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

NCT07318714 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2246-CL-0101jRCT2033250653
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

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. After this, they will have physical therapy and continue to have safety checks for about 1 year after their brain surgery.

Conditions

Chronic Ischemic Stroke

Keywords

Safety; Tolerability; Efficacy; ASP2246

Outcome Measures

Primary Outcomes (5)

• Number of participants with Dose-Limiting Toxicity (DLT)

  A DLT will be defined as an Adverse Event (AE) ≥ 3 Grade that is attributed to study intervention or surgical procedure. This determination will be based on the investigator's initial assessment of causality and will be confirmed by the Dose Escalation and Safety Committee (DESC). A Grade 3 AE is defined as a severe or medically significant event that is not immediately life-threatening, but may cause hospitalization or prolongation of hospitalization, be disabling, or limit a patient's ability to perform self-care activities of daily living (ADL).

  Up to 2 Weeks

• Number of participants with Treatment-Emergent Adverse Events (TEAEs)

  An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures. A TEAE is defined as an AE observed until 52 weeks after surgery on day 1.

  Up to 52 Weeks

• Number of participants with Serious Adverse Events (SAEs)

  A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other situations.

  Up to 52 Weeks

• Number of participants with an Adverse Event of Special Interest (AESI)

  An AESI includes intracranial hemorrhage, cerebral edema (local or extensive), meningitis/encephalitis/encephalopathy (infectious or aseptic), seizures, worsening or new onset of neurologic deficits, intracranial malignancies/tumor formation, and immunogenic reactions.

  Up to 52 Weeks

• Number of Participants with Suicidal Ideation and/or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)

  The C-SSRS is a validated, clinician-administered tool used to assess suicidal ideation and behavior. Number of participants that have an affirmative response provided to the 5 items for suicidal ideation (1. Wish to be dead, 2. Non-specific active suicidal thoughts, 3. Active suicidal ideation with any methods (not plan) without intent to act, 4. Active suicidal ideation with some intent to act, without specific plan, 5. Active suicidal ideation with specific plan and intent) and/or to the 5 items for suicidal behavior (1. Preparatory acts or behavior, 2. Aborted attempt, 3. Interrupted attempt, 4. Actual attempt, 5. Completed suicide) will be reported.

  Up to 52 Weeks

Secondary Outcomes (15)

• Pharmacokinetics (PK) of ASP2246 in whole blood: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)

  Up to 52 Weeks

• PK of ASP2246 in whole blood: AUC from the time of dosing up to the time of the last measurable concentration (AUClast)

  Up to 52 Weeks

• PK of ASP2246 in whole blood: maximum concentration (Cmax)

  Up to 52 Weeks

• PK of ASP2246 in plasma: AUCinf

  Up to 52 Weeks

• PK of ASP2246 in plasma: AUClast

  Up to 52 Weeks

Study Arms (3)

ASP2246 Dose Escalation (Part 1)

EXPERIMENTAL

Participants will undergo stereotactic brain surgery and receive sequential dose levels of a single intracerebral parenchymal infusion of ASP2246. Participants will undergo rehabilitation therapy.

Drug: ASP2246; Procedure: Brain surgery; Other: Rehabilitation therapy

ASP2246 Dose Expansion (Part 2)

EXPERIMENTAL

Participants will undergo stereotactic brain surgery and receive a single intracerebral parenchymal infusion of ASP2246. The dosage will be selected from Dose Escalation (Part 1). Participants will undergo rehabilitation therapy.

Drug: ASP2246; Procedure: Brain surgery; Other: Rehabilitation therapy

Sham Dose Expansion (Part 2)

SHAM COMPARATOR

Participants will undergo a sham surgery and rehabilitation therapy.

Procedure: Sham surgery; Other: Rehabilitation therapy

Interventions

ASP2246 DRUG

Intracerebral parenchymal infusion via SmartFlow Neuro cannula.

ASP2246 Dose Escalation (Part 1); ASP2246 Dose Expansion (Part 2)

Brain surgery PROCEDURE

Stereotactic brain surgery

ASP2246 Dose Escalation (Part 1); ASP2246 Dose Expansion (Part 2)

Sham surgery PROCEDURE

Sham surgery without the dura incised.

Sham Dose Expansion (Part 2)

Rehabilitation therapy OTHER

Rehabilitation 3 days per week for up to 12 weeks.

ASP2246 Dose Escalation (Part 1); ASP2246 Dose Expansion (Part 2); Sham Dose Expansion (Part 2)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Inc: lead

Study Sites (1)

Toyama University Hospital

Toyama, Toyama, Japan

RECRUITING

MeSH Terms

Interventions

Rehabilitation

Intervention Hierarchy (Ancestors)

Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Associate Medical Director

  Astellas Pharma Inc

  STUDY DIRECTOR

Central Study Contacts

Astellas Pharma Inc.

CONTACT

+81-3-3244-6500; Astellas.registration@astellas.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2026
• First Posted: January 6, 2026
• Study Start: April 3, 2026
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): February 28, 2030
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

JP (1)