Individualised Dose Optimisation of Ganciclovir in Immunocompromised Children Trial (ID-MAGIC)

Phase 2

Recruiting

• Conditions: Cytomegalovirus Viraemia
• Interventions: Drug: Standard dosing of IV ganciclovir; Drug: Personalised dosing of IV ganciclovir

• Registration Number: NCT06574789
• Lead Sponsor: Murdoch Childrens Research Institute

Brief Summary

This study is being conducted at seven major children's hospitals in Australia and New Zealand to test a new approach for treating a virus, called cytomegalovirus in children with weakened immune systems. The researchers want to find out if using a web app to customise the dose of a medication called ganciclovir is better at clearing the virus over a six-week period compared to the standard method of giving the medication.

Detailed Description

Immunocompromised children between 1 months to 18 years with cytomegalovirus viraemia who are admitted to one of the participating sites will be enrolled into the trial if eligible (see eligibility criteria) and randomly allocated into two groups. Children in the 'control- standard dosing group' will receive standard intravenous ganciclovir treatment for cytomegalovirus viraemia at a standard dosing of at 5mg/kg IV BD. Children in the "intervention: individualised dosing using a web app group" will receive a personalised intravenous ganciclovir dose calculated using an individualised IV ganciclovir dosing app. This approach considers the patient's weight, creatinine level, and target drug exposure, allowing for tailored dosing based on individual pharmacokinetic parameters. The virological clearance by 6 weeks of the children in each of the two groups will be compared.

Study Timeline

• Study First Submitted: 2024-08-20
• Study First Submitted QC: 2024-08-26
• Study First Posted: 2024-08-28
• Study Start: 2024-10-29
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-14
• Last Update Posted: 2025-01-16
• Primary Completion: 2028-06
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 232

Inclusion Criteria

1. Immunocompromised patients including transplant recipients (haematopoietic stem cell transplant (HSCT), solid organ transplant (SOT)), those receiving chemotherapy or other immunosuppression or those with a known/suspected inborn error of immunity (determined by an immunologist); and
2. Detectable clinically significant CMV viraemia and treating clinician determines that antiviral therapy is indicated.
3. Willing to partake in the trial
4. Willing/able to attend all follow up visits and capable of completing all trial assessments.
5. Legally acceptable parent/guardian capable of providing consent on the participant's behalf.
6. Treating clinician agreeable to child being enrolled in the trial.

Exclusion Criteria

1. Current or prior CMV infection with documented genotypic resistance to GCV (UL97 and/or UL54); or
2. Severe renal impairment (defined as estimated glomerular filtration rate (eGFR) <25mL/min); or
3. Congenital CMV infection; or
4. Life expectancy of less than 7 days as determined by the treating physician; or
5. History of allergy, or adverse reaction to GCV, aciclovir or any component of the formulation; or
6. Treating clinician determines that combination antiviral therapy is indicated for CMV infection; or
7. Has received >3 days of IV GCV or foscarnet or oral valganciclovir for the treatment of CMV infection prior to enrolment; or
8. Prior enrolment in the trial; or
9. Current recipient of another investigational product used for the treatment of CMV infection, as part of a clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control: standard dosing	Standard dosing of IV ganciclovir	Enrolled participant will receive standard dosing of IV Ganciclovir dependent on renal function: * CrCl \>/= 70mL/min: 5 mg/kg IV 12 hourly * CrCl \>/= 50-69: 2.5 mg/kg/ IV 12 hourly * CrCl \>/= 25-49: 2.5 mg/kg IV 24 hourly
Intervention: individualised dosing using a web app	Personalised dosing of IV ganciclovir	Enrolled participant will receive a personalised dosing of IV Ganciclovir calculated using an individualised IV ganciclovir dosing app, that considers the patient's weight, creatinine level, and at a target drug exposure (AUC24 between 40-100 mg.h/L), allowing for tailored dosing based on individual pharmacokinetic parameters.

Primary Outcome Measures

Name	Time	Method
The proportion of participants who achieve CMV virological clearance by 6 weeks	42 days	CMV virological clearance by 6 weeks to be compared between the two treatment groups. \* Virological clearance defined as two consecutives negative CMV polymerase chain reaction results, or detectable but CMV viral load is less than the lower limit of detection. Separated by at least 72 hours by 6-weeks (42 days) after randomisation.

Secondary Outcome Measures

Name	Time	Method
The proportion of participants who achieve CMV virological clearance before 3-weeks	21 days	The proportion of children who achieve virological clearance before 3-weeks (21 days) to be compared between the two treatment arms. Virological clearance defined as two consecutives negative CMV polymerase chain reaction results, or detectable but CMV viral load is less than the lower limit of detection. Separated by at least 72 hours.
The proportion of participants who develop CMV disease by 6 weeks	42 days	The proportion of children who develop CMV disease by 6 weeks to be compared between the two treatment groups. CMV disease assessed by the treating clinician based on signs/symptoms of disease followed by microbiological confirmation at the 6-week assessment.
Difference between treatment groups in All-cause mortality by 6 months	6 months	All-cause mortality by 6 months to be compared between the two treatment groups. All-cause mortality assessed by chart ± telephone review by the research team at 6-month timepoint.
The proportion of participants who develop drug resistant CMV infection by 6 months	6 months	The proportion of children who develop drug resistant CMV infection by 6 months to be compared between the two treatment groups. Children with refractory or further CMV infections following resolution of the initial infection will be evaluated for CMV-resistance through gene testing (UL97 and UL54).
The proportion of participants with treatment-related adverse effects (AEs)	42 days	The proportion of children with any treatment-related AEs to be compared between the two treatment groups. Assessed at end of treatment or at 6 weeks (whichever is later) by the treating team.
Change in Quality of Life measured over 6 months using the EQ-5D-Y Questionnaire.	7 days, 42 days, 180 days	Quality of Life (QoL) over the 6-month period following randomisation to be compared between the two treatment groups using the QoL EQ-5D-Y questionnaire, assessed at 7 days, 42 days and 180 days.; The EQ-5D-Y descriptive system comprises the following five dimensions: mobility, looking after oneself, doing usual activities, having pain or discomfort and feeling worried, sad or unhappy. Each dimension has 3 levels: no problems, some problems and a lot of problems.; The final question measures how good or bad the participants' health is that day on a scale from 0 to 100. 100 means the best health they can imagine and 0 means the worst health they can imagine.
Difference between treatment groups in cost-effectiveness over the 6-month period following randomisation	6 months	The total sum of all hospital and patient/family resources required per patient over the 6-month period to be compared between the two treatment groups.

Trial Locations

Locations (7)

Sydney Children's Hospital; 🇦🇺 Sydney, New South Wales, Australia

The Royal Children's Hospital; 🇦🇺 Melbourne, Victoria, Australia

The Children's Hospital at Westmead; 🇦🇺 Sydney, New South Wales, Australia

Queensland Children's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Monash Children's Hospital; 🇦🇺 Melbourne, Victoria, Australia

Perth Children's Hospital; 🇦🇺 Perth, Western Australia, Australia

Starship Children's Hospital; 🇳🇿 Auckland, North Island, New Zealand