Action 6: Prioritize PADO products in research and development plans.
Action 13: In pre-clinical and clinical development, initiate paediatric formulation development as soon as a given drug shows potential public health impact in adults, soon after Phase II trials are completed.
Action 14: Include adolescents when conducting initial adult efficacy trials, where possible and practical, or conduct parallel trials with the goal of providing information to support licencing for adolescents at the same time as adults.
Action 15: In the design of paediatric PK and safety studies, use weight-based dosing and enroll all children above 4 weeks concurrently, unless a strong rationale exists for not doing so.
Action 16: Assess acceptability and palatability of formulations for low-resource settings at early stages of the formulations development.
Action 17: Engage in early and regular consultations with the PAWG on PIP/PSPs, as well as recommended dosing and ratios for FDC development.
Action 18: Take all possible measures to rapidly complete development of priority paediatric drugs and formulations in the pipeline, with the goal of providing the maximum number of new formulations by end of 2018, especially for infants and young children.
Action 30: Strengthen and expand collaboration to overcome intellectual property challenges and otherwise facilitate technology transfer and knowledge sharing that can promote faster paediatric formulation development, including on challenges like taste-masking.
4. (individual commitment) Gilead committed to having clinical data ready for a low-dose TAF based regimen for children 2-12 years by late 2018/early 2019.
37. Prioritize development of low dose F/TAF dispersible tablet and complete investigation of low dose paediatric dose for 15-25kg by end of 2019.
38. Undertake a bioavailability study for dispersible tablets of F/TAF by mid-2019 and begin enrolment of children under 15kg by end 2019, using parallel enrolment of weight bands where feasible.
Commitments 37 and 38:
Bioavailability study on dispersible tablet should provide data to start enrollment children between 3 and 25kg, which will be divided into 4 WHO weight bands; parallel enrolment of different age groups will begin in early 2020. For low-dose tablet of FTC/TAF, there are 3 separate studies with NRTI backbone; 120/50mg tablet given to children between 14-25kg (around 60 children; will complete enrollment by the end of 2019); Plan to compile acceptability and palatability data from children in the study, particularly on the dispersible tablet and will be able to share that.
Study to support FTC/TAF for 14-<25 kg children ≥ 2 y of age – completed screening for all subjects in this cohort week of Sept 23 2019 [Wk 24 as primary endpoint for regulatory submission in Q3 2020][unboosted indication]. Regulatory filing expected in Q3 2020.
Clinical study to support FTC/TAF dispersible tablet – amendment in progress to be completed in Q1 2020. Will be enrolling as early as June/July 2020 in US and end of 2020 for other countries (Uganda, Zimbabwe, South Africa, Thailand), though could go into 2021 depending on the timelines for country approvals
BA study for dispersible tablet of FTC/TAF for < 14 kg completed in October 2019. Results showed that TAF was too low in this formulation. A second rBA/BE study on dispersible tablets with a couple of different FTAF ratios (each with increased TAF from our previous formulation) will be done in Aug 2020. Children will be enrolled by the summer of 2020.
April 2020: Gilead still intends to file for low dose TAF in children 14-<25 kg in the second half of this year. A second rBA study for dispersible F/TAF is still planned to occur in the early summer if the situation permits. F/TAF dispersible tablet data is still planned to come from the dispersible tablet of B/F/TAF which is planned to start enrollment by the end of the year (delayed due to country lockdowns). Enrollment of children into a pediatric study of the long-acting capsid inhibitor is planned for next year.
13. Share their methodological approaches to acceptability studies (including palatability and ease of administration) and contribute to a repository held by GAP-f partners to guide future investigation of acceptability for paediatric products.
14. Consider the use of the CRP for national registration of pediatric ARV products on PADO, Optimal formulary and Limited use lists.
15. Ensure all drug registration dossiers meet minimum requirements at the time of filing and that responses to specific queries are complete and provided in a timely manner
20. Manufacture new PADO priority pediatric ARV products “at risk” such that the new product is available for supply at time of approval/tentative approval/prequalification, including validation of manufacturing process during regulatory review.
Pharmaceutical companies, SRAs, WHO Prequalification Programme (PQ) and NRAs commit to:
1. Accelerate the national drug registration process to enable registration of any ARV listed by WHO EOI in around 40 participating countries within 1 year by ensuring that:
FOR PRODUCTS WITH PQ APPROVAL:
Company submits for registration in countries requesting use of the CRP (based on PQ approval) and process completed within around 4-5 months (country decisions within 3 months, plus submission processing time)
FOR PRODUCTS THAT HAVE NOT YET RECEIVED PQ APPROVAL:
Company submits with USFDA for full approval or tentative approval and process completed within 6 months;
USFDA approval or tentative approval review shared with WHO for Collaborative Registration
Procedure-lite (CRP-lite), a pilot program at first allowing FDA to share up to 5 minimally redacted reviews.
Company submits for registration in countries requesting use of the CRP (based on WHO PQ, FDA (CRP-lite) or other SRA review) and process completed in around 4-5 months (country decisions within 3 months, plus submission processing time)