Open-label Study of APX001 for Treatment of Patients With Invasive Mold Infections Caused by Aspergillus or Rare Molds

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04240886

Acronym

AEGIS

Enrollment

Registered

2020-01-27

Start date

2020-01-04

Completion date

2022-05-09

Last updated

2025-09-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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).

Interventions

DRUGfosmanogepix

IV and oral fosmanogepix

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Died After the First Dose of Study Drug Through Day 42	After first dose on Day 1 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

Measure	Time frame	Description
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)	Any day from Day 1 until end of study treatment (any day up to Day 42)	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)	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)	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	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)	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.
Percentage of Participants With Global Response Based on Data Review Committee (DRC) Assessment at End of Study Drug Treatment (EOST)	Any day from Day 1 until end of study treatment (any day up to Day 42)	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.
Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings	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)	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	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)	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	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	—
Number of Participants With Clinically Significant Abnormality in Laboratory Test Evaluations	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)	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.

Countries

Belgium, Germany, Israel, United States

Participant flow

Recruitment details

Study was planned to be conducted in two parallel cohorts: Cohort A included participants with invasive mold infections (IMA) and an exploratory Cohort B was planned to include participants with invasive aspergillus, who had COVID-19 or Influenza A/B. The study was terminated early and no participants were enrolled in Cohort B; hence data is not reported for Cohort B in any section.

Participants by arm

Arm	Count
APX001 (Fosmanogepix): Cohort A Eligible participants aged 18 years or older with invasive mold infections (IMI) and limited antifungal treatment options were included in this arm. On Day 1, participants received APX001 1000 milligram (mg) as a loading dose over 3 hours by intravenous (IV) infusion twice daily (BID). On Days 2 and 3, participants received APX001 600 mg as maintenance dose over 3 hours by IV infusion once daily (QD). From Day 4 till end of study treatment, for maintenance dose participants received either APX001 600 mg IV infusion QD over 3 hours or switched to APX001 800 mg orally QD on investigator discretion. Total treatment duration was maximum of 42 days. Participants had a follow-up visit at 4 weeks after last dose of study treatment and a follow-up telephone call was required on Day 84.	21
Total	21

Arm

Count

APX001 (Fosmanogepix): Cohort A

Eligible participants aged 18 years or older with invasive mold infections (IMI) and limited antifungal treatment options were included in this arm. On Day 1, participants received APX001 1000 milligram (mg) as a loading dose over 3 hours by intravenous (IV) infusion twice daily (BID). On Days 2 and 3, participants received APX001 600 mg as maintenance dose over 3 hours by IV infusion once daily (QD). From Day 4 till end of study treatment, for maintenance dose participants received either APX001 600 mg IV infusion QD over 3 hours or switched to APX001 800 mg orally QD on investigator discretion. Total treatment duration was maximum of 42 days. Participants had a follow-up visit at 4 weeks after last dose of study treatment and a follow-up telephone call was required on Day 84.

Total

Withdrawals & dropouts

Period	Reason	FG000
Follow-up Phase	Death	2
Follow-up Phase	Discontinuation by Subject	1
Follow-up Phase	Withdrawal by Subject	1
Treatment Phase	Adverse Event	5
Treatment Phase	Death	4
Treatment Phase	Discontinuation by Subject	1

Baseline characteristics

Characteristic	APX001 (Fosmanogepix): Cohort A
Age, Continuous	62.38 Years STANDARD_DEVIATION 11.71
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 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	1 Participants
Race (NIH/OMB) White	20 Participants
Sex: Female, Male Female	2 Participants
Sex: Female, Male Male	19 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	9 / 21
other Total, other adverse events	21 / 21
serious Total, serious adverse events	13 / 21

Outcome results

Primary

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.

Time frame: After first dose on Day 1 through Day 42

Population: The modified Intent-to-Treat (mITT) population included all participants who entered in the study, received at least 1 dose of study drug, and had a diagnosis of proven or probable IMI confirmed by the DRC.

Arm	Measure	Value (NUMBER)
APX001 (Fosmanogepix): Cohort A	Percentage of Participants Who Died After the First Dose of Study Drug Through Day 42	25.0 Percentage of participants

Secondary

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.

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)