An Open-Label, Extension Study to Assess the Long-Term Safety and Efficacy of ION-682884 in Patients With Hereditary Transthyretin-Mediated Amyloid Polyneuropathy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 140
- 试验地点
- 33
- 主要终点
- Change From Baseline in Platelet Count
研究概览
简要总结
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).
详细描述
This is a multicenter, open-label, Phase 3 study in up to approximately 140 participants. Eligible participants will receive Eplontersen once every 4 weeks for up to 157 weeks. 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 weeks treatment period, and a 24-week post-treatment evaluation period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Eplontersen
Eplontersen will be administered by subcutaneous (SC) injection once every 4 weeks for up to 3 years (157 weeks).
干预措施: Eplontersen (Drug)
结局指标
主要结局
Change From Baseline in Platelet Count
时间窗: Baseline to Week 181
Number of Participants With Clinically Significant Changes From Baseline in Renal Function
时间窗: Baseline to Week 181
Number of Participants with Clinically Significant Changes from Baseline in Transaminases
时间窗: Baseline to Week 181
Change From Baseline in Adverse Events
时间窗: Baseline to Week 181
Change From Baseline in Number of Concomitant Medications Used
时间窗: Baseline to Week 181
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
时间窗: Baseline to Week 181
Change From Baseline in Body Weight
时间窗: Baseline to Week 181
Number of Participants With Clinically Significant Changes From Baseline in Physical Examination Findings
时间窗: Baseline to Week 181
Number of Participants With Clinically Significant Changes From Baseline in Clinical Laboratory Tests
时间窗: Baseline to Week 181
Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Parameters
时间窗: Baseline to Week 181
Number of Participants With Clinically Significant Changes From Baseline in Thyroid Panel Tests
时间窗: Baseline to Week 181
Number of Participants With Clinically Significant Changes From Baseline in Coagulation Tests
时间窗: Baseline to Week 181
Number of Participants With Clinically Significant Changes From Baseline in Inflammatory Panel Tests
时间窗: Baseline to Week 181
Number of Participants With Clinically Significant Changes From Baseline in Complement and Immunogenicity Tests
时间窗: Baseline to Week 181
次要结局
- Change From Baseline in Neuropathy Symptom and Change Score (NSC)(Baseline to Week 181)
- Change From Baseline in Neuropathy Impairment Score (NIS)(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)
- Change From Baseline in Polyneuropathy Disability Score (PND)(Baseline to Week 181)
- Change From Baseline in Modified Body Mass Index (mBMI)(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 Serum Transthyretin (TTR) Concentration(Baseline to Week 181)
- Change From Baseline in Composite Autonomic Symptom Score-31 (COMPASS-31)(Baseline to Week 181)
- Change From Baseline in 5 Level EQ-5D (EQ-5D-5L)(Baseline to Week 181)