A Phase 2b, Prospective, Randomized, Multi-Center, Double-Blinded, Controlled Trial to Assess the Efficacy and Safety of Stereotactic Intracerebral Transplantation of Allogeneic Neural Stem Cells CC-101 (f/k/a NR1) in Adults With Chronic Ischemic Subcortical ± Cortical Stroke
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 36
- 主要终点
- Total Fugl-Meyer Motor Scale (FMMS) Score on Day +365 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.
研究概览
简要总结
The suNR1se II Study is a Phase 2b randomized, controlled, multi-center clinical trial evaluating the efficacy and safety of stereotactic intracerebral administration of CC-101 (f/k/a NR1), an investigational allogeneic neural stem cell therapy, in adults with chronic ischemic stroke and persistent motor impairment. The study is designed to assess whether administration of CC-101 immediately adjacent to the region of prior stroke injury may improve motor function recovery compared with a sham surgical control procedure. The study will also evaluate the role of short-term anti-rejection therapy with tacrolimus in subjects receiving CC-101. Approximately 36 participants will be randomized in a 1:1:1 ration to receive CC-101 plus tacrolimus, sham surgery (no CC-101) plus tacrolimus-matched placebo, or CC-101 plus tacrolimus-matched placebo. Participants will be followed for safety and functional outcomes for at least 12 months following the study procedure.
详细描述
CC-101 (f/k/a NR1) is an investigational allogeneic neural stem cell therapy being developed to support endogenous repair and regenerative mechanisms within the brain following ischemic injury and infarction (i.e., ischemic stroke). Rather than directly replacing stroke-damaged and dead brain cells and tissue, CC-101 is intended to promote recovery through local production of biologically active factors that support neurogenesis (i.e., new brain cell production), angiogenesis (i.e., new blood vessel formation), plasticity (i.e., rewiring of synaptic connections), extracellular matrix remodeling (i.e., change materials around brain cells), and modulation of inflammation. The suNR1se II Study is a prospective, randomized, controlled Phase 2b study designed to evaluate the efficacy and safety of stereotactic intracerebral administration of CC-101 in adults with chronic ischemic subcortical ischemic stroke, with or without adjacent cortical involvement. Participants will be randomized equally to one of three study arms: 1) CC-101 plus tacrolimus (Experimental Arm A), 2) sham surgery plus placebo (Control Arm B), or 3) CC-101 plus placebo (Exploratory Arm C). The inclusion of sham surgery control (Arm B) and tacrolimus-matched placebo anti-rejection therapy (Arms B & C) is intended to support rigorous evaluation of CC-101 treatment effect and further characterization of the role of tacrolimus in allogeneic neural stem cell therapy for chronic ischemic stroke. The primary efficacy assessment will evaluate changes in arm and leg motor functions between baseline and 12 months following intervention. Safety assessments will include adverse events, serious adverse events, neurosurgical complications, imaging findings, laboratory assessments, hospitalization events, and mortality.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants; non-neurosurgeon investigators; study staff responsible for safety assessments; outcome raters; Sponsor personnel involved in study conduct, data review, and study management; and other Sponsor representatives with responsibility for trial oversight will remain blinded to treatment assignment throughout the study. Neurosurgical personnel performing the study procedures and other designated personnel with responsibilities requiring knowledge of treatment assignment (e.g., preparation and administration of investigational product) will be unblinded. Procedures will be implemented to maintain the blind.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of completed ischemic subcortical stroke in the middle cerebral artery (MCA) distribution with or without cortical involvement based on magnetic resonance imaging (MRI) and/or computed tomography (CT) scan(s).
- •Index stroke occurred ≥ 6 months and ≤ 84 months prior to providing informed consent.
- •Age ≥ 18 years and ≤ 75 years at the time of providing informed consent.
- •Chronic motor neurological deficit due to the index stroke.
- •Total Fugl-Meyer Motor Scale (FMMS) > 25 and ≤ 75 at baseline.
- •Modified Rankin Score (mRS) of 2-4 at baseline.
- •Subjects taking oral anti-spasticity agent (such as tizanidine hydrochloride or baclofen) must be on a stable dose for 90 days prior to a Screening/Baseline visit.
排除标准
- •Stroke lesion <1 cm3 or >100 cm3 as measured by MRI.
- •Previous history of symptomatic stroke(s) with incomplete motor recovery (NOT including index stroke).
- •Complete or near complete lack of right and/or left upper extremity and/or right and/or left lower extremity movement as defined by the MRC Scale for Muscle Strength scores.
- •History of any neuromuscular, rheumatologic, autoimmune, orthopedic, or other disease or condition that limits motor function.
- •Acute myocardial infarction (heart attack), acute pulmonary embolism (blood clot to the lungs), acute proximal deep vein thrombosis (blood clot in the leg or arm), acute peripheral arterial occlusion, or any other type of acute blood clotting episode within six (6) months of study screening.
- •Intracoronary and/or other intra-arterial stent placement within 12 months of study Screening/Baseline visits requiring uninterrupted anticoagulant and/or anti-platelet therapy.
- •Contracture involving a shoulder, elbow, wrist, finger, hip, knee, and/or ankle.
- •Any contraindication to stereotactic brain surgery.
- •Presence of serum anti-Human Leukocyte Antigen (HLA) Class I and/or Class II antibodies to donor NR1 cells with a Luminex assay value greater than the larger of the central lab's reference ULN or 3,000 Maximum Fluorescence Intensity.
结局指标
主要结局
Total Fugl-Meyer Motor Scale (FMMS) Score on Day +365 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.
时间窗: Baseline to Day +365.
The total Fugl-Meyer Motor Scale (FMMS) score (0-100; the larger the better) reflects the sum of the upper extremity (0-66) and lower extremity (0-34) FMMS scores. For each study subject, this clinical assessment of motor function on Day +365 will be compared with the baseline total FMMS score to determine the interval change in motor function.
次要结局
- Total Fugl-Meyer Motor Scale (FMMS) Score on Day +365 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.(Baseline to Day +365.)
- Total Fugl-Meyer Motor Scale (FMMS) Score on Day +90 and Day +182 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.(Baseline to Day +90 and baseline to Day +182)
- Total Fugl-Meyer Motor Scale (FMMS) Score on Day +90 and Day +182 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.(Baseline to Day +90 and baseline to Day +182.)
- Upper Extremity Motor Function as Assessed by the Action Research Arm Test (ARAT) on Day +365 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.(Baseline to Day +365.)
- Barthel Index on Day +90 and Day +182 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.(Baseline to Day +90 and baseline to Day +182.)
- Gait Velocity Using the Comfortable Gait Speed Test Measuring 10 Meters of Timed Gait Speed on Day +365 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0..(Baseline to Day +365.)
- Overall Survival on Day +90, Day +182, and Day +365 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.(Survival rates at Day +90, Day +182, and Day +365.)