Candidemia
Conditions
Brief summary
This is a multicenter, open-label, non-comparative, single-arm study to evaluate the efficacy and safety of APX001 for the first-line treatment for candidemia including suspected or confirmed antifungal-resistant candidemia in non-neutropenic patients 18 yeas of age and older. Suspicion of antifungal-resistant candidemia is sufficient (documented resistance is not required for enrollment). The Study Drug Treatment Period of APX001 will be a maximum of 14 days. After completion of 14 days study drug therapy, if further antifungal treatment is indicated to complete treatment of candidemia in accordance with standard practice guidelines, fluconazole (unless susceptibility results warrant alternative antifungal therapy) may commence for up to a further 7 days. There will be a Follow up Period of 4 weeks (+4 days) after EOT. The total duration of participation in the study is up to approximately 7.5 weeks. This study will be conducted at approximately 20 sites in the United States and globally.
Interventions
DRUGAPX001
APX001
Sponsors
Basilea Pharmaceutica
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Provision of written consent * Adults ages 18 and above male or female * New diagnosis of candidemia * Able to have pre-existing intravascular catheters removed and replaced (as necessary) Key
Exclusion criteria
* neutropenia * deep-seated Candida-related infections * hepatosplenic candidiasis * received more than 2 days of prior systemic antifungal treatment for current candidemia episode * severe hepatic impairment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Success at End of Study Treatment (EOST) as Determined by the Data Review Committee (DRC) | One to forty-two days | Treatment Success is defined as meeting all of the following criteria: Two consecutive blood cultures negative for Candida spp. Alive at EOST No concomitant use of any other systemic antifungal therapies through end of study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Negative Blood Culture | One to forty-nine days | Time to first negative blood culture was defined as the number of days from first dose date of study drug to the date of first post-Baseline negative blood culture + 1. Patients without a negative blood culture at post-Baseline visits were censored at the last assessment date. |
| Percentage of Patients With Mycological Outcomes at End of Study Treatment (EOST), End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT) | End of study treatment (EOST), end of treatment (EOT), and 2 and 4 weeks after end of treatment (EOT) | — |
| Percentage of Patients With Treatment Success at End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT) | 2 and 4 weeks after end of treatment (EOT) | — |
| Overall Survival at Study Day 30 | Day 30 | — |
| Number of Patients With Treatment Emergent Adverse Events (TEAEs) | One to forty-nine days | — |
Countries
Belgium, Germany, Israel, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Period - MITT Evaluation of APX001 for the first-line treatment for candidemia, including suspected or confirmed antifungal-resistant candidemia, in non-neutropenic patients ≥ 18 years of age who had at least 1 positive blood culture within the 96 hours prior to starting study drug. Modified Intent-to-Treat (MITT) Population. The MITT Population contained 20 (95.2%) patients. | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Treatment Period - MITT |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 19 Participants |
| Region of Enrollment Belgium | 7 participants |
| Region of Enrollment Israel | 9 participants |
| Region of Enrollment Spain | 1 participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 21 |
| other Total, other adverse events | 20 / 21 |
| serious Total, serious adverse events | 9 / 21 |
Outcome results
Primary
Treatment Success at End of Study Treatment (EOST) as Determined by the Data Review Committee (DRC)
Treatment Success is defined as meeting all of the following criteria: Two consecutive blood cultures negative for Candida spp. Alive at EOST No concomitant use of any other systemic antifungal therapies through end of study treatment
Time frame: One to forty-two days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Period - MITT | Treatment Success at End of Study Treatment (EOST) as Determined by the Data Review Committee (DRC) | 16 Participants |
Secondary
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Time frame: One to forty-nine days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Period - MITT | Number of Patients With Treatment Emergent Adverse Events (TEAEs) | 20 Participants |
Secondary
Overall Survival at Study Day 30
Time frame: Day 30
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Period - MITT | Overall Survival at Study Day 30 | 17 Participants |
Secondary
Percentage of Patients With Mycological Outcomes at End of Study Treatment (EOST), End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT)
Time frame: End of study treatment (EOST), end of treatment (EOT), and 2 and 4 weeks after end of treatment (EOT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Period - MITT | Percentage of Patients With Mycological Outcomes at End of Study Treatment (EOST), End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT) | 16 Participants |
| EOT (End of Antifungal Treatment) | Percentage of Patients With Mycological Outcomes at End of Study Treatment (EOST), End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT) | 15 Participants |
| Follow-up 2 Weeks After EOT | Percentage of Patients With Mycological Outcomes at End of Study Treatment (EOST), End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT) | 1 Participants |
| Follow-up 4 Weeks After EOT | Percentage of Patients With Mycological Outcomes at End of Study Treatment (EOST), End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT) | 0 Participants |
Secondary
Percentage of Patients With Treatment Success at End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT)
Time frame: 2 and 4 weeks after end of treatment (EOT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Period - MITT | Percentage of Patients With Treatment Success at End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT) | 60.0 percentage of participants |
| EOT (End of Antifungal Treatment) | Percentage of Patients With Treatment Success at End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT) | 55.0 percentage of participants |
Secondary
Time to First Negative Blood Culture
Time to first negative blood culture was defined as the number of days from first dose date of study drug to the date of first post-Baseline negative blood culture + 1. Patients without a negative blood culture at post-Baseline visits were censored at the last assessment date.
Time frame: One to forty-nine days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Period - MITT | Time to First Negative Blood Culture | 2.4 Days | Standard Deviation 1.13 |