Clinical trial NCT06925321: A Phase 3 Efficacy and Safety Study of Fosmanogepix for the Treatment of Adult Patients With Invasive Mold Infections.
Official title: An Interventional Phase 3, Open-label, Two-cohort Study to Investigate the Efficacy and Safety of Fosmanogepix in Adult Patients With Invasive Mold Infections Caused by Aspergillus Spp., Fusarium Spp., Lomentospora Prolificans, Mucorales Fungi, or Other Multidrug Resistant Molds
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Invasive Mold Infections
Keywords: Fungal infection
Antifungal
Mold infection
Rare molds
Multidrug resistant mold
Aspergillus spp.
Fusarium spp.
Lomentospora prolificans
Mucorales fungi
Scedosporium spp.
Lead sponsor: Basilea Pharmaceutica
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2025-04-13
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An open-label, 2-cohort study
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of fosmanogepix (administered IV or oral) for the treatment of adult patients with invasive mold infections. The study is looking for patients who have been diagnosed with invasive mold infections. The maximum study duration will be approximately 8 months, including a target study treatment duration of 84 days which can be extended up to 180 days and follow-up period.

The patient will be assigned to one of two treatment cohorts:

Cohort A (primary therapy): Patients will receive either the study drug or institutional standard of care antifungal treatment.

Cohort B (salvage treatment; i.e. treatment given after patients did not respond to previous treatments or did not tolerate them): Patients will receive the study drug

The primary aim is to compare the all cause mortality with a fixed threshold at Day 42.


Eligibility criteria: Main Inclusion Criteria:

1. Diagnosis of proven or probable Invasive mold infection (IMI) defined in accordance with the Revision and Update of the Consensus Definitions of Invasive Fungal Disease from the EORTC/MSGERC as adapted for this study and caused by Aspergillus spp. (in patients with limited treatment options), Fusarium spp., Lomentospora prolificans, Mucorales fungi, or other multi-drug resistant molds.
2. Patient's condition allows for appropriate infection source control measures.

Main Exclusion Critera:

1. Refractory hematologic malignancy.
2. Chronic aspergillosis, aspergilloma, or allergic bronchopulmonary aspergillosis.
3. COVID-19 associated mucormycosis.
4. Invasive fungal disease caused by more than one fungal pathogen is not permitted in Cohort A but is permitted in Cohort B.
5. Patients with a Karnofsky Performance Status \< 20 at Screening.
6. Requirement, or anticipated requirement, for hemodialysis, peritoneal dialysis, or hemofiltration.
7. Patients with known human immunodeficiency virus infection.
8. Ongoing neurological disorders.
9. Patients receiving hospice/comfort care only.
10. Other medical or psychiatric condition.
11. Current use of any prohibited concomitant medication(s).
12. Current/ previous administration of an investigational drug within 30 days.
13. Prior enrollment in this or any previous study of fosmanogepix.
14. Moderate or severe hepatic impairment.
15. Patient who is pregnant or lactating.
16. Known hypersensitivity to fosmanogepix, manogepix, or any of their excipients.

Primary outcomes:
measure: Day 42 all-cause mortality rate
timeFrame: Day 42
Secondary outcomes:
measure: Proportion of patients with overall response of treatment success
timeFrame: Day 42, Day 84 and up to 180 days
measure: Proportion of patients with clinical response of treatment success
timeFrame: Day 42, Day 84 and up to 180 days
measure: Proportion of patients with mycological response of eradication or presumed eradication
timeFrame: Day 42, Day 84 and up to 180 days
measure: Proportion of patients with radiological response of complete response or partial response
timeFrame: Day 42, Day 84 and up to 180 days
measure: All-cause mortality rate at Day 84
timeFrame: Day 84
measure: Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), treatment-related AEs, adverse events of special interest (AESI), and AEs leading to discontinuation
timeFrame: Screening up to follow-up 6 weeks after EOST (target duration approximately up to 8 months)
measure: Number of patients with clinically significant laboratory abnormalities
timeFrame: Up to follow-up 6 weeks after EOST (target duration approximately up to 8 months)
measure: Number of patients with abnormal neurological examination findings
timeFrame: Up to follow-up 6 weeks after EOST (target duration approximately up to 8 months)
measure: Assessment of 12-lead electrocardiogram corrected QT (Fridericia method) Interval (ECG QTcF Interval)
timeFrame: Up to follow-up 6 weeks after EOST (target duration approximately up to 8 months)
measure: Plasma concentrations versus time of fosmanogepix (prodrug) and manogepix (active moiety) following IV administration
timeFrame: Pre-dose, 3,6, and 9 hours post-start of the 3-hour IV infusion on Day 3, and at 24 hours (prior to Day 4 dosing)
measure: Plasma concentrations versus time of fosmanogepix (prodrug) and manogepix (active moiety) following oral administration
timeFrame: On days 7, 14, 28, and 42. Post-dose plasma samples will also be collected: 72 hrs and 192 hrs after last dose.
Other outcomes:
Locations:
Study officials:
affiliation: Basilea Pharmaceutica International Ltd, Allschwil
name: Daniel Ionescu, MD
role: STUDY_DIRECTOR
References: