Hereditary Transthyretin-Mediated Amyloid Polyneuropathy MedDRA version: 20.0 Level: LLT Classification code 10057949 Term: Familial amyloid polyneuropathy System Organ Class: 100000004850
Conditions
Sponsors
Ionis Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Satisfactory completion of ION-682884-CS3 as judged by the Investigator and Sponsor, OR diagnosis of hATTR-PN and satisfactory completion of study ISIS 420915-CS101 (an Investigator-Sponsored study with inotersen - the unconjugated version of ION-682884) 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: a. 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 FSH levels in the postmenopausal range for the laboratory involved) - Abstinent*or - If engaged in sexual relations of child-bearing potential, agree to use highly effective contraceptive methods (Section 6.4.1) from the time of signing the informed consent form until at least 24 weeks after the last dose of ION-682884 and agree to receive pregnancy tests per protocol b. Males: Surgically sterile (i.e., bilateral orchidectomy) or abstinent*, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), the patient’s non-pregnant female partner must use a highly effective contraceptive method (Section 6.4.1) from the time of signing the informed consent form until at least 24 weeks after the last dose of ION-682884 *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 patient. 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 116 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 52
Exclusion criteria
Exclusion criteria: 1. Have any new condition or worsening of existing condition that in the opinion of the Investigator or Sponsor would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the safety and tolerability of extended dosing with ION-682884 (eplontersen) in patients with hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN).;Secondary Objective: The secondary objective is to evaluate the efficacy of extended dosing with ION-682884.;Primary end point(s): The primary endpoints (PEP) are change from Baseline (Index Study Baseline and separately open-label extension [OLE] Baseline) in the following measures: • Platelet count, renal function and transaminases • Adverse events (AE) • Use of concomitant medications • Vital signs and weight • Physical examination findings • Clinical laboratory tests • Electrocardiogram (ECG) parameters • Thyroid panel tests • Coagulation tests • Inflammatory panel tests • Complement and immunogenicity tests;Timepoint(s) of evaluation of this end point: The primary endpoints (PEP) are change from Baseline (Index Study Baseline and separately open-label extension [OLE] Baseline) in the following measures: • Platelet count and renal function • Adverse events (AE) • Use of concomitant medications • Vital signs and weight • Physical examination findings • Clinical laboratory tests • Electrocardiogram (ECG) parameters • Thyroid panel tests • Coagulation tests • Inflammatory panel tests • Complement and immunogenicity tests | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are Change from Baseline (Index Study Baseline and separately OLE Baseline) in the following measures: • Neuropathy Impairment Score (NIS) • Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire • Neuropathy Symptom and Change score (NSC) • Serum Transthyretin (TTR) concentration • Physical Component Summary score (PCS) of 36-Item Short Form Survey (SF-36) • Polyneuropathy disability score (PND) • Modified body mass index (mBMI) • Composite Autonomic Symptom Score-31 (COMPASS-31) • 5 Level EQ-5D (EQ-5D-5L);Timepoint(s) of evaluation of this end point: The secondary endpoints are Change from Baseline (Index Study Baseline and separately OLE Baseline) in the following measures: • Neuropathy Impairment Score (NIS) • Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire • Neuropathy Symptom and Change score (NSC) • Serum Transthyretin (TTR) concentration • Physical Component Summary score (PCS) of 36-Item Short Form Survey (SF-36) • Polyneuropathy disability score (PND) • Modified body mass index (mBMI) • Composite Autonomic Symptom Score-31 (COMPASS-31) • 5 Level EQ-5D (EQ-5D-5L) | — |
Countries
Argentina, Australia, Brazil, Canada, Cyprus, France, Germany, Italy, New Zealand, Portugal, Spain, Sweden, Taiwan, Turkey, United States
Contacts
Public ContactIonis Clinical Trial Information
Ionis Pharmaceuticals, Inc.
Outcome results
None listed