2025-523857-32-00招募中3 期
A Phase 3, Randomized, Double-Blinded Study to Evaluate the Safety and Efficacy of Salanersen (BIIB115) After Onasemnogene Abeparvovec Treatment in Infants with Genetically Diagnosed Spinal Muscular Atrophy
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 14
- 试验地点
- 21
- 主要终点
- Parts A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Part A: Up to Day 365]
研究概览
简要总结
To evaluate the safety and tolerability of adding salanersen 6 months after OA in participants with genetically diagnosed SMA who received presymptomatic treatment with OA
研究设计
- 分配方式
- Randomized
- 主要目的
- Part B
- 盲法
- Double (Investigator, Analyst, Monitor, Subject, Carer)
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 否
入选标准
- •1.Genetic documentation of 5q spinal muscular atrophy (SMA) homozygous gene deletion or mutation or compound heterozygous mutation.
- •2.2 copies of the survival motor neuron 2 (SMN2) gene
- •3.Onasemnogene Abeparvovec (OA) dose given at ≤ 42 days of age and screening initiated less than 6 months from OA dosing
- •4.OA dose given while participant was presymptomatic, per Investigator attestation. For this study, presymptomatic is defined as follows: - No clinical signs or symptoms at the time of OA dosing that are, in the opinion of the Investigator, strongly suggestive of SMA. - No absence of tendon reflexes (i.e., absence of all of biceps, knee and ankle tendons) at the time of OA dosing (e.g., Hammersmith Infant Neurological Examination (HINE) Section 1 or equivalent). - If Compound Muscle Action Potential (CMAP) data is available at the time of dosing, ulnar CMAP amplitude ≥ 2 millivolt (mV).
- •5.Note: Other protocol-defined inclusion criteria will apply.
排除标准
- •1.Any unresolved post-OA laboratory abnormalities defined as follows: - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be less than 2 × Upper Limit of Normal (ULN) while not receiving corticosteroids within 30 days prior to dosing with salanersen or sham procedure (repeat testing may be performed if necessary). - Evidence of thrombocytopenia, indicated by the platelet count being lower than the normal range for the laboratory. - Evidence of elevated troponin-I levels, identified as elevated post-OA, and has not returned to the normal range.
- •2.Confirmed demonstration of corrected QT interval, using Fridericia’s correction method, of > 450 milliseconds (ms).
- •3.Other than OA, any prior treatment with an approved SMA disease modifying therapy (e.g. nusinersen and/or risdiplam), a myostatin inhibitor therapy, or an investigational drug given for the treatment of SMA.
- •4.Steroid treatment administered for the purpose of treating complications following OA within 14 days prior to dosing with salanersen or sham procedure on Day
- •5.Note: Other protocol-defined exclusion criteria will apply.
研究组 & 干预措施
BIIB115
Test
干预措施: BIIB115 (Drug)
结局指标
主要结局
Parts A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Part A: Up to Day 365]
Parts A: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Part A: Up to Day 365]
次要结局
- 1. Part B: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time Frame: Part B: Up to Day 1825]
- 2. Parts A and B: Change From Baseline in Plasma Levels of Neurofilament Light Chain (NfL) Blood will be collected to characterize changes in plasma NfL following treatment with salanersen. NfL is a protein released from damaged neurons and is a biomarker of neurodegeneration. [Time Frame: Part A: At Days 180 and 365; Part B: Up to Day 1825]
- 3. Parts A and B: Change from Baseline in Compound Muscle Action Potential (CMAP) Amplitudes CMAP is a well-validated method for tracking disease progression in neuromuscular disorders such as SMA and amyotrophic lateral sclerosis and has been proposed as a potential biomarker of a therapeutic effect in SMA.
- 3continued...CMAPs will be performed for the following nerve-muscle pairs: ulnar-abductor digiti minimi and peroneal-tibialis anterior. [Time Frame: Part A: At Day 365 and Part B: Up to Day 1825]
- 4.Parts A and B: Percentage of Participants Attaining World Health Organization (WHO) Motor Milestones. The WHO motor milestones will include six key developmental milestones: sitting without support, standing with assistance, hands-and-knees crawling, walking with assistance, standing alone, and walking alone. [Time Frame: Part A: At Day 365 and Part B: Up to Day 1825]
- 5.Parts A and B: Percentage of Participants Attaining Hammersmith Infant Neurological Examination Section 2 (HINE-2) Motor Milestones Section 2 of the HINE is used to assess motor milestones and includes 8 motor milestone categories: voluntary grasp (0 to 3), ability to kick in supine position (0 to 4), head control (0 to 2), rolling (0 to 3), sitting (0 to 4), crawling (0 to 4), standing (0 to 3), and walking (0 to 3).
- 5continued...Total HINE-2 score is the sum of points from each item and can range from 0 to 26, with higher scores depicting a better level of ability. [Time Frame: Part A: At Day 365 and Part B: Up to Day 1825]
- 6.Parts A and B: Change From Baseline in Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) Motor Function Scale The CHOP INTEND test is designed to evaluate the motor skills of participants with significant motor weakness.
- 14.Parts A and B: Concentration of Salanersen in Serum [Time Frame: Part A: Up to Day 365 and Part B: Up to Day 1825]
- 6continued...It includes 16 items (capturing neck, trunk, and proximal and distal limb strength) structured to move from easiest to hardest with the grading including gravity eliminated (lower scores) to antigravity movements (higher scores). All item scores range from 0-4.
- 6continued...The total score ranges from 0-64, with higher scores depicting better motor function. [Time Frame: Part A: At Day 365 and Part B: Up to Day 1825]
- 7.Parts A and B: Percentage of Participants who Remain Free of Clinically Manifested Spinal Muscular Atrophy (SMA) [Time Frame: Part A: At Day 365 and Part B: At Day 545]
- 8.Part B: Percentage of Participants who Develop Spinal Muscular Atrophy (SMA) Subtypes (Non-Sitters, Sitters and Walkers) as Assessed by the Investigator [Time Frame: Part B: Up to Day 1825]
- 9.Part B: Hammersmith Functional Motor Scale Expanded (HFMSE) Total Score The HFMSE is a tool used to assess motor function in individuals with SMA. Participants will be asked to complete a specific movement and are then graded on the quality and execution of that movement. Higher scores indicate higher levels of motor ability.
- 9Continued...The overall score is the sum of the scores for all 33 items, with a maximum score of 66, with higher scores depicting better ability to perform activities. [Time Frame: Part B: Up to Day 1825]
- 10.Part B: Revised Upper Limb Module (RULM) Total Score The RULM is developed to assess upper limb functional abilities of participants with SMA. This test consists of a total of 20 upper limb performance items that are reflective of activities of daily living. The RULM is scored from 0 to 37 points, with higher scores indicating better function. [Time Frame: Part B: Up to Day 1825]
- 11.Parts A and B: Time to Death (Overall Survival) [Time Frame: Part A: Up to Day 365 and Part B: Up to Day 1825]
- 12.Parts A and B: Time to Death or Permanent Ventilation Permanent ventilation is defined as tracheostomy or ≥16 hours ventilation/day continuously for >21 days in the absence of an acute reversible event. [Time Frame: Part A: Up to Day 365 and Part B: Up to Day 1825]
- 13.Parts A and B: Concentration of Salanersen in Cerebrospinal Fluid (CSF) [Time Frame: Part A: Up to Day 365 and Part B: Up to Day 1460]
研究者
Clinical Trials Information Desk
Scientific
Biogen Idec Research Limited
研究点 (21)
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