A Study of ASP2246 for People Who Have Movement Problems Caused by Brain Injury After a Stroke

Inclusion Criteria: * Participant should have had an ischemic cerebral infarction at least 3 months, but not more than 12 months, before signing informed consent. This stroke must be the first-ever stroke for the participant. * Participant has current neuromotor dysfunction with a modified Rankin Scale (mRS) score between 2 to 4 at screening. * Participant has Fugl-Meyer Assessment (FMA)- upper extremity (UE) score ≥ 20 to ≤ 50 and FMA-lower extremity (LE) score \< 21 at screening. * Participant has supratentorial perforator area infarction (single lacunar infarction or branch-atheromatous disease \[BAD\]), as assessed clinically and by magnetic resonance imaging (MRI) at screening. * Participant has completed recovery phase rehabilitation after cerebral infarction and spontaneous improvement is not expected during the study period. * Participant is willing and physically able to participate in the designated rehabilitation therapy during the study period. * Female participant is not pregnant and at least 1 of the following conditions apply: * Not a woma(e)n of childbearing potential (WOCBP) * WOCBP who has a negative urine or serum pregnancy test at screening (Unique to Japan: with a medical interview) and agrees to follow contraceptive guidance from the time of giving informed consent to at least 180 days after surgery. * Female participant must not be breastfeeding or lactating starting at screening and for 180 days after surgery. * Female participant must not donate ova after undergoing surgery and for 180 days after surgery. * Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) for a minimum of 180 days after surgery. * Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for a minimum of 180 days after surgery. * Male participant must not donate sperm for a minimum of 180 days after surgery. * Participant agrees not to participate in another interventional study (including rehabilitation) while receiving study intervention/participating for up to 52 weeks in the present study. * Participant agrees that the use of antiplatelet, oral anticoagulant or nonsteroidal anti-inflammatory drugs (NSAIDs) will be determined by the local medical staff in accordance with the American College of Chest Physicians Clinical Pharmacy 2022 Guidelines and the Japanese Guidelines for the Management of Stroke 2021. The Japanese guidelines specify that no antiplatelet, oral anticoagulant or NSAIDs are to be restarted post-surgery until results of the day 1 head MRI or computerized tomography (CT) are reviewed and restarting medication is deemed safe. Exclusion Criteria: * Participant has a cerebral infarct volume \> 3.4 cm\^3 or \< 0.37 cm\^3, as measured by MRI (use of either a central or local reading is acceptable). * Participant has a primary intracerebral or intracranial hemorrhage. * Participant has a history of central nervous system (CNS) malignancy or a known presence of any malignancy, unless in remission for \> 5 years. Exception: The participant with basal or squamous cell skin cancer that has been successfully treated will be considered eligible even if they have been in remission for \< 5 years. * Participant had motor dysfunction of mRS \> 2 before the onset of the stroke (premorbid mRS). * Participant has a history of seizures. * Participant has apparent contractures impeding joint movement at shoulder, elbow, forearm, wrist, hand, hip, knee or ankle. * Participant with spasticity of grade 2 or higher on the modified Ashworth Scale. * Participant has any other neurologic, neuromuscular or orthopedic disease that limits motor function. * Participant has an active infection. * Participant has a history of or current diagnosis of immunodeficiency. * Participant has been deemed to have a high risk of recurrent stroke during the study period (e.g., a family history strongly suggestive of hereditary cerebrovascular disease, such as moyamoya disease and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). * Participant has an uncontrolled systemic illness, including, but not limited to, hypertension (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 95 mmHg), resistant hypertension (systolic blood pressure \[BP\] ≥ 140 mmHg or diastolic BP ≥ 90 mmHg in a participant who is taking 3 or more medications for hypertension), bleeding disorders, hypercoagulability, diabetes, renal, hepatic or cardiac failure, morbid obesity, or uncontrolled sleep apnea. * Participant has any positive findings on tests for occult malignancy, unless a nonmalignant etiology is confirmed. * Participant has an uncontrolled major psychiatric illness, including depression (Hamilton Score of \> 14). * Participant has a presence of craniectomy (without bone flap replacement) or other contraindication for stereotactic surgery. * Participant has signs and symptoms of intracranial herniation or increased intracranial pressure. * Participant with a history of, or electrocardiogram (ECG) evidence suggestive of, recent myocardial infarction (within 6 months of surgery), major dysrhythmia, atrial fibrillation or congestive heart failure. * Participant has a substance-related and addictive disorders as defined by the Diagnostic and Statistical Manual of Mental Disorders-5 criteria, including drug or alcohol use. * Participant has contraindications to MRI or MRI contrast agent(s). * Participant has Montreal Cognitive Assessment (MoCA) score \< 26. * Participant has a history of suicide attempt(s), suicidal behavior, or suicidal ideation (indicated by a 'yes' response to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale \[C-SSRS\]) within 12 months prior to study enrollment, or who is assessed at screening to be at a significant risk of committing suicide. * Participant has a history of using warfarin or direct oral anticoagulant (DOAC). Exception: The participant will be considered eligible if the medication was discontinued at least 6 months prior to study enrollment, and the embolic source has resolved without recurrence. * Participant has a history of neuroleptic drug use. Exception: The participant will be considered eligible if they are neuroleptic medication-free for at least 6 months and their psychiatric symptoms remain mild, stable and do not meet the exclusion criteria. * Participant has a history of antiepileptic drug use for seizures. Note: For the participant who has used or is using antiepileptic medications for conditions other than seizures, a detailed risk assessment needs to be conducted to determine eligibility. * Participant has had botulinum toxin injection, phenol injection, intrathecal baclofen, or any other interventional treatments for spasticity (except bracing and splinting) within the previous 3 months. * Participant has present or previous history of participation in a study with ASP2246. * Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening. * Participant has inadequate organ function as indicated by the laboratory values at screening. * Participant has any condition that makes the participant unsuitable for study participation. * Participant has known or suspected hypersensitivity to ASP2246 or any components of the formulation used.