A Phase II Randomized Study to Evaluate Measures for Endpoint Derivation in Patients With Progressive or Refractory Disseminated Coccidioidomycosis (DCM ) Treated With Olorofim Plus Baseline SOC or Placebo Plus Baseline SOC

Official title

COCCIMETRICS: A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Measures for Endpoint Derivation in Patients With Progressive or Refractory Disseminated Coccidioidomycosis (DCM) Treated With Olorofim Plus Baseline Standard of Care (SOC) or With Placebo Plus Baseline SOC

Overview

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

• Drug Olorofim
  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)
• Drug Placebo
  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)

Primary outcome measures

• Change from baseline in VF-PRO Mobility domain score [Time frame: Day 168]
• Change from baseline in VF-PRO Daily Function domain score [Time frame: Day 168]

Secondary outcome measures (3)

• % of patients with a reduction in severity of at least one of their most bothersome baseline DCM-related symptoms [Time frame: Day 28, Day 56, Day 84, Day 112, Day 140, Day 168]
• To monitor incidence of Adverse Events in both treatment arms [Time frame: up to the Day 168 study visit and 4-week Follow-up (FU)]
• To monitor incidence of Serious Adverse Events in both treatment arms. [Time frame: up to the Day 168 study visit and 4-week Follow-up (FU)]

Eligibility criteria

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:

• Are receiving antiretroviral therapy AND
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Other

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07712484 · F901318/0037

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗