Neutropenia and Fever
Conditions
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.
Interventions
DRUGAmphotericin B liposomes
Amphotericin B liposomes for injection, 3 mg/kg, qd, IV
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall success rate | From the initiation of the third dose to 7 days after the last dose | A successful outcome is defined as fulfilling all components of a prespecified 5-part composite endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients survived from the initiation of the first dose to 7 days after the last dose | From the initiation of the third dose to 7 days after the last dose | Percentage of patients survived |
| Percentage of patients without discontinuation of study drug due to side effects or lack of efficacy during the treatment period | From the initiation of the third dose to 7 days after the last dose | Percentage of patients without discontinuation of study drug due to side effects or lack of efficacy |
| Percentage of patients experienced fever reduction during neutropenia after initiation of treatment | From the initiation of the third dose to 7 days after the last dose | Percentage of patients experienced fever reduction during neutropenia |
| Percentage of patients without new fungal infections from the initiation of the first dose to 7 days after the last dose | From the initiation of the third dose to 7 days after the last dose | Percentage of patients without new fungal infections |
| Adverse events | From the screening period to 14 days after the last dose | Adverse events |
| Pharmacokinetic profile of amphotericin B | Pre-dose and multiple timepoints up to 4 hours of the last dose | Pharmacokinetic profile of amphotericin B, Such as Peak Plasma Concentration (Cmax) |
| Percentage of patients with complete or partial remission of confirmed or clinically diagnosed IFD (baseline fungal infection) at the end of treatment | From the initiation of the third dose to 7 days after the last dose | Percentage of patients with complete or partial remission of confirmed or clinically diagnosed Invasive fungal disease (baseline fungal infection) |
Contacts
Primary ContactXuefang Xia
Outcome results
None listed