An Efficacy and Safety Study of APX001 in Non-Neutropenic Patients With Candidemia
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: APX001 Treatment
|
Drug: APX001
APX001
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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]
Eligibility Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Alabama at Birmingham (UAB) | Birmingham | Alabama | United States | 35249 |
2 | University of California, Davis | Davis | California | United States | 95616 |
3 | Augusta University (Georgia Regents University) | Augusta | Georgia | United States | 30901 |
4 | University of Chicago | Chicago | Illinois | United States | 60637 |
5 | Washington University | Saint Louis | Missouri | United States | 63110 |
6 | Duke University Hospital Medical Center | Durham | North Carolina | United States | 27710 |
7 | University of Texas- Health Science Center and Medical School at Houston | Houston | Texas | United States | 77030 |
8 | Institut Jules Bordet | Brussels | Belgium | ||
9 | Universite Libre de Bruxelles (ULB) - Hopital Erasme | Brussels | Belgium | ||
10 | CHU de Charleroi - Hopital Civil Marie Curie | Lodelinsart | Belgium | ||
11 | University Hospital Mont-Godinne | Yvoir | Belgium | ||
12 | Klinik I fur Innere Medizin- Uniklinik Koln | Cologne | Germany | ||
13 | University Hospital Heidelberg | Heidelberg | Germany | ||
14 | Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz - III. Medizinische Klinik Haematologie/Onkologie | Mainz | Germany | ||
15 | Rambam Medical Center | Haifa | Israel | ||
16 | Sourasky Medical Center | Tel Aviv | Israel | ||
17 | Sheba Medical Center | Tel HaShomer | Israel | ||
18 | Hospital Universitario Mutua de Terrassa | Terrassa | Barcelona | Spain | |
19 | Hospital General Universitario de Alicante | Alicante | Spain | ||
20 | Hospital VLL D Hebron | Barcelona | Spain |
Sponsors and Collaborators
- Amplyx Pharmaceuticals
Investigators
- Study Director: Michael Hodges, MD, Amplyx Pharmaceuticals
Study Documents (Full-Text)
More Information
Publications
None provided.- APX001-201
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | APX001 Treatment |
---|---|
Arm/Group Description | APX001: APX001 IV administration followed by APX001 oral tablet administration |
Period Title: Overall Study | |
STARTED | 21 |
COMPLETED | 20 |
NOT COMPLETED | 1 |
Baseline Characteristics
Arm/Group Title | Treatment Period - MITT |
---|---|
Arm/Group Description | 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. |
Overall Participants | 20 |
Age (Count of Participants) | |
<=18 years |
0
0%
|
Between 18 and 65 years |
10
50%
|
>=65 years |
10
50%
|
Sex: Female, Male (Count of Participants) | |
Female |
7
35%
|
Male |
13
65%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
0
0%
|
Not Hispanic or Latino |
18
90%
|
Unknown or Not Reported |
2
10%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
Black or African American |
1
5%
|
White |
19
95%
|
More than one race |
0
0%
|
Unknown or Not Reported |
0
0%
|
Region of Enrollment (participants) [Number] | |
Belgium |
7
35%
|
United States |
3
15%
|
Israel |
9
45%
|
Spain |
1
5%
|
Outcome Measures
Title | Treatment Success at End of Study Treatment (EOST) as Determined by the Data Review Committee (DRC) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment Period - MITT |
---|---|
Arm/Group Description | Treatment Success was defined as meeting all of the following criteria: 1) 2 consecutive blood cultures were negative for Candida spp.; 2) Alive at EOST; and 3) No concomitant use of any other systemic antifungal therapies through EOST. Treatment Failure is defined as any case that does not meet the criteria for Treatment Success. |
Measure Participants | 20 |
Count of Participants [Participants] |
16
80%
|
Title | Time to First Negative Blood Culture |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | MITT Population |
---|---|
Arm/Group Description | MITT = Modified Intent-to-Treat population |
Measure Participants | 20 |
Mean (Standard Deviation) [Days] |
2.4
(1.13)
|
Title | 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) |
---|---|
Description | |
Time Frame | End of study treatment (EOST), end of treatment (EOT), and 2 and 4 weeks after end of treatment (EOT) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | EOST (End of Study Drug Treatment) | EOT (End of Antifungal Treatment) | Follow-up 2 Weeks After EOT | Follow-up 4 Weeks After EOT |
---|---|---|---|---|
Arm/Group Description | Eradication | Eradication | Recurrence | Recurrence |
Measure Participants | 20 | 20 | 20 | 20 |
Count of Participants [Participants] |
16
80%
|
15
NaN
|
1
NaN
|
0
NaN
|
Title | Percentage of Patients With Treatment Success at End of Treatment (EOT), and 2 and 4 Weeks After End of Treatment (EOT) |
---|---|
Description | |
Time Frame | 2 and 4 weeks after end of treatment (EOT) |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Treatment Success 2 Weeks After EOT | Treatment Success 4 Weeks After EOT |
---|---|---|
Arm/Group Description | Treatment Success determined by the DRC by visit for the MITT Population. | Treatment success determined by the DRC by visit for the MITT Population. |
Measure Participants | 20 | 20 |
Number [percentage of participants] |
60.0
300%
|
55.0
NaN
|
Title | Overall Survival at Study Day 30 |
---|---|
Description | |
Time Frame | Day 30 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | MITT Population |
---|---|
Arm/Group Description | MITT = Modified Intent-to-Treat population |
Measure Participants | 20 |
Count of Participants [Participants] |
17
85%
|
Title | Number of Patients With Treatment Emergent Adverse Events (TEAEs) |
---|---|
Description | |
Time Frame | One to forty-nine days |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Safety Population |
---|---|
Arm/Group Description | Twenty-one patients were dosed with APX001 and composed the ITT/Safety Population. |
Measure Participants | 21 |
Count of Participants [Participants] |
20
100%
|
Adverse Events
Time Frame | One to forty-nine days | |
---|---|---|
Adverse Event Reporting Description | ||
Arm/Group Title | Safety Population | |
Arm/Group Description | Twenty-one patients were dosed with APX001 and composed the ITT/Safety Population. | |
All Cause Mortality |
||
Safety Population | ||
Affected / at Risk (%) | # Events | |
Total | 5/21 (23.8%) | |
Serious Adverse Events |
||
Safety Population | ||
Affected / at Risk (%) | # Events | |
Total | 9/21 (42.9%) | |
Blood and lymphatic system disorders | ||
Leukopenia | 1/21 (4.8%) | 1 |
Cardiac disorders | ||
Cardiac failure congestive | 1/21 (4.8%) | 1 |
Cardio-respiratory arrest | 1/21 (4.8%) | 1 |
Gastrointestinal disorders | ||
Gastrointestinal fistula | 1/21 (4.8%) | 1 |
General disorders | ||
Euthanasia | 1/21 (4.8%) | 1 |
General physical health deterioration | 1/21 (4.8%) | 1 |
Infections and infestations | ||
Septic shock | 2/21 (9.5%) | 2 |
Bacteraemia | 1/21 (4.8%) | 1 |
Bacterial sepsis | 1/21 (4.8%) | 1 |
Enterobacter sepsis | 1/21 (4.8%) | 1 |
Necrotising fasciitis | 1/21 (4.8%) | 1 |
Sepsis | 1/21 (4.8%) | 1 |
Stenotrophomonas sepsis | 1/21 (4.8%) | 1 |
Systemic candida | 1/21 (4.8%) | 1 |
Urinary tract infection bacterial | 1/21 (4.8%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||
Acute respiratory failure | 1/21 (4.8%) | 1 |
Interstitial lung disease | 1/21 (4.8%) | 1 |
Other (Not Including Serious) Adverse Events |
||
Safety Population | ||
Affected / at Risk (%) | # Events | |
Total | 20/21 (95.2%) | |
Gastrointestinal disorders | ||
Diarrhoea | 3/21 (14.3%) | 3 |
Vomiting | 3/21 (14.3%) | 3 |
Nausea | 2/21 (9.5%) | 2 |
General disorders | ||
Oedema peripheral | 3/21 (14.3%) | 3 |
Pyrexia | 2/21 (9.5%) | 2 |
Infections and infestations | ||
Bacteraemia | 2/21 (9.5%) | 2 |
Septic shock | 2/21 (9.5%) | 2 |
Renal and urinary disorders | ||
Acute kidney injury | 2/21 (9.5%) | 2 |
Hydronephrosis | 2/21 (9.5%) | 2 |
Renal failure | 2/21 (9.5%) | 2 |
Respiratory, thoracic and mediastinal disorders | ||
Pleural effusion | 3/21 (14.3%) | 3 |
Dyspnoea | 2/21 (9.5%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Chief Medical Officer |
---|---|
Organization | Amplyx Pharmaceuticals |
Phone | 8588427854 |
mhodges@amplyx.com |
- APX001-201