Invasive Mold Infections
Conditions
Keywords
Fungal infection, Antifungal, Mold infection, Rare molds, Multidrug resistant mold, Aspergillus spp., Fusarium spp., Lomentospora prolificans, Mucorales fungi, Scedosporium spp.
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.
Interventions
DRUGFosmanogepix IV infusion
Fosmanogepix will be administered IV
DRUGStandard of care antifungal therapy
Standard of care antifungal therapy will be administered in accordance with their respective product labels and/or standard practice guidelines
DRUGFosmanogepix oral tablet
Fosmanogepix will be administered orally.
Sponsors
Basilea Pharmaceutica
Biomedical Advanced Research and Development Authority
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
An open-label, 2-cohort study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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. Coronavirus disease 2019 (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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Day 42 all-cause mortality rate | Day 42 |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of patients with overall response of treatment success | Day 42, Day 84 and up to 180 days |
| Proportion of patients with clinical response of treatment success | Day 42, Day 84 and up to 180 days |
| Proportion of patients with mycological response of eradication or presumed eradication | Day 42, Day 84 and up to 180 days |
| Proportion of patients with radiological response of complete response or partial response | Day 42, Day 84 and up to 180 days |
| All-cause mortality rate at Day 84 | Day 84 |
| 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 | Screening up to follow-up 6 weeks after EOST (target duration approximately up to 8 months) |
| Number of patients with clinically significant laboratory abnormalities | Up to follow-up 6 weeks after EOST (target duration approximately up to 8 months) |
| Number of patients with abnormal neurological examination findings | Up to follow-up 6 weeks after EOST (target duration approximately up to 8 months) |
| Assessment of 12-lead electrocardiogram corrected QT (Fridericia method) Interval (ECG QTcF Interval) | Up to follow-up 6 weeks after EOST (target duration approximately up to 8 months) |
| Plasma concentrations versus time of fosmanogepix (prodrug) and manogepix (active moiety) following IV administration | 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) |
| Plasma concentrations versus time of fosmanogepix (prodrug) and manogepix (active moiety) following oral administration | On days 7, 14, 28, and 42. Post-dose plasma samples will also be collected: 72 hrs and 192 hrs after last dose. |
Countries
Australia, Austria, Belgium, Brazil, Canada, France, Germany, Greece, Israel, Italy, Netherlands, Spain, Taiwan, Thailand, United States
Contacts
CONTACTAlison Kuchta, MD
CONTACTMarc Engelhardt, MD
STUDY_DIRECTORAlison Kuchta, MD
Basilea Pharmaceutica International Ltd, Allschwil
Outcome results
None listed