Clinical trial NCT04148287: An Open-label Study of APX001 for Treatment of Patients With Candidemia/Invasive Candidiasis Caused by Candida Auris
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Candidemia
Invasive Candidiases
Candida Infection
Lead sponsor: Basilea Pharmaceutica
Sponsor class: INDUSTRY
First posted: 2019-11-01
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: TREATMENT

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 \[168 hours prior to Baseline\]).

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

Primary outcomes:
measure: Percentage of Participants With Treatment Success at End of Study Treatment (EOST) as Determined by Data Review Committee (DRC)
timeFrame: EOST: any day from Day 1 up to maximum of Day 42
Secondary outcomes:
measure: Time to First Negative Blood Culture
timeFrame: Day 1 up to maximum of Day 42
measure: Percentage of Participants With Mycological Outcomes at EOST and 2 and 4 Weeks After EOST
timeFrame: EOST: any day from Day 1 up to maximum of Day 42, 2 and 4 weeks after EOST
measure: Percentage of Participants With Treatment Success at EOST Determined by Investigator
timeFrame: EOST: any day from Day 1 up to maximum of Day 42
measure: Percentage of Participants With Treatment Success at 2 and 4 Weeks After EOST Determined by Investigator and by the DRC
timeFrame: 2 and 4 weeks after EOST (where EOST is any day from Day 1 up to maximum of Day 42)
measure: All-Cause Mortality Through Study Day 30
timeFrame: Day 1 through Day 30
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: 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)
Other outcomes:
Locations:
city: Alberton
country: South Africa
facility: Netcare Union Hospital Trauma Surgeons
state: Gauteng
city: Johannesburg
country: South Africa
facility: Milpark Academic Trauma Centre
state: Gauteng
Study officials:
affiliation: Basilea Pharmaceutica International Ltd, Allschwil
name: Marc Engelhardt
role: STUDY_DIRECTOR
References: