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
18≤ 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);
16≤NIHSS score ≤32 points, sum of the fifth upper limb and sixth lower limb scores≥6;
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
Sequential
RK-4 injection
Drugpatients 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.
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
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
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).
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).
Evaluate the Cmax of single ascending doses of RK-4 in patients with LHI by venous blood and Phoenix WinNonlin
Maximum observed plasma concentration. It was obtained directly from the measured plasma concentration-time data.
Evaluate the AUC 0-t of single ascending doses of RK-4 in patients with LHI by venous blood and Phoenix WinNonlin.
Area under the concentration-time curve from time 0 to the time of the last quantifiable concentration. Calculated according to linearity trapezoidal rule: AUC (i, i+1) = (Ti+1-Ti) (Ci+Ci+1) /2, and AUC0-t is the sum of all AUC (i, i + 1)
Evaluate the AUC 0-∞ of single ascending doses of RK-4 in patients with LHI by venous blood and Phoenix WinNonlin.
Area under the concentration-time curve from time 0 to infinity (extrapolated). AUC 0-∞ =AUC 0-t + Ct/λz (Ct is the last measured plasma concentration).
Evaluate the Tmax of single ascending doses of RK-4 in patients with LHI by venous blood and Phoenix WinNonlin.
Time to reach maximum observed plasma concentration. It was obtained directly from the measured plasma concentration-time data.
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Neurodawn Pharmaceutical Co., Ltd.
Lead sponsor
Fuzhou Neurodawn Rongkang Pharmaceutical Co., Ltd
Collaborator
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