Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202405769820746 Date of Approval: 15/05/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title UNIVERSAL2: Pharmacokinetics safety and acceptability of DRV/r for children living with HIV
Official scientific title Pharmacokinetics, safety and acceptability of a solid paediatric fixed-dose combination of darunavir/ritonavir (DRV/r) 120/20 mg for children living with HIV
Brief summary describing the background and objectives of the trial In December 2019, the WHO-led Paediatric Antiretroviral Drug Optimization (PADO) group reviewed priorities for drug development for children. High on the priority list was a solid paediatric fixed dose combination (FDC) of darunavir and ritonavir (DRV/r 120mg/20mg) for treatment experienced children. DRV/r is a robust HIV protease inhibitor (PI) combination with a very high genetic barrier to resistance with proven excellent efficacy in second line for children aged over 3 years and over 14kg. Darunavir has to be given in combination with low doses of ritonavir (RTV). DRV/r is administered once-daily in children without prior protease inhibitor exposure or with no DRV related resistance mutations (RAMS), but twice daily for children with ≥1 mutation associated with resistance to DRV. The recommended dose for once- and twice-daily dosing in children 10-25 kg is currently based on the use of separate oral solutions or single tablets of DRV and RTV. The administration of the treatment is therefore complicated and constrained by the individual dosages of the formulations available and also requires access to ongoing supply of tablets/solutions in all needed dosage/formulation. The new DRV/r 120/20 mg FDC tablet will greatly simplify treatment, however, the dose and dosing ratio between DRV and RTV may differ to approved doses of DRV and RTV when administered as separate liquid or solid formulations in children. The newly developed DRV/r 120/20 mg tablets used according to the proposed once or twice a day dosing will be safe, achieve drug exposures associated with efficacious outcomes in children and will be well accepted by children and their caregivers. The aim of UNIVERSAL2 is to determine the correct dosage and to assess the safety and acceptability of the new drug for children living with HIV.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) UNIVERSAL2
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Treatment: Drugs
Anticipated trial start date 30/09/2024
Actual trial start date
Anticipated date of last follow up 31/03/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 50
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Single Group Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Darunavir and Ritonavir Depending on weight bands once daily or twice daily 15 months Initiation of DRV/r FDC (120/20mg) as part of antiretroviral therapy (ART) with an Optimized Background Therapy (OBT) 50
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Confirmed HIV-1 infection • Aged ≥ 3 years • With unsuppressed viral load (HIV-1 RNA viral load > 1000 c/mL) on ART-regimen and eligible to switch to new DRV/r 120/20 mg-based regimen per investigator’s judgement • Able to swallow the DRV/r 120/20 mg tablets • Willing to receive the DRV/r 120/20 mg tablets • Parents or guardians, and children where appropriate, willing and able to give informed consent and to adhere to the protocol • Cohort-specific inclusion criteria: o Cohort A:  Have 1 or 2 DRV resistance-associated mutations (RAMs)*  Weigh 10 to <25 kg at screening o Cohort B:  Have no DRV RAMs*  Weigh 10 to <20 kg at screening. *DRV RAMs: V11I, V32I, L33F, I47V, I50V, I54M, I54L, T74P, L76V, I84V and L89V • Presence of >2 darunavir RAMs* • Failure of protease genotypic resistance testing at baseline, except if treatment history indicates that darunavir RAMs are very unlikely • Resistance to all NRTI available in the country or impossibility to define an OBT • Intercurrent illness (enrolment can take place after the illness resolves) • Creatinine ≥ 1.8 Upper Limit of Normal (ULN) or ALT ≥ 5 ULN or (ALT ≥ 3 ULN and bilirubin ≥2 ULN) at screening • Severe hepatic impairment or unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) • History or presence of known allergy or other contraindication to DRV/r or their components • Concomitant medications that may interact with the current antiretroviral treatment, in particular TB drugs (i.e: rifampicin, rifabutin, rifapentine, …). Child: 6 Year-12 Year,Preschool Child: 2 Year-5 Year 3 Year(s) 15 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 30/04/2024 Centre Hospitalier National d Enfants Albert Royer
Ethics Committee Address
Street address City Postal code Country
Avenue Cheikh Anta Diop Dakar 25755 Senegal
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 30/04/2024 Centre Mere et Enfant de la Fondation Chantal Biya
Ethics Committee Address
Street address City Postal code Country
Rue Henri Dunan 1 Yaounde 3526 Cameroon
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 30/04/2024 UNCST
Ethics Committee Address
Street address City Postal code Country
Plot 6, Kimera Road, Ntinda Kampala 6884 Uganda
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 30/04/2024 Joint Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
15 Phillips Avenue Belgravia Harare A178 Zimbabwe
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome area under the concentration-time curve over the time interval from dosing to 12 hours (AUC0-12) (Cohort A) and from dosing to 24 hours (AUC0-24) (Cohort B) week 2
Primary Outcome maximum plasma concentration (Cmax) and 12 hours or 24 hours post dose concentrations (C12 or C24) Week 2
Primary Outcome Occurrence of the following events: • serious adverse events (SAEs); • adverse events (AEs) of Grade 3 or higher; • treatment related AEs; • AEs leading to treatment discontinuation or modification. throught the study
Secondary Outcome • Acceptability of DRV/r tablets (120/20mg) to children and caregivers assessed through questionnaires and direct observation. throught the study
Secondary Outcome Efficacy: • HIV-1 RNA <50 c/mL and <400 c/mL at week 24 • Occurrence of a new or recurrent WHO clinical stage 3 or 4 event • Change in CD4 cell count and percentage from baseline to week 24 week 24
Secondary Outcome Pharmacokinetics: • RTV PK parameters and DRV unbound concentrations Throught the study
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Centre Mere et Enfant de la Fondation Chantal Biya Rue Henri Dunan Yaounde 1 Yaounde Cameroon
Centre Hospitalier National Enfants Albert Royer Fann, 25755 Dakar Senegal
Baylor College of Medicine Children s Foundation Block 5 Mulago Hospital Kampala Uganda
Joint Clinical Research Centre P.o.Box 10005 Kampala Uganda
University of Zimbabwe Clinical Research Centre 2 Allan Wilson Avenue Harare Zimbabwe
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP2 Anna van Saksenlaan, 51 The Hague Netherlands
Inserm ANRS MIE 2 rue d Oradour sur Glane Paris France
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Fondazione Penta ETS Corso Stati Uniti 4 Padova 35127 Italy Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
INSERM SC10 US19 16, Avenue Paul Vaillant Couturier Paris France
AMS PHPT Research Collaboration 49 Chang Lor Rd Chang Mai Thailand
CONTACT PEOPLE
Role Name Email Phone Street address
Public Enquiries Alessandra Nardone alessandra.nardone@pentafoundation.org +390497169822 Corso Stati Uniti 4
City Postal code Country Position/Affiliation
Padova Italy Fondazione Penta ETS
Role Name Email Phone Street address
Principal Investigator Elizabeth Kaudha ekaudha@jcrc.org.ug +256417723000 Plot 101 Lubowa Estates
City Postal code Country Position/Affiliation
Kampala Uganda Joint Clinical Research Centre
Role Name Email Phone Street address
Scientific Enquiries Albert Faye albert.faye@aphp.fr +33140032000 48 Bd Serurier
City Postal code Country Position/Affiliation
Paris France Hopital Robert Debre and Universite Paris Cite
Role Name Email Phone Street address
Principal Investigator Francis Ateba atebfranc@gmail.com +237699011307 B P 3526
City Postal code Country Position/Affiliation
Yaounde Cameroon Centre Mere et Enfant de la Fondation Chantal Biya
Role Name Email Phone Street address
Principal Investigator Aminata Diack adiackmbaye@gmail.com +221338594747 Av Cheikh Anta Diop
City Postal code Country Position/Affiliation
Dakar Senegal Centre Hospitalier National d Enfants Albert Royer
Role Name Email Phone Street address
Principal Investigator Hilda Mujuru hmujuru@iwayafrica.co.zw +263772259666 2 Cnr Mazowe Street and Allan Wilson
City Postal code Country Position/Affiliation
Harare Zimbabwe University of Zimbabwe Clinical Research Centre
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Data obtained through this study may be provided to qualified researchers with academic interest in HIV. Data or samples shared will be coded. Approval of the request and execution of all applicable agreements (i.e. a data transfer agreement) are prerequisites to the sharing of data with the requesting party. Study Protocol Data requests can be submitted starting 9 months after article publication and the data will be made accessible for up to 24 months. Extensions will be considered on a case-by-case basis. Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information or to submit a request to alessandra.nardone@pentafoundation.org
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information