Clinical trial NCT05108545: A Study of Amphotericin B Liposome for Injection in Patients With Persistent Neutropenia and Fever
Official title: A Multicenter, Open-label, Phase Ⅲ Study to Evaluate the Efficacy and Safety of Amphotericin B Liposome for Injection in Patients With Persistent Febrile Neutropenia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Neutropenia and Fever
Lead sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-11-05
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, single-arm, phase III study to evaluate the safety and efficacy of Amphotericin B liposomes in patients with persistent neutropenia and fever.

Detailed description: This is a multicenter, open-label, single-arm, phase III study to evaluate the safety and efficacy of Amphotericin B liposomes in patients with persistent neutropenia and fever. About 93 patients will be recruited in this study. The patients will receive Amphotericin B liposomes intravenous infusion at a dose of 3 mg/kg over 2 hours once daily (qd) for a maximum of 12 weeks.

Eligibility criteria: Inclusion Criteria:

1. Aged 18 \~ 75 years (inclusive), no gender limitation.
2. Patients with neutrophilic deficiency after solid tumor chemotherapy, hematological tumor chemotherapy, hematopoietic stem cell transplantation, etc. (absolute neutrophil count (ANC) in peripheral blood \<500 /mm\^3 (0.5×10\^9 /L) for at least 72 hours at screening).
3. Persistent or recurrent fever (oral temperature ≥38℃ or axillary temperature ≥37.7℃ within 24 hours prior to randomization) after at least 72 hours on broad-spectrum antibiotics, and considering fever to be associated with suspected fungal infection.
4. Female patients must meet one of the following conditions:

   1. Menopausal patients, menopause at least 1 year;
   2. Patients of childbearing age: Negative for blood/urine pregnancy test before enrollment; agree to take a guaranteed, effective contraception during the study and within 4 weeks after the study.
5. Male patients and their partners must use effective contraception throughout the study period and up to 4 weeks after leaving the study.
6. Patients fully understand and voluntarily participate in this study and sign informed consent.

Exclusion Criteria:

1. History of allergy to liposomes or amphotericin B.
2. Received systemic treatment of amphotericin B or amphotericin B-containing formulation within 10 days prior to enrollment.
3. Liposome used within 1 month before the signing informed consent.
4. Confirmed or clinically diagnosed invasive fungal infection or known uncontrolled bacteremia or sepsis at screening.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≥3;
6. Abnormal liver function, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≥5 × the upper limit of normal (ULN), or ALT/AST ≥3 × ULN with total bilirubin ≥1.5 × ULN, or total bilirubin ≥3 × ULN.
7. Serum creatinine \> 2 × ULN.
8. Serum potassium concentration ≤3.0 mmol/L prior to the first administration, or serum potassium concentration ≤the lower limit of normal value (LLN) in patients undergoing digitalization.
9. 12-lead ECG presenting II or III degree atrioventricular block, long QT syndrome or corrected QT interval\>480 ms in the absence of a pacemaker.
10. Cardiac function grade III/IV (NYHA).
11. Tachyarrhythmia requiring intervention and a history of high-risk coronary heart disease such as unstable angina and acute coronary syndrome.
12. Human immunodeficiency virus (HIV) antibody or treponema pallidum specific antibody (TPHA) positive; active tuberculosis on CT of chest (to be determined by investigator).
13. Pregnant or lactating female.
14. A history of drug abuse (non-medical use of narcotic drugs or psychotropic substances) or drug dependence (narcotics, stimulants and psychotropic substances, etc.) within 2 years.
15. Plan to use prohibited drugs during the study period.
16. Enrolled in any other clinical trials of drugs or medical devices within 3 months prior to screening.
17. Life expectancy \< 2 months;
18. Not suitable for this study as decided by the investigator due to other reasons

Primary outcomes:
measure: Overall success rate
timeFrame: From the initiation of the third dose to 7 days after the last dose
Secondary outcomes:
measure: Percentage of patients without new fungal infections from the initiation of the first dose to 7 days after the last dose
timeFrame: From the initiation of the third dose to 7 days after the last dose
measure: Percentage of patients survived from the initiation of the first dose to 7 days after the last dose
timeFrame: From the initiation of the third dose to 7 days after the last dose
measure: Percentage of patients without discontinuation of study drug due to side effects or lack of efficacy during the treatment period
timeFrame: From the initiation of the third dose to 7 days after the last dose
measure: Percentage of patients experienced fever reduction during neutropenia after initiation of treatment
timeFrame: From the initiation of the third dose to 7 days after the last dose
measure: Percentage of patients with complete or partial remission of confirmed or clinically diagnosed IFD (baseline fungal infection) at the end of treatment
timeFrame: From the initiation of the third dose to 7 days after the last dose
measure: Adverse events
timeFrame: From the screening period to 14 days after the last dose
measure: Pharmacokinetic profile of amphotericin B
timeFrame: Pre-dose and multiple timepoints up to 4 hours of the last dose
measure: Pharmacokinetic profile of amphotericin B
timeFrame: Pre-dose and multiple timepoints up to 4 hours of the last dosePharmacokinetic profile of amphotericin B, Such as "Area under the plasma concentration versus time curve (AUC)"
Other outcomes:
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