Back to resultsOpen-label Study of APX001 for Treatment of Patients With Invasive Mold Infections Caused by Aspergillus or Rare Molds (AEGIS)
Primary Purpose
Invasive Fungal Infections
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
fosmanogepix
Sponsored by
About this trial
This is an interventional treatment trial for Invasive Fungal Infections focused on measuring APX001, APX001A, fosmanogepix, manogepix, aspergillus, aspergillosis, covid, covid19, mold, mould, pulmonary aspergillosis, pulmonary aspergillus, galactomannan, Karius, SARS-CoV-2, fusarium, mucorales, mucor, rhizopus, scedosporium, fungal disease, invasive fungal disease, EORTC
Eligibility Criteria
Inclusion Criteria:
- Males or females, 18 years or older.
- Patients with proven or probable IMI caused by Aspergillus spp. Patients who present with IMI due to other filamentous fungi (eg, Scedosporium spp., Fusarium spp., and Mucorales fungi such as Mucor spp. or Rhizopus spp.) may also be enrolled.
- Have limited or no treatment options due to documented or anticipated resistance, contraindication, intolerance, or lack of clinical response to SOC antifungal therapy, as advocated by the relevant regional/country treatment guidelines.
- Patients where the Investigator considers that there is a potential advantage of using APX001 over current SOC (eg, broad spectrum of activity, emergence of IMI during antifungal prophylaxis, activity against resistant mold pathogens, IV and PO formulations, favorable DDI profile, favorable hepatic and renal safety profile, wide tissue distribution including brain), and/or where the SOC antifungal therapy carries significant risk of toxicity or treatment failure (eg, DDI risk, safety/toxicity risk, site of infection not accessible by SOC).
Exclusion Criteria:
- Refractory hematologic malignancy.
- Chronic aspergillosis, aspergilloma, or allergic bronchopulmonary aspergillosis.
- Treatment with systemic (PO, IV, or inhaled) mold active antifungal therapy for 120 hours immediately before initial dosing. Note: patients with invasive fungal infection caused by a mold with documented resistance to or lack of coverage by the prior SOC in question, may have received >120 hours prior treatment and remain eligible for the study.
- Evidence of significant hepatic dysfunction.
Sites / Locations
- City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
- IP Address : City of Hope Investigational Drug Services (IDS)
- Duke Department of Pharmacy/Investigational Drug Service (IDS)
- Duke Medicine Pavilion
- Duke University Medical Center (Duke South Clinic)
- Duke University Medical Center(Duke Hospital)
- Cliniques Universitaires de Bruxelles Hôpital Erasme - Department of Infectious Diseases
- UZ Leuven - Department of Haematology
- CHU UCL Namur - Mont- Godinne University Hospital - Intensive Care Unit
- Klinikum Neuperlach, Klinik fur Hamatologie und Onkologie
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz III
- Pharmacy
- Rambam Medical Center
- Pharmacy
- Sheba Medical Center, Tel Hashomer
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A: fosmanogepix (APX001)
Cohort B: fosmanogepix (APX001)
Arm Description
Outcomes
Primary Outcome Measures
Percentage of Participants Who Died After the First Dose of Study Drug Through Day 42
Percentage of participants who died after first dose in the study through Day 42 were reported in this outcome measure. This outcome measure included all deaths from Day 1 through Day 42.
Secondary Outcome Measures
Percentage of Participants With Global Response Based on Data Review Committee (DRC) Assessment at End of Study Drug Treatment (EOST)
Global response was classified as treatment success (complete or partial response [CR or PR]) or treatment failure (stable response [SR], progression of fungal disease [PD], or death) as determined by DRC. CR: survival within prespecified period of observation (PPOB), resolution of all attributable (att) symptoms and signs of disease and radiological (rad) abnormalities, and mycological (myco) evidence of eradication of disease. PR: survival within POB, improvement in att symptoms and signs of disease and rad abnormalities, and evidence of clearance of cultures or reduction of fungal burden. SR: survival within PPOB, minor or no improvement in fungal disease but no evidence of progression based on composite of clinical, rad and myco criteria, PD or death. PD: evidence of progressive fungal disease based on composite of clinical, rad and myco criteria. Death: death during PPOB, regardless of attribution. Data is presented for EOST which could have preceded Day 42 for some participants.
Percentage of Participants With Treatment Success or Treatment Failure for Global Response Based on Data Review Committee (DRC) Assessment at End of Study Drug Treatment (EOST)
Global response was classified as treatment success (CR or PR) or treatment failure (SR, PD or death) as determined by DRC. CR: survival within prespecified POB, resolution of all attributable symptoms and signs of disease and rad abnormalities and myco evidence of eradication of disease. PR: survival within prespecified POB, improvement in attributable symptoms and signs of disease and rad abnormalities and evidence of clearance of cultures or reduction of fungal burden. SR: survival within prespecified POB, minor or no improvement in fungal disease, but no evidence of progression, based on composite of clinical, rad, and myco criteria, PD or death. PD: evidence of PD based on a composite of clinical, rad, and myco criteria. Death: death during prespecified period of evaluation, regardless of attribution. Percentage of participants with treatment success (CR, PR) and treatment failure (SR, PD, death) along with two-sided exact binomial 80% confidence interval is presented.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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 4 weeks post last dose of study treatment that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. AEs included SAEs and all non-SAEs.
Number of Participants With Clinically Significant Abnormality in Vital Signs
Vital signs included body temperature, blood pressure, heart rate, respiratory rate, and oxygen saturation. Number of participants with clinically significant abnormality in vital signs as judged by investigator were reported in this outcome measure.
Number of Participants With Clinically Significant Abnormality in Laboratory Test Evaluations
Clinical laboratory assessments included serum chemistry (bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, creatine kinase), hematology (including hemoglobin, hematocrit, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils and monocytes), coagulation (including Prothrombin time [PT]/ International normalized ratio [INR]), and urinalysis. Number of participants with clinically significant abnormality in any laboratory parameter as judged by investigator and reported as adverse events were presented.
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings
ECG parameters included PR interval, QRS interval, QT interval, QT interval corrected using the Fridericia's formula (QTcF), QT interval corrected using the Bazett's formula (QTcB), RR interval and heart rate. Number of participants with clinically significant abnormal ECG findings as judged by investigator were presented.
Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examinations
Physical examination included an assessment of general appearance, skin, eyes, heart, chest, abdomen, and a neurological examination. Components of the neurological examination included cranial nerve, sensory, and motor examination; reflex and gait testing; and coordination assessment. Clinically significant changes were judged by investigator.
Plasma Concentrations of Fosmanogepix
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04240886
Brief Title
Open-label Study of APX001 for Treatment of Patients With Invasive Mold Infections Caused by Aspergillus or Rare Molds
Acronym
AEGIS
Official Title
A Phase 2, Open-Label Study to Evaluate the Safety and Efficacy of APX001 in the Treatment of Patients With Invasive Mold Infections Caused by Aspergillus Species or Rare Molds
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Terminated
Why Stopped
The Sponsor (Amplyx, a Pfizer company) made a strategic decision to terminate the study, in order to prioritize a randomized comparative Phase 3 trial in the same indication. This decision was not based on any safety concerns
Study Start Date
January 4, 2020 (Actual)
Primary Completion Date
March 29, 2022 (Actual)
Study Completion Date
May 9, 2022 (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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 2, multicenter study to evaluate APX001 for the treatment of invasive fungal infections caused by Aspergillus spp. or rare molds (eg, Scedosporium spp., Fusarium spp., and Mucorales fungi).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Fungal Infections
Keywords
APX001, APX001A, fosmanogepix, manogepix, aspergillus, aspergillosis, covid, covid19, mold, mould, pulmonary aspergillosis, pulmonary aspergillus, galactomannan, Karius, SARS-CoV-2, fusarium, mucorales, mucor, rhizopus, scedosporium, fungal disease, invasive fungal disease, EORTC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A: fosmanogepix (APX001)
Arm Type
Experimental
Arm Title
Cohort B: fosmanogepix (APX001)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
fosmanogepix
Other Intervention Name(s)
APX001, E210
Intervention Description
IV and oral fosmanogepix
Primary Outcome Measure Information:
Title
Percentage of Participants Who Died After the First Dose of Study Drug Through Day 42
Description
Percentage of participants who died after first dose in the study through Day 42 were reported in this outcome measure. This outcome measure included all deaths from Day 1 through Day 42.
Time Frame
After first dose on Day 1 through Day 42
Secondary Outcome Measure Information:
Title
Percentage of Participants With Global Response Based on Data Review Committee (DRC) Assessment at End of Study Drug Treatment (EOST)
Description
Global response was classified as treatment success (complete or partial response [CR or PR]) or treatment failure (stable response [SR], progression of fungal disease [PD], or death) as determined by DRC. CR: survival within prespecified period of observation (PPOB), resolution of all attributable (att) symptoms and signs of disease and radiological (rad) abnormalities, and mycological (myco) evidence of eradication of disease. PR: survival within POB, improvement in att symptoms and signs of disease and rad abnormalities, and evidence of clearance of cultures or reduction of fungal burden. SR: survival within PPOB, minor or no improvement in fungal disease but no evidence of progression based on composite of clinical, rad and myco criteria, PD or death. PD: evidence of progressive fungal disease based on composite of clinical, rad and myco criteria. Death: death during PPOB, regardless of attribution. Data is presented for EOST which could have preceded Day 42 for some participants.
Time Frame
Any day from Day 1 until end of study treatment (any day up to Day 42)
Title
Percentage of Participants With Treatment Success or Treatment Failure for Global Response Based on Data Review Committee (DRC) Assessment at End of Study Drug Treatment (EOST)
Description
Global response was classified as treatment success (CR or PR) or treatment failure (SR, PD or death) as determined by DRC. CR: survival within prespecified POB, resolution of all attributable symptoms and signs of disease and rad abnormalities and myco evidence of eradication of disease. PR: survival within prespecified POB, improvement in attributable symptoms and signs of disease and rad abnormalities and evidence of clearance of cultures or reduction of fungal burden. SR: survival within prespecified POB, minor or no improvement in fungal disease, but no evidence of progression, based on composite of clinical, rad, and myco criteria, PD or death. PD: evidence of PD based on a composite of clinical, rad, and myco criteria. Death: death during prespecified period of evaluation, regardless of attribution. Percentage of participants with treatment success (CR, PR) and treatment failure (SR, PD, death) along with two-sided exact binomial 80% confidence interval is presented.
Time Frame
Any day from Day 1 until end of study treatment (any day up to Day 42)
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
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 4 weeks post last dose of study treatment that were absent before treatment or that worsened relative to pretreatment state. An SAE was any untoward medical occurrence that occurred, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; was a congenital anomaly/birth defect and other important medical events. AEs included SAEs and all non-SAEs.
Time Frame
Day 1 up to maximum of 31 days of follow up post last dose of study treatment, where maximum treatment duration was 42 days (maximum up to 73 days)
Title
Number of Participants With Clinically Significant Abnormality in Vital Signs
Description
Vital signs included body temperature, blood pressure, heart rate, respiratory rate, and oxygen saturation. Number of participants with clinically significant abnormality in vital signs as judged by investigator were reported in this outcome measure.
Time Frame
Day 1 up to maximum of 31 days of follow up post last dose of study treatment, where maximum treatment duration was 42 days (maximum up to 73 days)
Title
Number of Participants With Clinically Significant Abnormality in Laboratory Test Evaluations
Description
Clinical laboratory assessments included serum chemistry (bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, creatine kinase), hematology (including hemoglobin, hematocrit, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils and monocytes), coagulation (including Prothrombin time [PT]/ International normalized ratio [INR]), and urinalysis. Number of participants with clinically significant abnormality in any laboratory parameter as judged by investigator and reported as adverse events were presented.
Time Frame
Day 1 up to maximum of 31 days of follow up post last dose of study treatment, where maximum treatment duration was 42 days (maximum up to 73 days)
Title
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings
Description
ECG parameters included PR interval, QRS interval, QT interval, QT interval corrected using the Fridericia's formula (QTcF), QT interval corrected using the Bazett's formula (QTcB), RR interval and heart rate. Number of participants with clinically significant abnormal ECG findings as judged by investigator were presented.
Time Frame
Day 1 up to maximum of 31 days of follow up post last dose of study treatment, where maximum treatment duration was 42 days (maximum up to 73 days)
Title
Number of Participants With Clinically Significant Change From Baseline in Physical and Neurological Examinations
Description
Physical examination included an assessment of general appearance, skin, eyes, heart, chest, abdomen, and a neurological examination. Components of the neurological examination included cranial nerve, sensory, and motor examination; reflex and gait testing; and coordination assessment. Clinically significant changes were judged by investigator.
Time Frame
Day 1 up to maximum of 31 days of follow up post last dose of study treatment, where maximum treatment duration was 42 days (maximum up to 73 days)
Title
Plasma Concentrations of Fosmanogepix
Time Frame
Days 1, 2, 3, 4, 7: Pre-dose and 3 hours post-dose; Days 6, 13, 14: 3 hours post-dose, Day 15: pre-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males or females, 18 years or older.
Patients with proven or probable IMI caused by Aspergillus spp. Patients who present with IMI due to other filamentous fungi (eg, Scedosporium spp., Fusarium spp., and Mucorales fungi such as Mucor spp. or Rhizopus spp.) may also be enrolled.
Have limited or no treatment options due to documented or anticipated resistance, contraindication, intolerance, or lack of clinical response to SOC antifungal therapy, as advocated by the relevant regional/country treatment guidelines.
Patients where the Investigator considers that there is a potential advantage of using APX001 over current SOC (eg, broad spectrum of activity, emergence of IMI during antifungal prophylaxis, activity against resistant mold pathogens, IV and PO formulations, favorable DDI profile, favorable hepatic and renal safety profile, wide tissue distribution including brain), and/or where the SOC antifungal therapy carries significant risk of toxicity or treatment failure (eg, DDI risk, safety/toxicity risk, site of infection not accessible by SOC).
Exclusion Criteria:
Refractory hematologic malignancy.
Chronic aspergillosis, aspergilloma, or allergic bronchopulmonary aspergillosis.
Treatment with systemic (PO, IV, or inhaled) mold active antifungal therapy for 120 hours immediately before initial dosing. Note: patients with invasive fungal infection caused by a mold with documented resistance to or lack of coverage by the prior SOC in question, may have received >120 hours prior treatment and remain eligible for the study.
Evidence of significant hepatic dysfunction.
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
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
IP Address : City of Hope Investigational Drug Services (IDS)
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
Duke Department of Pharmacy/Investigational Drug Service (IDS)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Duke Medicine Pavilion
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Duke University Medical Center (Duke South Clinic)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Duke University Medical Center(Duke Hospital)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Cliniques Universitaires de Bruxelles Hôpital Erasme - Department of Infectious Diseases
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
UZ Leuven - Department of Haematology
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
CHU UCL Namur - Mont- Godinne University Hospital - Intensive Care Unit
City
Yvoir
ZIP/Postal Code
5530
Country
Belgium
Facility Name
Klinikum Neuperlach, Klinik fur Hamatologie und Onkologie
City
Munchen
State/Province
Bavaria
ZIP/Postal Code
81737
Country
Germany
Facility Name
Universitätsmedizin der Johannes Gutenberg-Universität Mainz III
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Pharmacy
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Pharmacy
City
Ramat-Gan
ZIP/Postal Code
5262160
Country
Israel
Facility Name
Sheba Medical Center, Tel Hashomer
City
Ramat-Gan
ZIP/Postal Code
5262160
Country
Israel
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 URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=APX001-202
Description
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Learn more about this trial
Open-label Study of APX001 for Treatment of Patients With Invasive Mold Infections Caused by Aspergillus or Rare Molds
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