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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06574789




Registration number
NCT06574789
Ethics application status
Date submitted
20/08/2024
Date registered
28/08/2024
Date last updated
30/10/2024

Titles & IDs
Public title
Individualised Dose Optimisation of Ganciclovir in Immunocompromised Children Trial (ID-MAGIC)
Scientific title
Individualised Dose Optimisation of Ganciclovir in Immunocompromised Children Trial (ID-MAGIC)
Secondary ID [1] 0 0
107507
Universal Trial Number (UTN)
Trial acronym
ID-MAGIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cytomegalovirus Viraemia 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Standard dosing of IV ganciclovir
Treatment: Drugs - Personalised dosing of IV ganciclovir

Active comparator: Control: standard dosing - 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

Active comparator: Intervention: individualised dosing using a web app - 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.


Treatment: Drugs: Standard dosing of IV ganciclovir
IV ganciclovir at standard dosing

Treatment: Drugs: Personalised dosing of IV ganciclovir
IV ganciclovir at a personalised dosing calculated using a ganciclovir dosing web app
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The proportion of participants who achieve CMV virological clearance by 6 weeks
Timepoint [1] 0 0
42 days
Secondary outcome [1] 0 0
The proportion of participants who achieve CMV virological clearance before 3-weeks
Timepoint [1] 0 0
21 days
Secondary outcome [2] 0 0
The proportion of participants who develop CMV disease by 6 weeks
Timepoint [2] 0 0
42 days
Secondary outcome [3] 0 0
Difference between treatment groups in All-cause mortality by 6 months
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
The proportion of participants who develop drug resistant CMV infection by 6 months
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
The proportion of participants with treatment-related adverse effects (AEs)
Timepoint [5] 0 0
42 days
Secondary outcome [6] 0 0
Change in Quality of Life measured over 6 months using the EQ-5D-Y Questionnaire.
Timepoint [6] 0 0
7 days, 42 days, 180 days
Secondary outcome [7] 0 0
Difference between treatment groups in cost-effectiveness over the 6-month period following randomisation
Timepoint [7] 0 0
6 months

Eligibility
Key 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.
Minimum age
1 Month
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/10/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2028
Actual
Sample size
Target
232
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Sydney
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Sydney
Recruitment hospital [3] 0 0
Queensland Children's Hospital - Brisbane
Recruitment hospital [4] 0 0
The Royal Children's Hospital - Melbourne
Recruitment hospital [5] 0 0
Monash Children's Hospital - Melbourne
Recruitment hospital [6] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2031 - Sydney
Recruitment postcode(s) [2] 0 0
2145 - Sydney
Recruitment postcode(s) [3] 0 0
4101 - Brisbane
Recruitment postcode(s) [4] 0 0
3052 - Melbourne
Recruitment postcode(s) [5] 0 0
3168 - Melbourne
Recruitment postcode(s) [6] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
North Island

Funding & Sponsors
Primary sponsor type
Other
Name
Murdoch Childrens Research Institute
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT06574789
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Amanda Gwee
Address 0 0
Murdoch Children's Research Institute
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Alice Lei
Address 0 0
Country 0 0
Phone 0 0
+61 0433 903 448
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06574789