The BENEFIT Kids Project: An update so far
The BENEFIT Kids Project, or Better Evidence and Formulations for Improved MDR-TB Treatment for Children, is a Unitaid-funded project aimed at contributing to reduced morbidity and mortality of children with MDR-TB through better access to improved prevention and treatment. The study, launched in 2019, has made remarkable progress, given the global challenges presented in 2020 due to the ongoing COVID-19 pandemic and related lockdown measures. The project, which aims to disseminate information designed to guide patients and providers, national authorities, and international bodies towards improved treatment for children with MDR-TB, has made great strides in all studies and received media coverage on multiple platforms.
During 2020, the study emblem (the dandelion) was designed to represent children’s innocence and freedom, while hinting at the movement of air, which can be challenging for many children who are affected by TB. During World TB Day in 2020, a video highlighting the scope of the BENEFIT Kids Project was released and shared on multiple platforms.
Further progress has been made in the first half of 2021 and all studies under the BENEFIT Kids umbrella have reached key milestones.
As part of Output 1, the aim is to provide improved evidence from existing data for better MDR-TB treatment for children through two systematic reviews of the MDR treatment literature in paediatrics and will feed into WHO guideline development. During 2020, the literature search for the review article on the pharmacokinetics and dosing of second-line TB drugs in children and adolescents was completed. Analyses has been postponed until after the WHO guideline discussions for the second review (see below).
For the second review on treatment outcomes, progress has been made on the literature search and the secondary analysis was initiated early 2021. Close collaboration with WHO has taken place in order to include the outcomes of the literature review in their 2021 guidelines on MDR treatment for children happening in mid-June 2021.
Output 2 of the project consists of five clinical trials to deliver improved evidence for better MDR-TB prevention and treatment for children:
-Trial 1 is called the “Delamanid Crush study”, which is led by TASK and assesses the relative bioavailability in adults of Delamanid dispersed in water compared to whole tablet form. In 2020 all approvals have been granted and the study opened to accrual in October. All study activities had been completed with the 24 participants in 2021 and by June, pharmacokinetic assay work and data analysis was underway. Study result dissemination is scheduled for the last quarter of 2021
-Trial 2 is the “PERFORM study” (Pharmacokinetics of lEvofloxacin FORmulations in children with MDR-TB exposure) and evaluates the pharmacokinetics and acceptability of 100 mg dispersible compared to 250 mg non-dispersible tablets of levofloxacin in children exposed to MDR-TB. During 2020, World Health Organisation Research Ethics Review Committee (WHO ERC) , Health Research Ethics Committee (HREC) and South African Health Products Regulatory Authority (SAHPRA) approvals have been granted. The first patient was screened in October 2020. By June 2021, recruitment is at target with half of the children required already enrolled. It is anticipated that study activities will be completed in the last quarter of 2021.
-Trial 3 is called the “CATALYST study” (Clofazimine and moxifloxacin PK, safety, and AccepTAbiLitY for paediatric TB treatment), and is a phase I/II trial of the pharmacokinetics, safety, tolerability, and acceptability of new formulations of clofazimine and moxifloxacin in children treated for rifampicin-resistant TB. This is a multi-site study which will recruit at the DTTC Brooklyn Chest Hospital (BCH) site as well as in India (partner BJMC and JHU, PI: Dr Aarti Kinikar) and the Philippines (De la Salle Medical Centre, PI: Dr Mel Frias) University. During 2020, the three sites prepared for opening of the study and the first three participant were enrolled early 2021 in South Africa. The team also collected qualitative data from the participants.
-The “TB CHAMP” trial is the first ever randomized phase III placebo-controlled trial to assess the efficacy of levofloxacin preventive therapy vs. placebo in child contacts of MRD- TB. As of the end of 2020, 801 of 1009 children had been screened and 633 enrolled in the study. Interim analysis took place in Quarter 3 of 2020 after 500 contacts had been followed up for at least 24 weeks. By May 2021, 709 children had been enrolled in the study.
-Trial 5 is the “PETITE study” (PharmacokinEtic and safeTy of the 4-In-1 granules inneonaTEs) which is led by neonatologist Adrie Bekker. This is an open label, single arm, two-stage trial to evaluate the single and multi-dose pharmacokinetics and safety of the abacavir/lamivudine/ lopinavir/ritonavir (30/15/40/10mg) (4-in-1) fixed-dose granule formulation in HIV-exposed neonates. This study opened to accrual in September 2020 and Cohort 1A and Cohort 1B (16 children in total) was completed. The interim analysis was completed, and protocol amendment is required before Cohort 2 commences.
Output 3 aims to produce targeted formulation development and market shaping to improve availability of child-friendly formulations of key second-line TB drugs and will be undertaken in partnership with TB Alliance. Some progress has been made with identifying potential manufacturers through a Request for Proposal (RFP) process.
-The BENEFIT Kids Project was also featured on multiple media platforms, including the Stellenbosch University website, newspapers, and radio broadcasts (see table below). In addition, in December 2020, Unitaid published an article on their website featuring interviews with DTTC team members Susan Purchase, Hazel Davids-Ruiters, Simphiwe Simelane, and Daphne Van Ster. The article highlighted the importance of the work being done as part of the TB CHAMP study.
Although 2020 has been a challenging year, the dedicated team as part of the BENEFIT Kids Project persevered and are on track to make real changes in the lives of children affected by MDR-TB.
In the media
Stellenbosch University. Research project bridges treatment gap for children with MDR-TB. 24 March 2020. Available online:
http://www.sun.ac.za/english/Lists/news/DispForm.aspx?ID=7224
Youtube. BENEFIT Kids: Research project bridges treatment gap for children with MDR-TB. 24 Mach 2020. Available online:
https://www.youtube.com/watch?v=0AvwN35R6qY
Daily Maverick. South Africa: TB in children: Important research being done in Cape Town. 25 March 2020. Available online:
Spotlight. TB in children: The amazing research being done in Cape Town – Kathryn Cleary interview with Anneke Hesseling and Megan Palmer. Available online:
Stellenbosch University website. PETITE study searches for best treatment options for newborns exposed to HIV (Featuring Adrie Bekker and the PETITE Study). 27 November 2020. Available online:
http://www.sun.ac.za/english/Lists/news/DispForm.aspx?ID=7848
Cape Argus. Excitement over HIV drugs for children (Featuring the PETITE Study). 9 December 2020.
Yiba.co.za. PETITE study searches for best treatment options for newborns exposed to HIV. 1 December 2020. Available online:
https://yiba.co.za/petite-study-searches-for-best-treatment-options-for-newborns-exposed-to-hiv/
Broadcast (Radio)
-Anneke Hesseling was interviewed on RSG at the Woordfees in Stellenbosch. Presenter: Suzanne Paxton. Producer: Marlinée Fouché. 9 March 2020.
-Smile FM. BENEFIT Kids Project: The University of Stellenbosch is leading a new R280 million… 4 March 2020.
Podcast:
talks@stellenboschuni. PODCAST: PETITE study searches for best treatment options for newborns exposed to HIV (Featuring the PETITE Study). 3 December 2020. Available online:
