Clinical trial NCT05071300: 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
Official title: An Open-Label, Extension Study to Assess the Long-Term Safety and Efficacy of ION-682884 in Patients With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
Keywords: ION-682884
hATTR-PN
TTR
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-10-08
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in Platelet Count
timeFrame: Baseline to Week 181
measure: Number of Participants With Clinically Significant Changes From Baseline in Renal Function
timeFrame: Baseline to Week 181
measure: Number of Participants with Clinically Significant Changes from Baseline in Transaminases
timeFrame: Baseline to Week 181
measure: Change From Baseline in Adverse Events
timeFrame: Baseline to Week 181
measure: Change From Baseline in Number of Concomitant Medications Used
timeFrame: Baseline to Week 181
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
timeFrame: Baseline to Week 181
measure: Change From Baseline in Body Weight
timeFrame: Baseline to Week 181
measure: Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings
timeFrame: Baseline to Week 181
measure: Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests
timeFrame: Baseline to Week 181
measure: Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters
timeFrame: Baseline to Week 181
measure: Number of Participants With Clinically Significant Changes From Baseline in Thyroid Panel Tests
timeFrame: Baseline to Week 181
measure: Number of Participants With Clinically Significant Changes From Baseline in Coagulation Tests
timeFrame: Baseline to Week 181
measure: Number of Participants With Clinically Significant Changes From Baseline in Inflammatory Panel Tests
timeFrame: Baseline to Week 181
measure: Number of Participants With Clinically Significant Changes From Baseline in Complement and Immunogenicity Tests
timeFrame: Baseline to Week 181
Secondary outcomes:
measure: Change From Baseline in Neuropathy Impairment Score (NIS)
timeFrame: Baseline to Week 181
measure: Change From Baseline in Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) Questionnaire
timeFrame: Baseline to Week 181
measure: Change From Baseline in Neuropathy Symptom and Change Score (NSC)
timeFrame: Baseline to Week 181
measure: Change From Baseline in Serum Transthyretin (TTR) Concentration
timeFrame: Baseline to Week 181
measure: Change From Baseline in Physical Component Summary Score (PCS) of 36-Item Short Form Survey (SF-36)
timeFrame: Baseline to Week 181
measure: Change From Baseline in Polyneuropathy Disability Score (PND)
timeFrame: Baseline to Week 181
measure: Change From Baseline in Modified Body Mass Index (mBMI)
timeFrame: Baseline to Week 181
measure: Change From Baseline in Composite Autonomic Symptom Score-31 (COMPASS-31)
timeFrame: Baseline to Week 181
measure: Change From Baseline in 5 Level EQ-5D (EQ-5D-5L)
timeFrame: Baseline to Week 181
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University Neurology Research Office
state: Maryland
city: Boston
country: United States
facility: Boston University School of Medicine
state: Massachusetts
city: New York
country: United States
facility: The Neurological Institute of New York
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals - Neurology Clinic
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Buenos Aires
country: Argentina
facility: Instituto Fleni
city: Florencio Varela
country: Argentina
facility: Hospital El Cruce
city: Murdoch
country: Australia
facility: Perron Institute for Neurological and Translational Science
state: Western Australia
city: Botafogo
country: Brazil
facility: Hospital Universitario Clementino Fraga Filho
state: Rio De Janeiro
city: Campinas
country: Brazil
facility: Universidade Estadual de Campinas
city: Curitiba
country: Brazil
facility: Instituto de Neurologia de Curitiba
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Égkomi
country: Cyprus
facility: The Cyprus Institute of Neurology and Genetics
city: Toulouse
country: France
facility: Centre Hospitalier Universitaire de Toulouse
state: Haute-Garonne
city: Marseille
country: France
facility: Hôpital de la Timone
city: Milano
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Fondazione Istituto Neurologico Carlo Besta
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário do Porto - Hospital Geral de Santo Antonio
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Palma De Mallorca
country: Spain
facility: Hospital Son Llàtzer
city: Umeå
country: Sweden
facility: Norrlands Universitetssjukhus
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Istanbul
country: Turkey
facility: Istanbul Üniversitesi - Istanbul Tip Fakültesi
Study officials:
References: