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
Eplontersen: Eplontersen will be administered by SC injection.
Study 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).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
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
Trial sites (33)
Facility
City
Region
Status
Mayo Clinic
Scottsdale
Arizona
Indiana University Health University Hospital
Indianapolis
Indiana
Johns Hopkins University Neurology Research Office
Baltimore
Maryland
Boston University School of Medicine
Boston
Massachusetts
The Neurological Institute of New York
New York
New York
University of North Carolina Hospitals - Neurology Clinic
Chapel Hill
North Carolina
Oregon Health and Science University
Portland
Oregon
University of Washington Medical Center
Seattle
Washington
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
Hospital Universitario Clementino Fraga Filho
Botafogo
Rio de Janeiro
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
Toronto General Hospital
Toronto
Ontario
The Cyprus Institute of Neurology and Genetics
Égkomi
Cyprus
Centre Hospitalier Universitaire de Toulouse
Toulouse
Haute-Garonne
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
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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