22281-100, Brazil

Location

Universidade Estadual de Campinas

Campinas, 13083-888, Brazil

Location

Instituto de Neurologia de Curitiba

Curitiba, 81210-310, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto

São Paulo, 14051-140, Brazil

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G2C4, Canada

Location

The Cyprus Institute of Neurology and Genetics

Égkomi, 2371, Cyprus

Location

Centre Hospitalier Universitaire de Toulouse

Toulouse, Haute-Garonne, 31059, France

Location

Hôpital de la Timone

Marseille, 13385, France

Location

Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Fondazione Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, 27100, Italy

Location

Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria

Lisbon, 1649-035, Portugal

Location

Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio

Porto, 4099-001, Portugal

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Son Llàtzer

Palma de Mallorca, 07198, Spain

Location

Norrlands Universitetssjukhus

Umeå, 901 85, Sweden

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Chang Gung Memorial Hospital

Taoyuan District, 333, Taiwan

Location

Istanbul Üniversitesi - Istanbul Tip Fakültesi

Istanbul, 34093, Turkey (Türkiye)

Location

MeSH Terms

Interventions

eplontersen

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: October 8, 2021
• Study Start: January 4, 2022
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: December 4, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

FR (2); BR (4); IT (2); SE (1); TU (1); AU (1); CY (1); CA (2); PT (2); US (8); ES (2); TW (4); AR (3)