Pharmacogenomics for Better Treatment of Fungal Infections Clinical Trial

NCT06510699 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: PRAGMATIC 02
• Study Type: interventional
• Target: 104
• Locations: 2 countries
• Sites: 7

Brief Summary

This project aims to address invasive fungal infections in patients, by precision dosing of voriconazole based on CYP2C19 genotype testing with Bayesian dose-forecasting dosing software to develop patient-centric and maximally effective dosing regimens. This study investigates if voriconazole increases the proportion of patients achieving therapeutic exposure at day 8 of dosing compared with standard care; and will assess factors that influence the implementation of genotype testing and dosing software in the healthcare system, including fidelity, feasibility, acceptability and cost-effectiveness. It will recruit at least 104 kids and adults in a parallel-group randomised clinical trial. A hybrid feasibility sub-study will assess the scalability of genotype-directed dosing to ensure sustainable integration of the interventions into the clinical workflow. A health economic sub-study will evaluate the costs, health outcomes and cost-effectiveness of genotype-directed testing compared to standard care.

Conditions

Fungal Infection; Haematological Malignancy; Blood Cancer; Infectious Disease

Keywords

infection; cancer; pharmacogenomic; genotype-based dosing; CYP2C19

Outcome Measures

Primary Outcomes (1)

• Therapeutic trough voriconazole concentration at Day 8

  Proportion of patients with measured therapeutic trough voriconazole concentration at Day 9 (+/- 1 day)

  Day 8

Secondary Outcomes (19)

• Simulated therapeutic trough voriconazole exposure at Day 8

  Day 8

• Measured therapeutic trough voriconazole exposure at Day 14.

  Day 14

• Simulated therapeutic trough voriconazole exposure at Day 14

  Day 14

• Measured therapeutic trough voriconazole exposure at both Days 8 and 14

  Days 8 and 14

• Simulated therapeutic trough voriconazole exposure at both Days 8 and 14

  Days 8 and 14

Study Arms (2)

Precision Care

EXPERIMENTAL

Voriconazole dosing will be initiated using current standard care dosing. Samples for TDM and genotype testing will be collected. Based on the results of these tests on Day 5, 8, 14, and up to day 30 ( ± 1 day) patients will be evaluated for dose adjustment using dosing software that includes patient data including TDM and genotype data.

Other: genotype-directed dosing with dosing software based on therapeutic drug monitoring

Standard Care

NO INTERVENTION

Current standard of care at trial-site institutions uses weight-based (mg/kg) initial dosing of voriconazole, with dose adjustment based on standard therapeutic drug monitoring (TDM) results of measured voriconazole concentrations and based on clinical judgement.

Interventions

genotype-directed dosing with dosing software based on therapeutic drug monitoring OTHER

Genotype-directed dosing with dosing software based on therapeutic drug monitoring

Also known as: genotype directed with dosing software

Precision Care

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 2 years.
• Written informed consent obtained.
• Decision to prescribe voriconazole.
• Admitted to a trial site, or sufficient outpatient follow-up appointments are feasible

You may not qualify if:

• Post-allogeneic haematopoietic stem cell transplant (HCT) patient, without access to pre HCT DNA
• Death is likely imminent within 7 days.
• Previously randomised to this trial

Sponsors & Collaborators

• The University of Queensland: lead
• University of Sydney: collaborator
• Western Sydney Local Health District: collaborator
• Sydney Children's Hospitals Network: collaborator
• Peter MacCallum Cancer Centre, Australia: collaborator
• University of Melbourne: collaborator
• Royal Adelaide Hospital: collaborator
• Pathology Queensland: collaborator
• Royal Brisbane and Women's Hospital: collaborator
• Lady Cilento Children's Hospital, Brisbane: collaborator
• Metro North Hospital and Health Service: collaborator
• Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium: collaborator

Study Sites (7)

Fred Hutchinson Cancer Centre

Seattle, Washington, 908109-1024, United States

RECRUITING

Sydney Children's Hospital Network

Sydney, New South Wales, 21452031, Australia

RECRUITING

Westmead Hospital

Sydney, New South Wales, 2145, Australia

RECRUITING

Royal Brisbane & Women's Hospital

Brisbane, Queensland, 4029, Australia

RECRUITING

Children's Hospital Queensland

South Brisbane, Queensland, 4029, Australia

RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3053, Australia

RECRUITING

MeSH Terms

Conditions

Mycoses; Hematologic Neoplasms; Communicable Diseases; Infections; Neoplasms

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Neoplasms by Site; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jason A Roberts, PhD

  The University of Queensland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jason A Roberts, PhD

CONTACT

+61 7 3346 5032; j.roberts2@uq.edu.au

Luminita Vlad

CONTACT

61 7 3346 5045; l.vlad@uq.edu.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: PRAGMATIC is a parallel-group randomised (1:1) clinical trial aiming to recruit at least 104 patients. A hybrid feasibility sub-study will assess the scalability of genotype directed dosing to ensure a sustainable integration of the interventions into the clinical workflow. A health economic sub-study will evaluate the costs, health outcomes and cost effectiveness of genotype-directed testing compared to standard care.

Study Record Dates

• First Submitted: July 14, 2024
• First Posted: July 19, 2024
• Study Start: April 14, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): March 26, 2027
• Last Updated: April 16, 2026

Record last verified: 2025-10

Locations

US (1); AU (6)