CC-101 (f/k/a NR1) Neural Stem Cell Transplantation for Adults With Chronic Ischemic Stroke

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.

KEY INCLUSION CRITERIA:

• 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.

KEY EXCLUSION CRITERIA:

• 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.