This study is for adults who have difficulty moving a few months after a stroke. In this study, ASP2246 will be given to people for the first time. This is known as a "first in human" study.
The main aims of the study are to check the safety of ASP2246, how well people tolerate it, and to find suitable doses of ASP2246 to use later in this study and in future studies.
This study has 2 parts. In Part 1, people will have brain surgery. During the surgery, different small groups of people will receive a lower to a higher dose of ASP2246. Each dose will be given slowly through a special tube to the damaged part of the brain (intracerebral parenchymal infusion). Any medical problems will be recorded at each dose. This is done to find suitable doses to use in Part 2 of the study.
In Part 2, other different groups of people will undergo the same type of brain surgery. Some people will receive a higher dose of ASP2246, and some people will receive a lower dose of ASP2246. These are the doses from Part 1. Also, another group of people won't be given ASP2246 during brain surgery. This is known as a sham procedure. This is done so neither the people taking part in Part 2, nor the study doctors (apart from the surgeons) know who will be given ASP2246.
After brain surgery, people will be observed for about 2 weeks. For people in Part 1, this will take place in the hospital. For people in Part 2, the observation in hospital may be longer or shorter, depending on the results from Part 1. People in both Parts 1 and 2 will have physical therapy for 12 weeks after surgery and continue to have safety checks for about 1 year after their brain surgery.
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 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).