Single center, open-label Phase-IIa trial of tocilizumab in patients with sepsis or septic shock

JRCT ID: jRCT2051230173

Registered date:26/01/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Sepsis or Septic shock
• Date of first enrollment: 15/02/2024
• Target sample size: 60
• Study type: Interventional
• Intervention(s): Tocilizumab 8 mg/kg (maximum dose 800 mg) is administered as a single intravenous infusion. If symptoms do not improve within 24 hours after the first dose of tocilizumab base on clinical tests (CRP, etc.) and the patient's condition, one additional infusion of up to 8 mg/kg(maximum dose 800 mg) of tocilizumab can be given at least 8 hours after the end of the first dose.

Outcome(s)

Primary Outcome

(1) Pharmacodynamics
Blood biomarkers: IL-6, sIL-6R, CRP
Correlation between blood biomarkers and serum tocilizumab concentration
(2) Safety
Incidence and severity of adverse events
Percentage of subjects who developed secondary infections
Change from baseline in laboratory values by time point
Vital signs
Change from baseline in chest X-ray/CT scan

• Secondary Outcome: Pharmacokinetics:Serum tocilizumab concentration

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: < 85age old
• Gender: Both

Include criteria

1) Patients who have obtained consent for participation in the clinical trial from the patient or the patient's surrogate through the consent document
2) Japanese patients who are at least 18 years old and less than 85 years old at the time of consent
3) Patients diagnosed with sepsis or septic shock based on Sepsis-3
4) Patients with infection or suspected infection in the lungs, abdomen, urinary tract, etc.
5) Patients with acute organ failure within 48 hours of ICU admission
6) Patients with lactate levels greater than 2 mmol/L (18 mg/dL) at screening
7) Patients with blood IL-6 level of higher than or equal to 100 pg/mL at screening

Exclude criteria

1) Patients who are judged by the investigator (subinvestigator) to die within 48 hours with or without treatment.
2) Patients with organic brain disorder.
3) Patients with cardiopulmonary arrest before admission to the ICU.
4) Patients chronically receiving dialysis.
5) Patients with uncontrolled coagulopathy requiring blood transfusion or with active bleeding.
6) Patients with shock for reasons other than sepsis.
7) Patients requiring surgical drainage. However, catheter drainage is acceptable.
8) Patients with no intention to prolong life or resuscitation.
9) Patients who have suffered serious trauma or burns within 36 hours prior to ICU admission.
10) Patients with soft tissue skin infections.
11) Patients who require laparotomy during the study period or who have undergone laparotomy,craniotomy,or thoracotomy within 24 hours prior to ICU admission.
12) Patients with active carcinoma requiring active treatment such as surgery,radiotherapy,or anticancer therapy.
13) Patients with a history of severe allergic reaction to tocilizumab or other monoclonal antibodies.
14)Patients with active tuberculosis infection at the time of enrollment.
15) Patients with chronic hepatitis B or C at the time of enrollment.
16) Patients who have received drug therapy (oral or immunomodulatory) for rejection in the 3 months prior to enrollment.
17) Patients who received anti-IL-6 therapy (including tocilizumab) in the 3 months prior to enrollment.
18) Patients with ALT or AST greater than 10 times the upper reference limit at screening.
19) Patients with hepatic encephalopathy.
20) Patients who meet the following laboratory criteria at screening.
Platelet count < 5 x10^4 /uL
White blood cell count less than 3500/uL
Neutrophil count less than 1000/uL
21) Patients with COVID-19 infection.
22) Patients who have been previously enrolled in this study and have received an investigational drug.
23) Pregnant or lactating women, or women of childbearing potential with a positive pregnancy test on screening.
24) Patients who have received a live vaccine or attenuated live vaccine within 4 weeks prior to screening.
25) Patients who received any other investigational drug within 30 days prior to enrollment or within 5 times the half-life of the other investigational drug, whichever is longer.
26) Patients who are judged by the investigator (subinvestigator) to be incompetent to comply with the study protocol.
27) Patients who are judged by the investigator to be incapable of abstinence or contraception for a certain period of time. In addition, male patients who are judged by the investigator to be unable to abstain from sperm donation during the same period.
28) Patients who are judged by the investigator or subinvestigator to be unsuitable for participation in the clinical trial for any reason.

Related Information

• Primary Sponsor: Jun Oda