An Extension Study to Assess the Long-Term Safety, Tolerability, Pharmacokinetics, and Effect on Disease Progression of BIIB067 Administered to Previously Treated Adults With Amyotrophic Lateral Sclerosis Caused by Superoxide Dismutase 1 Mutation
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Biogen
- 入组人数
- 139
- 试验地点
- 2
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)
研究概览
简要总结
The primary objective of the study is to evaluate the long-term safety and tolerability of BIIB067 (tofersen) in participants with amyotrophic lateral sclerosis (ALS) and confirmed superoxide dismutase 1 (SOD1) mutation. The secondary objectives are to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), biomarker effects, and efficacy of BIIB067 administered to participants with ALS and a confirmed SOD1 mutation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Must have diagnosis of superoxide dismutase 1-amyotrophic lateral sclerosis (SOD1-ALS), and must have completed the End of Study Visit for either Parts A, B, or C of Study 233AS101 (NCT02623699) (i.e., were not withdrawn).
- •If taking riluzole, participant must be receiving a stable dose for ≥30 days prior to Day
- •If taking edaravone, participant must have initiated edaravone ≥60 days (2 treatment cycles) prior to Day
- •Edaravone may not be administered on dosing days during this study.
- •Medically able to undergo the study procedures, and to adhere to the visit schedule at the time of study entry, as determined by the Investigator.
- •For female participants of childbearing potential must agree to practice effective contraception during the study and be willing and able to continue contraception for 5 months after their last dose of study treatment.
- •Participants from Study 233AS101 Parts A and B must have a washout ≥16 weeks between the last dose of study treatment received in Study 233AS101 and the first dose of BIIB067 received in the current Study 233AS
排除标准
- •History of allergies to a broad range of anesthetics.
- •Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a participant at an increased risk for bleeding during or after a Lumbar Puncture (LP) procedure. These risks could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand's disease, liver disease).
- •Presence of an implanted shunt for the drainage of CSF or an implanted central nervous system (CNS) catheter.
- •Prior or current treatment with small interfering ribonucleic acid (RNA), stem cell therapy, or gene therapy.
- •Treatment with another investigational drug, biological agent (excluding BIIB067), or device within 1 month or 5 half-lives of study agent, whichever is longer.
- •Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system (DPS) during the study period.
- •Current or recent (within 1 month) use, or anticipated need, in the opinion of the Investigator, of copper (II) (diacetyl-bis(N4-methylthiosemicarbazone)) or pyrimethamine.
- •Female participants who are pregnant or currently breastfeeding.
- •Current enrollment in any other interventional study.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
BIIB067
Participants who have completed Parts A, B, or C of study 233AS101 will be placed in this arm.
干预措施: Tofersen (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious AEs (TESAEs)
时间窗: From first dose of the study drug in the current study up to end of follow-up period (up to Week 364)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. An SAE is any untoward medical occurrence that at any dose results in death, life-threatening event, requires inpatient hospitalization, significant disability/incapacity or congenital anomaly. TEAEs were defined as any AEs or SAE with an onset date and time that was on or after the first dose of study drug, or any pre-existing condition that worsened in severity after the first dose of study drug.
次要结局
- Concentration of BIIB067 in Cerebrospinal Fluid (CSF)(Week 4)
- 233AS101 and 233AS102 ISE: Neurofilament Light Chain (NfL) Plasma Concentration Ratio to Baseline(Baseline, Weeks 52, 104 and 148)
- Plasma Concentration of BIIB067(Week 4)
- 233AS101 and 233AS102 ISE: Change From Baseline in Total Amyotropic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R) Score(Baseline, Weeks 52, 104 and 148)
- 233AS101 and 233AS102 ISE: Change From Baseline in Individual Muscle Strength Assessed by HHD(Baseline, Weeks 52, 104 and 148)
- 233AS101 and 233AS102 Integrated Summary of Efficacy (ISE): Total CSF Superoxide Dismutase 1 (SOD1) Protein Ratio to Baseline(Baseline, Weeks 52, 104 and 148)
- 233AS101 and 233AS102 ISE: Change From Baseline in Percent Predicted Slow Vital Capacity (SVC)(Baseline, Weeks 52, 104 and 148)
- 233AS101 and 233AS102 ISE: Change From Baseline in Handheld Dynamometry (HHD) Overall Megascore(Baseline, Weeks 52, 104 and 148)
- 233AS101 and 233AS102 ISE: Time to Death or Permanent Ventilation(From the baseline of the study 233AS101 up to the end of the follow-up period of the current study (up to Week 364))
- 233AS101 and 233AS102 ISE: Time to Death(From the baseline of the study 233AS101 up to the end of the follow-up period of the current study (up to Week 364))