RK-4 Intracalvariosseous Injection in Treatment of Acute Large Hemispheric Infarction

NCT07166380 | Not Yet Recruiting Phase 1

• 1 other identifier: RK-4-LC-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

An open-label, blinded Ib/IIa study investigating the treatment of acute large hemispheric infarction by transcranial bone marrow injection of RK-4 injection For subjects with acute large hemispheric infarction who are contraindicated to vascular recanalization or have poor response to vascular recanalization therapy, the safety, tolerability, and PK characteristics of RK-4 injection injected into the brain cell marrow through the cranial bone marrow will be preliminarily evaluated, and the efficacy will be preliminarily explored. The main questions it aims to answer are:

• If drug RK-4 is safe and tolerate in the patients with LHI?
• What the pharmacokinetic profiles of RK-4 injection injected into the brain cell marrow through the cranial bone marrow?
• The efficacy of RK-4 injection injected into the brain cell marrow through the cranial bone marrow Researchers will analyze data from different groups, includes low dose group (1mg，QD), medium dose group(2mg，QD), high dose group(4mg，QD), to see If drug RK-4 is safe and tolerate in the patients with LHI and the pharmacokinetic profiles and efficacy of RK-4 injection injected into the brain cell marrow through the cranial bone marrow. Participants will:
• Take drug RK-4 (1 mg or 2 mg or 4 mg) by transcranial bone marrow injection once daily for consecutive 3 days.
• Truthfully provide medical history and "previous participation in clinical trials" and a statement of no history of mental disorders.
• Take the drug at the specified time every day according to the dosage prescribed by the doctor
• Receive the investigational drug as instructed by the doctor and visiting as required
• Tell the investigators about any medications (including chemicals, biological drugs, proprietary Chinese medicines, etc.) and related treatments you take during the study
• unpermitted stop the investigational drug yourself at the end of the study or when you decide to withdraw from the study, you need to stop the investigational drug as directed by your doctor to ensure your safety
• take reasonable contraception actions
• unallowed to use unmarketed drugs or other clinical trial drugs during the study

Conditions

Transcranial Bone Marrow Injection; RK-4; Acute Large Hemispheric Infarction; Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (10)

• Evaluate the safety of RK-4 in patients with LHI by incidence of subject getting abnormal results of physical examinations after treatment.

  Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Physical examinations will be conduct by the investigator through observation

  Day1 ~Day 14

• Evaluate the tolerability of RK-4 in patients with LHI by incidence of subject getting abnormal results of physical examinations after treatment.

  Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Physical examinations will be conduct by the investigator through observation

  Day1 ~Day 14

• Evaluate the safety of RK-4 in patients with LHI by incidence of subject getting abnormal results of vital signs after treatment.

  Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Vital signs(blood pressure, respiration, pulse, body temperature） will be assessed by according equipments.(electronic sphygmomanometer，thermometer).

  Day1 ~Day 14

• Evaluate the tolerability of RK-4 in patients with LHI by incidence of subject getting abnormal results of vital signs after treatment.

  Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Vital signs(blood pressure, respiration, pulse, body temperature） will be assessed by according equipments.(electronic sphygmomanometer，thermometer).

  Day1 ~Day 14

• Evaluate the safety of RK-4 in patients with LHI by incidence of subject getting abnormal results of 12-lead ECG after treatment.

  Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. 12-lead ECG will be analyzed by single RR Heart Rate, aggregate PR Interval, aggregate QRS Duration, aggregate RR Interval, aggregate QT Interval, aggregate QTC Interval. Normal range is provided by the site.

  Day1 ~Day 14

• Evaluate the tolerability of RK-4 in patients with LHI by incidence of subject getting abnormal results of 12-lead ECG after treatment.

  Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. 12-lead ECG will be analyzed by single RR Heart Rate, aggregate PR Interval, aggregate QRS Duration, aggregate RR Interval, aggregate QT Interval, aggregate QTC Interval. Normal range is provided by the site.

  Day1 ~Day 14

• Evaluate the safety of RK-4 in patients with LHI by incidence of subject getting abnormal results of laboratory tests after treatment.

  Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Laboratory tests are composed of hematology, urinalysis, serum chemistry, coagulation test. Normal range is provided by the site.

  Day1 ~Day 14

• Evaluate the tolerability of RK-4 in patients with LHI by incidence of subject getting abnormal results of laboratory tests after treatment.

  Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Laboratory tests are composed of hematology, urinalysis, serum chemistry, coagulation test. Normal range is provided by the site.

  Day1 ~Day 14

• Evaluate the safety of RK-4 in patients with LHI by rates of adverse events after treatment.

  An AE is defined as any untoward medical event that occurs after receiving a drug or treatment or any deterioration of a disease or symptom that existed before receiving the investigational product or treatment (excluding the disease studied in this trial) in a subject or a clinical investigation subject, whether or not considered related to the investigational product or treatment. Therefore, an AE can be a discomfort sign (including an abnormal laboratory finding), symptom, or transient disease beyond any indication, whether or not related to the investigational product or treatment. The investigator will name each AE reported during the study by MedDRA PT and evaluate their severity using the criteria of CTCAE 5.0. The relevance evaluation is divided into 5 grades: 1-certainly related; 2- probably/likely related; 3-possibly related; 4-unlikely related; 5 not related.

  Day1 ~Day 14

• Evaluate the tolerability of RK-4 in patients with LHI by rates of adverse events after treatment.

  An AE is defined as any untoward medical event that occurs after receiving a drug or treatment or any deterioration of a disease or symptom that existed before receiving the investigational product or treatment (excluding the disease studied in this trial) in a subject or a clinical investigation subject, whether or not considered related to the investigational product or treatment. Therefore, an AE can be a discomfort sign (including an abnormal laboratory finding), symptom, or transient disease beyond any indication, whether or not related to the investigational product or treatment. The investigator will name each AE reported during the study by MedDRA PT and evaluate their severity using the criteria of CTCAE 5.0. The relevance evaluation is divided into 5 grades: 1-certainly related; 2- probably/likely related; 3-possibly related; 4-unlikely related; 5 not related.

  Day1 ~Day 14

Secondary Outcomes (13)

• Evaluate the Cmax of single ascending doses of RK-4 in patients with LHI by venous blood and Phoenix WinNonlin

  Day1 ~Day 5

• Evaluate the AUC 0-t of single ascending doses of RK-4 in patients with LHI by venous blood and Phoenix WinNonlin.

  Day1 ~Day 5

• Evaluate the AUC 0-∞ of single ascending doses of RK-4 in patients with LHI by venous blood and Phoenix WinNonlin.

  Day1 ~Day 5

• Evaluate the Tmax of single ascending doses of RK-4 in patients with LHI by venous blood and Phoenix WinNonlin.

  Day1 ~Day 5

• Evaluate the t1/2 of single ascending doses of RK-4 in patients with LHI by venous blood and Phoenix WinNonlin.

  Day1 ~Day 5

Study Arms (1)

RK-4 injection

EXPERIMENTAL

patients will take drug RK-4 (1 mg or 2 mg or 4 mg) by transcranial bone marrow injection once daily for consecutive 3 days.

Drug: RK-4 injection

Interventions

RK-4 injection DRUG

patients with LHI will take drug RK-4 (1 mg or 2 mg or 4 mg) by transcranial bone marrow injection once daily for consecutive 3 days.

RK-4 injection

Eligibility Criteria

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

You may qualify if:

• ≤ age \< 81 years old, gender is not limited;
• The modified Rankin score (mRS) score ≤ 1 point before the onset of stroke;
• Administration can be completed within 24 hours after the onset of symptoms and signs of neurological deficit (for subjects with stroke after waking up or stroke without witnesses, the last normal time of symptom onset is the time of symptom onset);
• Clinical symptoms, signs and imaging diagnosed as cerebral infarction in the middle cerebral artery blood supply area, and the following characteristics are met:
• ≤NIHSS score ≤32 points, sum of the fifth upper limb and sixth lower limb scores≥6;
• Imaging suggests the core area of infarction: cerebral blood flow (CBF) in electronic computed scan perfusion imaging (CTP) \< 30% volume or apparent diffusion coefficient (ADC) value in magnetic resonance imaging (MRI) diffusion-weighted imaging (DWI) sequence \< 70-300ml of 620×10-6mm2/s lesion volume or ASPECTS score of 0-6 points. Priority is given to CTP test results. If both CTP and DWI are completed during the screening period and the examination results are inconsistent, the investigator needs to take all information (scanning time, imaging method for optimal response infarct size, etc.) into account and then make a reasonable judgment and record that; ASPECTS scores can be based on CTP or MRI, but CTP is preferred.
• If vascular reperfusion therapy is performed, the treatment is not effective and the following conditions are met:
• Extended thrombolytic grading (eTICI) = 2a;
• NIHSS score did not improve or progressed after vascular reperfusion treatment and the total score was still ≤ 32 points.
• Note: A decrease of 1 point or more is an improvement, and an increase of 1 point or more is progress.
• Subjects or their legal representatives voluntarily sign the informed consent form.

You may not qualify if:

• Those who meet one of the following items at screening cannot be enrolled:
• Concurrent cerebrovascular disease meets one of the following conditions:
• Combined with acute cerebral hemorrhage and subarachnoid hemorrhage;
• Combined with acute posterior circulation cerebral infarction, or severe posterior circulation vascular stenosis (\>70%);
• Imaging suggests bilateral involvement of the cerebral infarction area;
• The cause has been diagnosed by TOAST typing before screening, and other etiologies such as intracranial artery dissection, vasculitis, and moyamoya disease have been identified
• Hemorrhage transformation in the infarct area, the hematoma area ≥ 30% of the infarcted area, and has an obvious mass occupancy effect;
• Presence of clinical signs of cerebral herniation, e.g., unilateral or bilateral pupil dilation, fixation; Cerebral edema-related loss of consciousness (NIHSS 1a\>2 points), or other brainstem reflex loss judged by the investigator caused by cerebral edema or cerebral herniation formation; or other unstable signs of vital signs that are difficult to control;
• Planned cranial decompression flap decompression at screening;
• Refractory hypertension (systolic blood pressure \>200mmHg or diastolic blood \>110mmHg) or hypotension (systolic blood pressure \<70mmHg or diastolic blood pressure \<50mmHg) that is difficult to control with medication;
• Abnormal blood glucose (random venous blood glucose \< 2.8mmol/L or \>23mmol/L);
• Obvious abnormal liver function indicators or obvious abnormal renal function indicators; Note: Obvious abnormalities in liver function indicators refer to serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 times the upper limit of normal (ULN); Significant abnormal renal function measures are defined as eGFR less than 60 mL/min/1.73 m² (eGFR is calculated using the CKD-EPI formula).
• Acute ST-segment elevation myocardial infarction (MI), and/or acute decompensated heart failure (according to New York College of Cardiology (NYHA) cardiac function class III and IV) within the past 3 months\];
• Contraindications to transcranial bone marrow administration, such as skull fracture, skull infection, subdural/external hematoma, subscalp hematoma, scalp skin or subcutaneous infection, cranial plate obstruction in the past 3 months, etc.;
• Bleeding tendency that is not conducive to operation in the opinion of the investigator, including but not limited to: platelet count \<100×109/L, presence of coagulation dysfunction diseases such as hemophilia, etc.;

Sponsors & Collaborators

• Neurodawn Pharmaceutical Co., Ltd.: lead
• Fuzhou Neurodawn Rongkang Pharmaceutical Co., Ltd: collaborator

Study Sites (1)

Beijing TianTan Hospital

Beijing, Beijing Municipality, 100070, China

Location

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

yilong wang

CONTACT

13911666571; yilong528@aliyun.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2025
• First Posted: September 10, 2025
• Study Start: September 20, 2025
• Primary Completion: February 20, 2026
• Study Completion (Estimated): May 19, 2026
• Last Updated: September 30, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)