Coccidioides Immitis Infection, Coccidioides Infection, Coccidioides Posadasii Infection, Coccidioidomycosis, Coccidioidomycosis Infection, Disseminated Fungal Infection, San Joaquin Valley Fever, Valley Fever
Conditions
Keywords
Cocci, Coccidioidomycosis, Disseminated coccidioidomycosis, Olorofim, Valley Fever, Patient-reported outcomes, Valley Fever Patient Reported Outcome, Symptom assessment, Endpoint development, Outcome measure validation, Quality of life, Fungal infection, Invasive fungal disease
Brief summary
The purpose of this study is to test measurement tools (questionnaire about symptoms and a questionnaire about quality of life) to assess usability in the assessment of treatment effectiveness for people with disseminated coccidioidomycosis (DCM).
Detailed description
Valley Fever (coccidioidomycosis) is a serious fungal infection that can cause long-lasting symptoms. Currently marketed antifungal drugs have limitations including limited dosage forms, drug-drug interactions (DDIs), and significant adverse reactions. Olorofim is an antifungal candidate with a novel mechanism of action offering activity against resistant organisms, differences in safety profile, along with oral route of administration, predictable and reliable pharmacokinetic (PK) profile and limited potential for DDIs. This study tests whether the Valley Fever-Patient Reported Outcome (VF-PRO) questionnaire can reliably measure symptom impacts and changes over time in patients with severe forms of the disease (disseminated coccidioidomycosis (DCM)). The study will also assess symptoms of DCM and their severity, and whether olorofim, is safe and can help people with DCM when given together with standard antifungal medications (also known as standard-of-care or SOC).
Interventions
DRUGOlorofim
Arm A: Oral olorofim loading dose: 5 tablets (150 mg) to be taken twice daily at a 12-hour (± 1 hour) interval on Day 1 followed by a maintenance dose of 3 tablets (90 mg) to be taken twice daily at 12-hour (± 1 hour) intervals from Day 2 until Day 168 (± 7 days)
DRUGPlacebo
Arm B: Oral olorofim-matched placebo loading dose: 5 tablets (150 mg) to be taken twice daily at a 12-hour (± 1 hour) interval on Day 1 followed by a maintenance dose of 3 tablets (90 mg) to be taken twice daily at 12-hour (± 1 hour) intervals from Day 2 until Day 168 (± 7 days)
Sponsors
F2G Ltd
IQVIA RDS Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female patients, English- or Spanish-speaking, aged ≥18 years and weighing ≥40 kg. * Patients with progressive or refractory disseminated coccidioidomycosis (DCM) involving extra-pulmonary sites with or without ongoing active disease in lungs. * Standard of Care therapy for DCM to date has included 2 different triazoles (with or without a course of intravenous amphotericin B).
Exclusion criteria
* Patients who are unconscious. * Women who are pregnant or breastfeeding. * Known history of allergy, hypersensitivity, or any serious reaction to any component of the study drug. * Patients with or planned placement of indwelling CNS devices. * Patients receiving intrathecal amphotericin B at the time of study enrolment. * Coccidioidomycosis limited to fibro-cavitary pulmonary disease. * All bothersome DCM-related symptoms at study entry are due to irreversible damage (e.g., neurologic deficits due to stroke). * Other than cutaneous fungal infections treated topically and Pneumocystis jirovecii infections, patients with a second fungal infection requiring systemic antifungal treatment or prophylaxis. * Patients with microbiological findings or other potential conditions that are temporally related and suggest a different than study indication etiology for the clinical features. * Patients living with Human immunodeficiency virus (HIV) unless for at least 6 months prior to enrollment: 1. Are receiving antiretroviral therapy AND 2. Have no evidence of current clinical progression resulting from HIV infection. * Patients who have received prior treatment with olorofim/F901318. * Patients receiving treatment limited to supportive care due to predicted short survival time. * Patients with a baseline prolongation of QT using Fridericia's Correction Formula (QTcF) ≥500 msec, or at high risk for QT/QTc prolongation. * Evidence of hepatic dysfunction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in VF-PRO Mobility domain score | Day 168 | Change from baseline in VF-PRO Mobility domain score at the Day 168 (Week 24) study visit. |
| Change from baseline in VF-PRO Daily Function domain score | Day 168 | Change from baseline in VF-PRO Daily Function domain score at the Day 168 (Week 24) study visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| % of patients with a reduction in severity of at least one of their most bothersome baseline DCM-related symptoms | Day 28, Day 56, Day 84, Day 112, Day 140, Day 168 | % of patients with a reduction in severity of at least one of their most bothersome baseline DCM-related symptoms, and no worsening of their other most bothersome baseline DCM-related symptoms, at the Day 28, Day 56, Day 84, Day 112, Day 140 and Day 168 (Weeks 4, 8, 12, 16, 20 and 24) study visits. |
| To monitor incidence of Adverse Events in both treatment arms | up to the Day 168 study visit and 4-week Follow-up (FU) | — |
| To monitor incidence of Serious Adverse Events in both treatment arms. | up to the Day 168 study visit and 4-week Follow-up (FU) | — |
Contacts
CONTACTAngela Wardman
CONTACTJulia Vassiliadou
PRINCIPAL_INVESTIGATORGeorge R. Thompson, MD
University of California, Davis, School of Medicine
Outcome results
None listed