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

NCT ID: NCT05071300

Last Updated: 2025-12-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-04
• Study Completion Date: 2029-08-31

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).

Detailed Description

This is a multicenter, open-label, Phase 3 study in up to approximately 165 participants. Participants will also receive daily supplemental doses of the recommended daily allowance (RDA) of vitamin A. This study will consist of the following periods: less than or equal to (≤) 8-week screening period, a 157-week treatment period, and a 24-week post-treatment evaluation period.

Participants may continue to receive treatment in this study for up to 2 years or until ION-682884 becomes commercially available in the patient's country, whichever occurs earlier.

Conditions

Hereditary Transthyretin-Mediated Amyloid Polyneuropathy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Eplontersen

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

Group Type: EXPERIMENTAL

Eplontersen

Intervention Type: DRUG

Eplontersen will be administered by SC injection.

Interventions

Eplontersen

Eplontersen will be administered by SC injection.

Intervention Type: DRUG

Other Intervention Names

AKCEA-TTR-LRx; ION-682884; IONIS-TTR-LRx

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

3. Satisfy the following:

1. 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.

2. 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.

4. Willingness to adhere to vitamin A supplementation per protocol.

Exclusion Criteria

1. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ionis Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Mayo Clinic

Scottsdale, Arizona, United States

Indiana University Health University Hospital

Indianapolis, Indiana, United States

Johns Hopkins University Neurology Research Office

Baltimore, Maryland, United States

Boston University School of Medicine

Boston, Massachusetts, United States

The Neurological Institute of New York

New York, New York, United States

University of North Carolina Hospitals - Neurology Clinic

Chapel Hill, North Carolina, United States

Oregon Health and Science University

Portland, Oregon, United States

University of Washington Medical Center

Seattle, Washington, United States

Hospital Italiano de Buenos Aires

Buenos Aires, , Argentina

Instituto Fleni

Buenos Aires, , Argentina

Hospital El Cruce

San Juan Bautista, , Argentina

Perron Institute for Neurological and Translational Science

Murdoch, Western Australia, Australia

Hospital Universitario Clementino Fraga Filho

Botafogo, Rio de Janeiro, Brazil

Universidade Estadual de Campinas

Campinas, , Brazil

Instituto de Neurologia de Curitiba

Curitiba, , Brazil

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto

São Paulo, , Brazil

Vancouver General Hospital

Vancouver, British Columbia, Canada

Toronto General Hospital

Toronto, Ontario, Canada

The Cyprus Institute of Neurology and Genetics

Égkomi, , Cyprus

Centre Hospitalier Universitaire de Toulouse

Toulouse, Haute-Garonne, France

Hôpital de la Timone

Marseille, , France

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

Milan, , Italy

Fondazione IRCCS Policlinico San Matteo

Pavia, , Italy

Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria

Lisbon, , Portugal

Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio

Porto, , Portugal

Hospital Clínico San Carlos

Madrid, , Spain

Hospital Son Llàtzer

Palma de Mallorca, , Spain

Norrlands Universitetssjukhus

Umeå, , Sweden

China Medical University Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Taipei Veterans General Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital

Taoyuan District, , Taiwan

Istanbul Üniversitesi - Istanbul Tip Fakültesi

Istanbul, , Turkey (Türkiye)

Countries

United States; Argentina; Australia; Brazil; Canada; Cyprus; France; Italy; Portugal; Spain; Sweden; Taiwan; Turkey (Türkiye)

Other Identifiers

2024-511201-32-00

Identifier Type: CTIS

Identifier Source: secondary_id

ION-682884-CS13

Identifier Type: -

Identifier Source: org_study_id