A Study of Amphotericin B Liposome for Injection in Patients With Persistent Neutropenia and Fever

Phase 3

• Conditions: Neutropenia and Fever
• Interventions: Drug: Amphotericin B liposomes

• Registration Number: NCT05108545
• Lead Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

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.

Study Timeline

• Status Verified: 2021-09
• Study First Submitted: 2021-09-30
• Study First Submitted QC: 2021-11-01
• Last Update Submitted: 2021-11-01
• Study First Posted: 2021-11-05
• Last Update Posted: 2021-11-05
• Study Start: 2021-12-15
• Primary Completion: 2022-07-31
• Study Completion: 2023-01-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 93

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Amphotericin B liposomes	Amphotericin B liposomes	Patients with suspected fungal neutropenia and fever will receive amphotericin B liposome 3 mg/kg intravenously. Treatment will be continued until the ANC≥500 /mm\^3 (0.5×10\^9 /L) for more than 72 hrs in terms of patients without evidence of baseline fungal infection and breakthrough fungal infection; or treatment will be continued according to investigator's judgement with a duration ranging from 14 days to 12 weeks in terms of patients with evidence of baseline fungal infection and breakthrough fungal infection.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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 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)
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
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
Adverse events	From the screening period to 14 days after the last dose	Adverse events
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
Pharmacokinetic profile of amphotericin B	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)"