Clinical Study of ABCD in the Treatment of Cryptococcal Meningitis

Clinical Study of Amphotericin B Colloidal Dispersion (ABCD) in the Treatment of Cryptococcal Meningitis

To evaluate the efficacy and safety of ABCD in the treatment of cryptococcal meningitis in non-HIV patients at week 4, the end of induction therapy, week 10 and the end of consolidation therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Cryptococcal Meningitis
• Intervention / Treatment: Drug: Amphotericin B Colloidal Dispersion; Drug: flucytosine; Drug: fluconazole

Detailed Description

This study is a multi-center, single-arm clinical study. The objective is to evaluate the efficacy and safety of ABCD in the treatment of cryptococcal meningitis in non-HIV patients. Qualified subjects shall receive cryptococcus induction therapy with ABCD combined with flucytosine for at least 4 weeks, or termination of treatment early at the investigator's discretion. Efficacy and safety are followed up at week 4 (day 28), the end of induction therapy, week 10 (day 70) and the end of consolidation therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wei Cao, PhD; Phone Number: 010-69156114; Email: wcao_pumch@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
      • Contact: Wei Cao, PhD; Phone Number: 010-69156114; Email: wcao_pumch@163.com
      • Principal Investigator: Taisheng Li, PhD
      • Principal Investigator: Wei Cao, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥18 years old and ≤70 years old, no gender limitation;
• Diagnosis of cryptococcal meningitis (with or without other cryptococcal lesions) based on CSF culture and/or CSF ink staining smear and/or CSF antigen testing;
• The researcher believes that patients can benefit from participating in this study;
• The subjects voluntarily participated in the study and signed the informed consent.

Exclusion Criteria:

• Patients with other invasive fungal diseases;
• HIV infected patients;
• Patients who received intravenous polyene treatment within the past 6 months;
• Allergic to Amphotericin B Colloidal Dispersion or other ingredients in this product;
• Patients with abnormal liver function [aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >＝5 times the upper limit of normal value (ULN) without total bilirubin elevation, or ALT or AST >＝ 3 times ULN with total bilirubin >＝ 1.5 times];
• Patients with impaired renal function (renal function index blood creatinine (Cr) is more than 2 times higher than ULN, or 24-hour urine creatinine clearance rate （Ccr） is less than 50ml/min), or patients requiring/undergoing hemodialysis or peritoneal dialysis;
• Pregnant women, breast-feeding women and women of childbearing age who were unable to take effective contraceptive measures during the study period;
• Conditions considered unsuitable for the study by the investigator, such as concomitancy of severe organ insufficiency, clinically significant laboratory abnormalities, comprehension or compliance problems, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ABCD treatment; In this single-arm research, patients were treated with ABCD 3.0-4.0 mg/kg/d (subject to adjustment, maximum dose not exceeding 6.0 mg/kg/d) combined with flucytosine 100 mg/kg/d for induction therapy of cryptococcal meningitis. The course of induction therapy is at least four weeks. Then, patients were treated with Fluconazole (400-600 mg/d) ± flucytosine (100 mg/kg/d) for consolidation therapy for at least 6 weeks.

Drug: Amphotericin B Colloidal Dispersion; Amphotericin B Colloidal Dispersion 3.0-4.0 mg/kg/d (subject to adjustment, maximum dose not exceeding 6.0 mg/kg/d) . The course of induction therapy is at least four weeks.; Other Names: Amphotericin B Cholesteryl Sulfate Complex for Injection; Drug: flucytosine; Flucytosine 100 mg/kg/d for induction therapy and consolidation therapy of cryptococcal meningitis. The course of induction therapy is at least four weeks, and consolidation therapy for at least 6 weeks.; Other Names: fluorocytosine; Drug: fluconazole; Fluconazole (400-600 mg/d) for consolidation therapy for at least 6 weeks.; Other Names: Diflucan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with complete or partial response at the end of induction therapy	Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable. Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.	From enrollment to the end of induction therapy (about 4-6 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with complete or partial response at 4 weeks	Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable. Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.	At the 4 weeks of treatment
Proportion of patients with complete or partial response at 10 weeks	Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable. Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.	At the 10 weeks of treatment
Proportion of patients with complete or partial response at the end of consolidation therapy	Complete response: live during the observation period, patients with cryptococcus meningitis all the clinical signs and symptoms disappeared, a significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable. Partial response: patient survival during the observation period, cryptococcal meningitis clinical signs and symptoms improved, all the significant reduction in the cerebrospinal fluid cryptococcal antigen test results and/or CSF cryptococcus training and/or ink staining (two consecutive tests, one week interval) results overcast, and abnormal head MRI/CT (if exist in baseline) improved or stable.	At the end of the consolidation therapy (about 12 weeks)
Cryptococcus antigen titer	Diachronic changes in antigenic titers of Cryptococcus	1,2,3,4,10 weeks
Duration of the cryptococcal meningitis	The time from this hospitalization to the end of consolidation therapy.	At the end of the consolidation therapy (about 12 weeks)
Adverse events	Incidence and severity of adverse events during treatment, evaluated according to NCI-CTCAE Ver. 5.0.	about 12 weeks

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: CSPC Ouyi Pharmaceutical Group Co., Ltd.
• Investigators: Principal Investigator: Taisheng Li, PhD, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 22, 2022
• Primary Completion (Anticipated): February 28, 2023
• Study Completion (Anticipated): April 30, 2023

Study Registration Dates

• First Submitted: July 1, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (Actual): July 22, 2022

Study Record Updates

• Last Update Posted (Actual): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: cryptococcal meningitis; Amphotericin B Colloidal Dispersion; non-HIV patients
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Bacterial Infections and Mycoses; Mycoses; Meningitis, Fungal; Central Nervous System Fungal Infections; Cryptococcosis; Meningitis; Meningitis, Cryptococcal; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Protective Agents; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Serine Proteinase Inhibitors; Steroid Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Anticarcinogenic Agents; Amebicides; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole; Flucytosine; Amphotericin B; Liposomal amphotericin B; Cholesteryl sulfate
• Other Study ID Numbers: CSPC-ABCD-K09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No