Back to resultsAn Open-label Study of APX001 for Treatment of Patients With Candidemia/Invasive Candidiasis Caused by Candida Auris (APEX)
Primary Purpose
Candidemia, Invasive Candidiases, Candida Infection
Status
Completed
Phase
Phase 2
Locations
South Africa
Study Type
Interventional
Intervention
APX001
Sponsored by
About this trial
This is an interventional treatment trial for Candidemia
Eligibility Criteria
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
Sites / Locations
- Netcare Union Hospital Trauma Surgeons
- Milpark Academic Trauma Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
APX001
Arm Description
APX001 IV or oral for up to 42 days
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
All-Cause Mortality Through Study Day 30
Percentage of participants who died through study Day 30 is reported in this outcome measure.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04148287
Brief Title
An Open-label Study of APX001 for Treatment of Patients With Candidemia/Invasive Candidiasis Caused by Candida Auris
Acronym
APEX
Official Title
An Open-Label Study to Evaluate the Efficacy and Safety of APX001 in Patients With Candidemia and/or Invasive Candidiasis Caused by Candida Auris
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
December 13, 2019 (Actual)
Primary Completion Date
November 30, 2020 (Actual)
Study Completion Date
December 31, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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]).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Candidemia, Invasive Candidiases, Candida Infection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open-label, single arm intervention. All patients will receive APX001. On Days 1-3, APX001 will be administered intravenously. Thereafter, if the patient is able to take oral medication, APX001 tablets will be taken orally.
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
APX001
Arm Type
Experimental
Arm Description
APX001 IV or oral for up to 42 days
Intervention Type
Drug
Intervention Name(s)
APX001
Other Intervention Name(s)
fosmanogepix
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Treatment Success at End of Study Treatment (EOST) as Determined by Data Review Committee (DRC)
Description
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.
Time Frame
EOST: any day from Day 1 up to maximum of Day 42
Secondary Outcome Measure Information:
Title
Time to First Negative Blood Culture
Description
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.
Time Frame
Day 1 up to maximum of Day 42
Title
Percentage of Participants With Mycological Outcomes at EOST and 2 and 4 Weeks After EOST
Description
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.
Time Frame
EOST: any day from Day 1 up to maximum of Day 42, 2 and 4 weeks after EOST
Title
Percentage of Participants With Treatment Success at EOST Determined by Investigator
Description
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.
Time Frame
EOST: any day from Day 1 up to maximum of Day 42
Title
Percentage of Participants With Treatment Success at 2 and 4 Weeks After EOST Determined by Investigator and by the DRC
Description
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.
Time Frame
2 and 4 weeks after EOST (where EOST is any day from Day 1 up to maximum of Day 42)
Title
All-Cause Mortality Through Study Day 30
Description
Percentage of participants who died through study Day 30 is reported in this outcome measure.
Time Frame
Day 1 through Day 30
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
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.
Time Frame
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Netcare Union Hospital Trauma Surgeons
City
Alberton
State/Province
Gauteng
ZIP/Postal Code
1449
Country
South Africa
Facility Name
Milpark Academic Trauma Centre
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2193
Country
South Africa
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=APX001-203
Description
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Learn more about this trial
An Open-label Study of APX001 for Treatment of Patients With Candidemia/Invasive Candidiasis Caused by Candida Auris
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