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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
36
Investigational allogeneic neural stem cell product administered stereotactically via intracerebral injection immediately adjacent to the prior stroke lesion.
Oral tacrolimus or tacrolimus-matched placebo initiated prior to study intervention and continued for approximately 60 days following study intervention per protocol-defined dosing and taper schedule.
Participants will undergo a partial thickness burr hole craniotomy without disruption of the meninges or transplantation of any cells as a means to maintain treatment masking.
Total Fugl-Meyer Motor Scale (FMMS) Score on Day +365 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.
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.
Time frame: Baseline to Day +365.
Total Fugl-Meyer Motor Scale (FMMS) Score on Day +365 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.
Each study subject will be categorized as having an increase in total FMMS score of ≥10 points or an increase of \<10 points (including unchanged scores and decreased scores) between baseline assessment and assessment on Day +365 following neurosurgical intervention.
Time frame: 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.
For each study subject, this clinical assessment of motor function on Day +90 and Day +182 will be compared with the baseline total FMMS score to determine the interval change in motor function.
Time frame: 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.
Each study subject will be categorized as having an increase in total FMMS score of ≥10 points or an increase of \<10 points (including unchanged scores and decreased scores) between baseline assessment and assessments on Day +90 and on Day +182 following neurosurgical intervention.
Time frame: 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.
Each study subject will be categorized as having an increase in ARAT score of ≥5.7 points or an increase of \<5.7 points (including unchanged scores and decreased scores) between baseline assessment and assessment on Day +365 following neurosurgical intervention.
Time frame: Baseline to Day +365.
Barthel Index on Day +90 and Day +182 Following Neurosurgical Intervention (CC-101 transplantation or sham surgery) on Day 0.
For each study subject, this clinical assessment of functional independence on Day +90 and Day +182 will be compared with the baseline Barthel Index to determine the interval change.
Time frame: 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..
Each study subject will be categorized as having or not having an improvement in gait function by at least one functional level using the 10-meter walk test between baseline assessment and assessment on Day +365 following neurosurgical intervention.
Time frame: 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.
Subject survival to key assessment milestones will be assessed. Time to all-cause subject death following study Day 0 neurosurgery will be estimated using the product-limit (Kaplan-Meier) method.
Time frame: Survival rates at Day +90, Day +182, and Day +365.
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