Blastomycosis, Coccidioidomycosis, Dimorphic Fungal Infection, Endemic Mycoses, Histoplasmosis
Conditions
Keywords
Dimorphic fungi, Endemic mycoses, Salvage therapy, Coccidioidomycosis, Antifungal therapy
Brief summary
This Phase II platform trial will evaluate the safety, tolerability, and effectiveness of investigational antifungal agents as salvage or consolidation therapy in adults with dimorphic fungal infections, including coccidioidomycosis, blastomycosis, and histoplasmosis. The study will enroll adults who are receiving active antifungal therapy and who have intolerance, failure, or unavailability of standard first-line consolidation therapy. The first investigational agent evaluated in the platform trial is oteseconazole. Participants will receive study drug and complete follow-up assessments for symptom status, functional status, adverse events, laboratory safety, study drug discontinuation, and quality of life. Participants will be followed during therapy and for up to 6 months after therapy.
Detailed description
Dimorphic fungal infections, including coccidioidomycosis, blastomycosis, and histoplasmosis, are commonly treated with azole antifungals such as itraconazole or fluconazole as consolidation therapy. However, some patients experience intolerance, treatment failure, drug interactions, toxicity, or lack of access to standard first-line consolidation therapy. For these patients, treatment options are limited. This study is an open-label, single-arm Phase II platform trial designed to evaluate investigational antifungal agents as salvage or consolidation therapy in adults with dimorphic fungal infections. The first investigational agent evaluated in this platform is oteseconazole. Eligible participants will be adults with coccidioidomycosis, blastomycosis, or histoplasmosis who are on active therapy, are expected to require at least 6 additional months of antifungal therapy, and have intolerance, failure, or unavailability of current first-line consolidation therapy. Participants will complete screening and informed consent through REDCap. Study drug will be mailed to participants by the central pharmacy after enrollment. Participants will complete monthly follow-up surveys assessing symptom status, functional status, quality of life, antifungal therapy changes, and treatment tolerance. Safety monitoring will include adverse event tracking, serious adverse event reporting, and laboratory assessments. Participants will be followed for up to 18 months, including the treatment period and 6 months of post-therapy follow-up.
Interventions
DRUGOteseconazole
Participants will receive oral oteseconazole 600 mg twice daily for 12 days, followed by 600 mg weekly. Total treatment duration depends on diagnosis: up to 52 weeks for coccidioidomycosis, 26 weeks for blastomycosis, and 26 weeks for histoplasmosis.
Sponsors
University of Minnesota
Centers for Disease Control and Prevention
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an open-label, single-arm Phase II platform trial evaluating investigational antifungal agents as salvage or consolidation therapy in adults with dimorphic fungal infections, including coccidioidomycosis, blastomycosis, and histoplasmosis, who are intolerant of, have failed, or cannot access standard first-line consolidation therapy. The first investigational agent evaluated in the platform is oteseconazole.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of coccidioidomycosis, blastomycosis, or histoplasmosis and on active therapy * Age 18 years or older * Anticipated need for at least 6 additional months of antifungal therapy at enrollment * Intolerance, failure, or unavailability of current first-line consolidation therapy
Exclusion criteria
* Currently hospitalized * Central nervous system involvement of coccidioidomycosis, blastomycosis, or histoplasmosis * Previous administration of or allergy to study drug * Any condition for which participation would not be in the best interest of the participant or that could limit protocol-specified assessments * Females of childbearing potential * Breast Cancer Resistance Protein substrate medication interaction that cannot be managed by switching medication, discontinuation, 50% dose reduction, or use of the lowest dose * Children * Pregnant women/persons * Fetuses * Neonates * Prisoners * Adults lacking capacity to consent or adults with diminished or fluctuating capacity to consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Symptom Status | Baseline through 12 months | Symptom status change over time will be assessed using a 10-point visual analogue scale queried monthly through follow-up surveys. |
| Change in Functional Status | Baseline through 12 months | Functional status change over time will be assessed using a 10-point visual analogue scale queried monthly through follow-up surveys. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Event Rate | Through 1 year | Serious adverse event rate will be assessed through 1 year, including events such as death, all-cause re-hospitalization, permanent neurologic deficit, and other serious adverse events. |
| Discontinuation of Study Drug Due to Therapeutic Failure | Through study drug treatment period, up to 12 months | The number of participants who discontinue study drug due to therapeutic failure with worsening clinical symptoms will be assessed. |
| Discontinuation of Study Drug Due to Adverse Events | Through study drug treatment period, up to 12 months | The number of participants who discontinue study drug due to adverse events will be assessed. |
| Study Drug Discontinuation, Dose Reduction, or Interruption Due to Toxicity or Intolerance | Through study drug treatment period, up to 12 months | The incidence of study drug discontinuation, dose reduction, or interruption due to toxicity or intolerance will be assessed by grade. |
| Incidence of Laboratory Adverse Events | Through study drug treatment period, up to 12 months | Laboratory adverse events will be assessed with focus on alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and direct, indirect, and total bilirubin, using the NIH DAIDS Adverse Event Grading document. |
| Change in PROMIS-29 Scores | Baseline through study follow-up, up to 18 months | PROMIS-29 scores will be assessed over time to evaluate changes in patient-reported health status and quality of life. |
| Change in Fatigue Symptom Status | Baseline through 12 months | Fatigue symptom status change over time will be assessed using a 10-point visual analogue scale queried monthly through follow-up surveys. |
Countries
United States
Contacts
CONTACTMatthew Pullen, MD
PRINCIPAL_INVESTIGATORMatthew Pullen, MD
University of Minnesota
Outcome results
None listed