A Study of ABCD for Injection in Subjects With Invasive Candidiasis and Invasive Aspergillus

NCT05707832 | Completed Phase 3

• 1 other identifier: HF114-006
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, open-label, non-controlled, single-arm clinical trial to evaluate the safety, efficacy and population pharmacokinetics of Amphotericin B cholesteryl Sulfate Complex for Injection domestic formulations (ABCD) in the treatment of confirmed invasive candidiasis (IC) and confirmed/clinically diagnosed invasive aspergillus (IA) disease.

Conditions

Invasive Candidiasis; Invasive Aspergillosis

Outcome Measures

Primary Outcomes (4)

• The number and percentage of subjects whose treatment is terminated due to study abnormal laboratory tests leads to drug related adverse events.

  The number and percentage of subjects whose treatment is terminated due to study abnormal laboratory tests leads to drug related adverse events.

  From Day 1 to the end of treatment, no more than 6 weeks.

• The number and percentage of subjects whose treatment is terminated due to study the infusion reaction leads to drug related adverse events.

  The number and percentage of subjects whose treatment is terminated due to study the infusion reaction leads to drug related adverse events.

  From Day 1 to the end of treatment, no more than 6 weeks.

• The number and percentage of subjects with study the infusion reaction leads to drug related adverse events.

  The number and percentage of subjects with study the infusion reaction leads to drug related adverse events.

  From Day 1 to the end of treatment, no more than 8 weeks.

• The number and percentage of subjects with study abnormal laboratory tests leads to drug related adverse events.

  The number and percentage of subjects with study abnormal laboratory tests leads to drug related adverse events.

  From Day 1 to the end of treatment, no more than 8 weeks.

Secondary Outcomes (5)

• Population pharmacokinetic characteristics (PPK analysis)

  From Day 1 to the end of treatment, no more than 8 weeks.

• The proportion of subjects who are generally effective

  From Day 1 to the end of treatment, no more than 44 days.

• Percentage of subjects that are microbiologically valid

  From Day 1 to the end of treatment, no more than 8 weeks.

• The proportion of subjects who are generally effective at the end of treatment and relapse at the end of treatment

  From Day 1 to the end of treatment, no more than 8 weeks.

• All-cause mortality at 30 days after initiation of ABCD

  From Day 1 to Day 30.

Study Arms (1)

Amphotericin B cholesteryl Sulfate Complex for Injection

EXPERIMENTAL

Subjects will receive ABCD intravenous injection.

Drug: Amphotericin B cholesteryl Sulfate Complex for Injection

Interventions

Amphotericin B cholesteryl Sulfate Complex for Injection DRUG

Intravenous injection (IV), once a day after reaching the recommended dose of 3.0-4.0 mg/kg for treatment. Subjects will receive ABCD intravenous therapy for at least 2 weeks, and the longest course of treatment will not exceed 6 weeks.

Amphotericin B cholesteryl Sulfate Complex for Injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old, male or female;
• Subjects who meet the EORTC-MSG diagnostic criteria and are diagnosed with invasive candidiasis (confirmed) or invasive aspergillus disease (confirmed or clinical) according to the Revised Definition of Invasive Mycosis: IC confirmed subjects are positive candida culture reports from blood or other sterile samples obtained within 48 hours prior to enrollment; Or the histopathological/cytopathological examination report of needle aspiration or biopsy specimens from normal sterile except mucosa within 2 weeks showed the presence of candida; IA confirmed subjects are defined as diseased tissue (sterile sampling) obtained within 4 weeks prior to enrollment with definite fungal presence (cytology, microscopy, or culture, etc.). The clinical diagnosis of IA includes at least one host factor, one clinical criterion, and one microbiological criterion (serum, sputum, bronchoalveolar lavage fluid, bronchial brush specimen, or sinus extract indicating positive Aspergillus GM test);
• All subjects agreed to use contraception from the time signed the informed consent to 6 weeks after the end of the last dose;
• Female subjects must meet one of the following conditions: have surgical sterilization; postmenopausal, menopause at least 1 year; or for those with fertility, must satisfy the following conditions: negative human chorionic gonadotropin (HCG) serum test results prior to enrollment; avoidance of sexual behavior throughout the study period, or agreement to use a recognized and highly effective contraceptive measure \[defined as being able to be used consistently and correctly with a failure rate of less than 1% per year, such as: condoms, combined hormones (including estrogen and progesterone) combining inhibit ovulation, progestin contraception combined with ovulation suppression, intrauterine device (IUD), intrauterine hormone release system (IUS), bilateral tubal ligation, bilateral vasectomy\], and the contraceptive methods remained unchanged throughout the study period;
• Male subjects must have been surgically sterilized or their female partners must have met any of #4 above, and their contraceptive methods remained unchanged during the study period;
• Subjects and/or guardian fully understand, voluntarily participate in this study and sign the informed consent form.

You may not qualify if:

• Allergic to amphotericin B drugs or cholesterol sulfate complex antifungal drugs;
• IC subjects received systemic antifungal therapy for ≥3 days within 1 week prior to enrollment (subjects with no improvement in symptoms of infection after treatment or with positive blood culture candida can still be enrolled; Subjects with neutropenia can use triazole prophylaxis for an unlimited days);
• IA subjects received systemic antifungal therapy for more than 96 hours within 1 week prior to enrollment (subjects with no improvement in symptoms of infection after treatment or those with positive microbiological criteria can still be enrolled), or prophylactic therapy for more than 13 days or common amphotericin B with cumulative dose of more than 10 mg/kg within 10 days prior to enrollment, or use amphotericin lipids with a cumulative dose of more than 15 mg/kg;
• Evidence of infection in subjects is limited to positive candida cultures in urine (other than those diagnosed with pyelonephritis), sputum and bronchoalveolar lavage fluid, catheter tops, drainage fluid, or other mucous membranes or superficial skin surfaces (e.g. vagina or other external genitalia, colon, oropharynx, esophagus, skin folds, nail beds, etc.);
• Subjects with suspected candida endocarditis, osteomyelitis, arthritis, endophthalmitis, liver and spleen abscess, suppurative thrombophlebitis, or central nervous system infection;
• Candida culture positive samples collected 24 hours after the non first placement of the catheter or drainage tube at the sterile site;
• Intravenous catheterization is associated with aggressive candidiasis in subjects whose catheters could not be removed or replaced during the study period;
• Subjects with chronic pulmonary aspergillus disease (duration ≥3 months), aspergilloma or allergic bronchopulmonary aspergillus disease;
• Subjects are known to have mixed invasive Candida or Aspergillus infections and/or are not sensitive to or resistant to amphotericin B treatment, such as subjects with invasive Aspergillus terreus and Aspergillus nidulans;
• Subjects who have been fitted with an artificial device (other than intravenous catheterization) and are suspected of being the source of infection and cannot have the device removed within 24 hours after enrollment;
• Subjects with abnormal liver function (aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥5 times the upper limit of normal without increase in total bilirubin, or ALT or AST increase 3 times the upper limit of normal with 1.5 times increase in total bilirubin);
• Subjects with renal dysfunction who require or are currently undergoing hemodialysis or peritoneal dialysis;
• Subjects with clinically significant hypokalemia (defined as serum potassium concentration \<3.2 mmol/L, or below the lower limit of normal in subjects undergoing digitalization ) and whose hypokalemia could not be corrected before beginning treatment;
• Subjects who plan to use prohibited drugs during the study;
• The expected survival time is less than 2 months;

Sponsors & Collaborators

• CSPC Ouyi Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

Location

MeSH Terms

Conditions

Candidiasis, Invasive

Interventions

Amphotericin B; Injections

Condition Hierarchy (Ancestors)

Candidiasis; Mycoses; Bacterial Infections and Mycoses; Infections; Invasive Fungal Infections

Intervention Hierarchy (Ancestors)

Macrolides; Polyketides; Lactones; Organic Chemicals; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Sizhou Feng

  Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

• Mei Hong

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

• Ming H

  Qilu Hospital of Shandong University

  PRINCIPAL INVESTIGATOR

• Suning Chen

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

• Jinhai Ren

  The Second Hospital of Hebei Medical University

  PRINCIPAL INVESTIGATOR

• Jishi Wang

  The Affiliated Hospital Of Guizhou Medical University

  PRINCIPAL INVESTIGATOR

• Fenge Yang

  Union Hospital Affiliated to Fujian Medical University

  PRINCIPAL INVESTIGATOR

• Fang Zhou

  Chinese the 960th Hospital of the Joint Logistics Support Department of the People's Liberation Army

  PRINCIPAL INVESTIGATOR

• Ming Jiang

  First Affiliated Hospital of Xinjiang Medical University

  PRINCIPAL INVESTIGATOR

• Baodong Ye

  The First Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine

  PRINCIPAL INVESTIGATOR

• Lina Zhang

  Henan Provincial People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2022
• First Posted: February 1, 2023
• Study Start: March 30, 2023
• Primary Completion: July 30, 2024
• Study Completion: March 31, 2025
• Last Updated: April 9, 2025

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)