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

NCT06574789 | Recruiting Phase 2 DMC

• 1 other identifier: 107507
• Study Type: interventional
• Target: 232
• Locations: 2 countries
• Sites: 7

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.

Conditions

Cytomegalovirus Viraemia

Outcome Measures

Primary Outcomes (1)

• The proportion of participants who achieve CMV virological clearance by 6 weeks

  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.

  42 days

Secondary Outcomes (7)

• The proportion of participants who achieve CMV virological clearance before 3-weeks

  21 days

• The proportion of participants who develop CMV disease by 6 weeks

  42 days

• Difference between treatment groups in All-cause mortality by 6 months

  6 months

• The proportion of participants who develop drug resistant CMV infection by 6 months

  6 months

• The proportion of participants with treatment-related adverse effects (AEs)

  42 days

Study Arms (2)

Control: standard dosing

ACTIVE COMPARATOR

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

Drug: Standard dosing of IV ganciclovir

Intervention: individualised dosing using a web app

ACTIVE COMPARATOR

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.

Drug: Personalised dosing of IV ganciclovir

Interventions

Standard dosing of IV ganciclovir DRUG

IV ganciclovir at standard dosing

Control: standard dosing

Personalised dosing of IV ganciclovir DRUG

IV ganciclovir at a personalised dosing calculated using a ganciclovir dosing web app

Intervention: individualised dosing using a web app

Eligibility Criteria

• Age: 1 Month - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• Detectable clinically significant CMV viraemia and treating clinician determines that antiviral therapy is indicated.
• Willing to partake in the trial
• Willing/able to attend all follow up visits and capable of completing all trial assessments.
• Legally acceptable parent/guardian capable of providing consent on the participant's behalf.
• Treating clinician agreeable to child being enrolled in the trial.

You may not qualify if:

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

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead

Study Sites (7)

Sydney Children's Hospital

Sydney, New South Wales, 2031, Australia

RECRUITING

The Children's Hospital at Westmead

Sydney, New South Wales, 2145, Australia

RECRUITING

Queensland Children's Hospital

Brisbane, Queensland, 4101, Australia

RECRUITING

The Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

RECRUITING

Monash Children's Hospital

Melbourne, Victoria, 3168, Australia

RECRUITING

Perth Children's Hospital

Perth, Western Australia, 6009, Australia

RECRUITING

Starship Children's Hospital

Auckland, North Island, 1023, New Zealand

RECRUITING

Related Publications (18)

• Heston SM, Young RR, Tanaka JS, Jenkins K, Vinesett R, Saccoccio FM, Martin PL, Chao NJ, Kelly MS. Risk Factors for CMV Viremia and Treatment-Associated Adverse Events Among Pediatric Hematopoietic Stem Cell Transplant Recipients. Open Forum Infect Dis. 2021 Dec 16;9(2):ofab639. doi: 10.1093/ofid/ofab639. eCollection 2022 Feb.

  PMID: 35111869 BACKGROUND

• Chan S, Godsell J, Horton M, Farchione A, Howson LJ, Margetts M, Jin C, Chatelier J, Yong M, Sasadeusz J, Douglass JA, Slade CA, Bryant VL. Case Report: Cytomegalovirus Disease Is an Under-Recognized Contributor to Morbidity and Mortality in Common Variable Immunodeficiency. Front Immunol. 2022 Feb 15;13:815193. doi: 10.3389/fimmu.2022.815193. eCollection 2022.

  PMID: 35242131 BACKGROUND

• El Haddad L, Ghantoji SS, Park AK, Batista MV, Schelfhout J, Hachem J, Lobo Y, Jiang Y, Rondon G, Champlin R, Chemaly RF. Clinical and economic burden of pre-emptive therapy of cytomegalovirus infection in hospitalized allogeneic hematopoietic cell transplant recipients. J Med Virol. 2020 Jan;92(1):86-95. doi: 10.1002/jmv.25574. Epub 2019 Sep 3.

  PMID: 31448830 BACKGROUND

• Singh N, Winston DJ, Razonable RR, Lyon GM, Silveira FP, Wagener MM, Limaye AP. Cost-effectiveness of Preemptive Therapy Versus Prophylaxis in a Randomized Clinical Trial for the Prevention of Cytomegalovirus Disease in Seronegative Liver Transplant Recipients With Seropositive Donors. Clin Infect Dis. 2021 Nov 2;73(9):e2739-e2745. doi: 10.1093/cid/ciaa1051.

  PMID: 32712663 BACKGROUND

• Tan SK, Waggoner JJ, Pinsky BA. Cytomegalovirus load at treatment initiation is predictive of time to resolution of viremia and duration of therapy in hematopoietic cell transplant recipients. J Clin Virol. 2015 Aug;69:179-83. doi: 10.1016/j.jcv.2015.06.006. Epub 2015 Jun 10.

  PMID: 26209403 BACKGROUND

• Rastogi S, Ricci A, Jin Z, Bhatia M, George D, Garvin JH, Hall M, Satwani P. Clinical and Economic Impact of Cytomegalovirus Infection among Children Undergoing Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2019 Jun;25(6):1253-1259. doi: 10.1016/j.bbmt.2018.11.028. Epub 2018 Nov 29.

  PMID: 30502538 BACKGROUND

• Camargo JF, Kimble E, Rosa R, Shimose LA, Bueno MX, Jeyakumar N, Morris MI, Abbo LM, Simkins J, Alencar MC, Benjamin C, Wieder E, Jimenez A, Beitinjaneh A, Goodman M, Byrnes JJ, Lekakis LJ, Pereira D, Komanduri KV. Impact of Cytomegalovirus Viral Load on Probability of Spontaneous Clearance and Response to Preemptive Therapy in Allogeneic Stem Cell Transplantation Recipients. Biol Blood Marrow Transplant. 2018 Apr;24(4):806-814. doi: 10.1016/j.bbmt.2017.11.038. Epub 2017 Dec 5.

  PMID: 29217388 BACKGROUND

• Acquier M, Taton B, Alain S, Garrigue I, Mary J, Pfirmann P, Visentin J, Hantz S, Merville P, Kaminski H, Couzi L. Cytomegalovirus DNAemia Requiring (Val)Ganciclovir Treatment for More Than 8 Weeks Is a Key Factor in the Development of Antiviral Drug Resistance. Open Forum Infect Dis. 2023 Jan 23;10(2):ofad018. doi: 10.1093/ofid/ofad018. eCollection 2023 Feb.

  PMID: 36817745 BACKGROUND

• Jang JE, Hyun SY, Kim YD, Yoon SH, Hwang DY, Kim SJ, Kim Y, Kim JS, Cheong JW, Min YH. Risk factors for progression from cytomegalovirus viremia to cytomegalovirus disease after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2012 Jun;18(6):881-6. doi: 10.1016/j.bbmt.2011.10.037. Epub 2011 Nov 4.

  PMID: 22062802 BACKGROUND

• Launay E, Theoret Y, Litalien C, Duval M, Alvarez F, Lapeyraque AL, Phan V, Larocque D, Poirier N, Lamarre V, Ovetchkine P. Pharmacokinetic profile of valganciclovir in pediatric transplant recipients. Pediatr Infect Dis J. 2012 Apr;31(4):405-7. doi: 10.1097/INF.0b013e3182463a19.

  PMID: 22198827 BACKGROUND

• Martson AG, Edwina AE, Kim HY, Knoester M, Touw DJ, Sturkenboom MGG, Alffenaar JC. Therapeutic Drug Monitoring of Ganciclovir: Where Are We? Ther Drug Monit. 2022 Feb 1;44(1):138-147. doi: 10.1097/FTD.0000000000000925.

  PMID: 34610621 BACKGROUND

• Franck B, Woillard JB, Theoret Y, Bittencourt H, Demers E, Briand A, Marquet P, Lapeyraque AL, Ovetchkine P, Autmizguine J. Population pharmacokinetics of ganciclovir and valganciclovir in paediatric solid organ and stem cell transplant recipients. Br J Clin Pharmacol. 2021 Aug;87(8):3105-3114. doi: 10.1111/bcp.14719. Epub 2021 Jan 19.

  PMID: 33373493 BACKGROUND

• Moretti S, Zikos P, Van Lint MT, Tedone E, Occhini D, Gualandi F, Lamparelli T, Mordini N, Berisso G, Bregante S, Bruno B, Bacigalupo A. Forscarnet vs ganciclovir for cytomegalovirus (CMV) antigenemia after allogeneic hemopoietic stem cell transplantation (HSCT): a randomised study. Bone Marrow Transplant. 1998 Jul;22(2):175-80. doi: 10.1038/sj.bmt.1701302.

  PMID: 9707026 BACKGROUND

• Al Yazidi LS, Mitchell R, Palasanthiran P, O'Brien TA, McMullan B. Management and prevention of cytomegalovirus infection in paediatric hematopoietic stem cell transplant (HSCT) recipients: A binational survey. Pediatr Transplant. 2019 Aug;23(5):e13458. doi: 10.1111/petr.13458. Epub 2019 May 12.

  PMID: 31081265 BACKGROUND

• Jorga K, Reigner B, Chavanne C, Alvaro G, Frey N. Pediatric Dosing of Ganciclovir and Valganciclovir: How Model-Based Simulations Can Prevent Underexposure and Potential Treatment Failure. CPT Pharmacometrics Syst Pharmacol. 2019 Mar;8(3):167-176. doi: 10.1002/psp4.12363. Epub 2018 Dec 18.

  PMID: 30354026 BACKGROUND

• Yong MK, Shigle TL, Kim YJ, Carpenter PA, Chemaly RF, Papanicolaou GA. American Society for Transplantation and Cellular Therapy Series: #4 - Cytomegalovirus treatment and management of resistant or refractory infections after hematopoietic cell transplantation. Transplant Cell Ther. 2021 Dec;27(12):957-967. doi: 10.1016/j.jtct.2021.09.010. Epub 2021 Sep 21.

  PMID: 34560310 BACKGROUND

• Xia W, Li HCW, Lam KWK, Chung OKJ, Song P, Chiu SY, Chan CG, Ho KY. The Impact of Hematologic Cancer and Its Treatment on Physical Activity Level and Quality of Life Among Children in Mainland China: A Descriptive Study. Cancer Nurs. 2019 Nov/Dec;42(6):492-500. doi: 10.1097/NCC.0000000000000661.

  PMID: 30433896 BACKGROUND

• Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, Domecq C, Greenblatt DJ. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981 Aug;30(2):239-45. doi: 10.1038/clpt.1981.154. No abstract available.

  PMID: 7249508 BACKGROUND

Related Links

• National Ethics Advisory Committee. 2019. National Ethical Standards for Health and Disability Research and Quality Improvement. Wellington: Ministry of Health

Study Officials

• Amanda Gwee

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alice Lei

CONTACT

+61 0433 903 448; alice.lei2@rch.org.au

Sharelle Joseland

CONTACT

+61 0410052823; sharelle.joseland2@rch.org.au

Study Design

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

Study Record Dates

• First Submitted: August 20, 2024
• First Posted: August 28, 2024
• Study Start: October 29, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 8, 2026

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 12 months following analysis and article publication, upon approval of the request
• Access Criteria: Researchers must be from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept MCRI's conditions for access

Locations

AU (6); NZ (1)