An Open-label Study of APX001 for Treatment of Patients With Candidemia/Invasive Candidiasis Caused by Candida Auris (APEX)

An Open-Label Study to Evaluate the Efficacy and Safety of APX001 in Patients With Candidemia and/or Invasive Candidiasis Caused by Candida Auris

This is a multicenter, open-label, single arm study to evaluate the efficacy and safety of APX001 for the treatment of candidemia and/or invasive candidiasis caused by C. auris in patients aged 18 years and over with limited antifungal treatment options.

Study Overview

• Status: Completed
• Conditions: Candidemia; Candida Infection; Invasive Candidiases
• Intervention / Treatment: Drug: APX001

Detailed Description

This is a multicenter, open-label, non-comparative, single arm study to evaluate the efficacy and safety of APX001 for the treatment of candidemia and/or invasive candidiasis caused by C. auris in patients aged 18 years and over with limited antifungal treatment options. The Study Drug Treatment Period will be up to a maximum of 42 days (inclusive of the loading dose [Study Day 1]). There will be a Follow up Period of 4 weeks (+4 days) after EOST. The total duration of participation in the study is up to approximately 10.5 weeks (inclusive of the Screening Period [168 hours prior to Baseline]).

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Africa
  • Gauteng
    • Alberton, Gauteng, South Africa, 1449
      • Netcare Union Hospital Trauma Surgeons
    • Johannesburg, Gauteng, South Africa, 2193
      • Milpark Academic Trauma Centre

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Limited or no treatment options due to resistance, contraindication, intolerance or lack of clinical response to standard of care antifungal therapy, as advocated by the relevant regional/country treatment guidelines
• Established mycological and clinical diagnosis of candidemia and/or invasive candidiasis caused by Candida auris
• Able to have pre-existing intravascular catheters removed and replaced (if necessary)
• Females of childbearing potential with male partners, and males with female partner(s) of childbearing potential, must agree to use 2 forms of highly effective contraception throughout the duration of the study and for 90 days following the last study drug administration. Females of childbearing potential must have a negative urine pregnancy test within 96 hours prior study entry.
• Wiling to participate in the study, willing to give written informed consent, and willing to comply with the study restrictions; where permitted by local regulations, written informed consent from a legal authorized representative (LAR) will be obtained for patients who are unable to give consent

Exclusion Criteria:

• Life expectancy of less than 7 days in the opinion of the Investigator
• Human immunodeficiency virus-infected patients who are receiving antiretroviral therapy that are moderate to strong inducers of CYP3A4, or who have detectable viremia, or who have had an active opportunistic infection within 6 months prior
• Alanine aminotransferase or aspartate aminotransferase greater than or equal to 5 times the upper limit of normal
• Total bilirubin greater than 3 time the upper limit of normal, unless isolated hyperbilirubinemia or due to documented Gilbert's disease
• Pregnant or lactating female patient
• Inappropriate fungal infection source control
• Investigational drug administered within 30 days prior to dosing or five half-lives whichever is longer
• Diagnosis of deep-seated Candida-related infections causing hardware associated septic arthritis, osteomyelitis, endocarditis, myocarditis, hepatosplenic candidiasis, or a central nervous system infection or site of infection that would require antifungal therapy to exceed the maximal duration of study drug treatment

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: APX001; APX001 IV or oral for up to 42 days	Drug: APX001; Day 1: APX001 1000 mg IV BID over a 3-hour infusion Days 2-3: APX001 600 mg IV QD over a 3-hour infusion Days 4 - 42: APX001 600 mg IV QD over a 3-hour infusion or APX001 800 mg QD oral.; Other Names: fosmanogepix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Success at End of Study Treatment (EOST) as Determined by Data Review Committee (DRC)	Treatment success was defined as meeting all of the following criteria: 1) Two consecutive blood cultures negative for Candida species, and/or for participants with a deep-seated site of infection, at least 1 negative tissue culture or aspirate/fluid culture. For participants with a deep-seated site of infection involving visceral organs from which a tissue culture was not obtainable, resolution of the attributable clinical signs of infection recorded at Baseline, and as applicable, radiological improvement associated with the site of infection. 2) Alive at EOST and 3) No concomitant use of any other systemic antifungal therapies through EOST.	EOST: any day from Day 1 up to maximum of Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Negative Blood Culture	Time to first negative blood culture was defined as the number of days from date of first dose of study drug to the date of first negative blood culture plus 1. Participants without a negative blood culture at post-baseline visits were censored at the last assessment date. Kaplan-Meier method was used for analysis.	Day 1 up to maximum of Day 42
Percentage of Participants With Mycological Outcomes at EOST and 2 and 4 Weeks After EOST	Mycological outcomes were determined based on eradication and presumed eradication. Eradication was defined as a negative blood (and/or other infection site) culture(s) for Candida species. Presumed eradication (applicable to invasive candidiasis) was defined as clinical resolution of invasive Candida species infection where tissue samples were unavailable. These would be applicable only if there were no concomitant or additional systemic antifungal usage.	EOST: any day from Day 1 up to maximum of Day 42, 2 and 4 weeks after EOST
Percentage of Participants With Treatment Success at EOST Determined by Investigator	Treatment success was defined as meeting all of the following criteria: 1) Two consecutive blood cultures negative for Candida species, and/or for participants with a deep-seated site of infection, at least 1 negative tissue culture or aspirate/fluid culture. For participants with a deep-seated site of infection involving visceral organs from which a tissue culture was not obtainable, resolution of the attributable clinical signs of infection recorded at Baseline, and as applicable, radiological improvement associated with the site of infection. 2) Alive at EOST and 3) No concomitant use of any other systemic antifungal therapies through EOST.	EOST: any day from Day 1 up to maximum of Day 42
Percentage of Participants With Treatment Success at 2 and 4 Weeks After EOST Determined by Investigator and by the DRC	Treatment success was defined as meeting all of the following criteria: 1) Two consecutive blood cultures negative for Candida species, and/or for participants with a deep-seated site of infection, at least 1 negative tissue culture or aspirate/fluid culture. For participants with a deep-seated site of infection involving visceral organs from which a tissue culture was not obtainable, resolution of the attributable clinical signs of infection recorded at Baseline, and as applicable, radiological improvement associated with the site of infection. 2) Alive at EOST and 3) No concomitant use of any other systemic antifungal therapies through EOST.	2 and 4 weeks after EOST (where EOST is any day from Day 1 up to maximum of Day 42)
All-Cause Mortality Through Study Day 30	Percentage of participants who died through study Day 30 is reported in this outcome measure.	Day 1 through Day 30
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between first dose of study drug and up to Week 4 (+4 days) post last dose of study drug that were absent before treatment or that worsened relative to pretreatment state.	Day 1 up to maximum of 32 days of follow up post last dose of study drug, where maximum treatment duration was 42 days (maximum up to 74 days)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2019
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): April 4, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Mycoses; Invasive Fungal Infections; Fungemia; Candidiasis; Candidemia; Candidiasis, Invasive
• Other Study ID Numbers: APX001-203; C4791011 (Other Identifier: Alias Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• IPD Sharing Time Frame: Approximately 6 months following the last patient's last visit in the study.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes