An Efficacy and Safety Study of APX001 in Non-Neutropenic Patients With Candidemia

Sponsor
Amplyx Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03604705
Collaborator
(none)
21
20
1
21
1.1
0.1

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

Study Type:
Interventional
Actual Enrollment :
21 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label Study to Evaluate the Efficacy and Safety of APX001 in Non Neutropenic Patients With Candidemia, With or Without Invasive Candidiasis, Inclusive of Patients With Suspected Resistance to Standard of Care Antifungal Treatment
Actual Study Start Date :
Oct 3, 2018
Actual Primary Completion Date :
Mar 31, 2020
Actual Study Completion Date :
Jul 2, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: APX001 Treatment

Drug: APX001
APX001

Outcome Measures

Primary Outcome Measures

  1. 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

  1. 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.

  2. 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)]

  3. 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)]

  4. Overall Survival at Study Day 30 [Day 30]

  5. Number of Patients With Treatment Emergent Adverse Events (TEAEs) [One to forty-nine days]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Responsible Party:
Amplyx Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03604705
Other Study ID Numbers:
  • APX001-201
First Posted:
Jul 27, 2018
Last Update Posted:
Aug 5, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

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

1. Primary Outcome
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%
2. Secondary Outcome
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)
3. Secondary Outcome
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
4. Secondary Outcome
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
5. Secondary Outcome
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%
6. Secondary Outcome
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

[Not Specified]

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
Email mhodges@amplyx.com
Responsible Party:
Amplyx Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03604705
Other Study ID Numbers:
  • APX001-201
First Posted:
Jul 27, 2018
Last Update Posted:
Aug 5, 2021
Last Verified:
Jul 1, 2021