42. Incorporate the development of pediatric specimen banks/repositories into studies to support faster clinical trials of new TB diagnostics and ensure open access to academic groups and manufacturers.

43. Support pediatric sample repositories, including non-sputum less invasive samples, for more expeditious technical evaluations of new diagnostics and regulatory approval processes.

44. Incorporate the development of pediatric chest X-ray image libraries into studies to develop and support improved machine learning algorithms for computer-assisted X-ray interpretation and ensure open access to other research groups and manufacturers.

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34. Rapidly develop and implement research actions (including carrying out specific studies to generate high quality evidence for regulatory submissions and high quality pharmacovigilance studies where needed) in the framework of GAP-f to accelerate access to innovative, high quality, and affordable drugs for children worldwide.

35. Ensure appropriate evidence generation from ongoing DTG studies to enable ViiV regulatory submissions by end 2019.

Action 34

PENTA has been working very closely with CHAI, WHO, EGPAF and other within the GAPf framework. Plans for studies are ongoing on TAF/xTC/DTG  and DRV/r FDC.

Action 35

DTG safety and dosing trials; moving ahead well. Also moving ahead on a study for DTG in 0 to 4 weeks.

PENTA and IMPAACT completed a new modeling work which will inform the dosing estimates for the neonatal DTG protocol which is moving quickly in development.

June 2020

IMPAACT is developing study to determine dosing for DTG in neonates 0 to 4 weeks old; study launch awaits manufacture of new elixir formulation, anticipated in 4th quarter or 2020.

Action 5. Focus research efforts on optimal drugs and formulations as defined by PADO.

Action 19. Undertake studies that use weight-based dosing, enroll all paediatric weight-band groups concurrently irrespective of age, and maximize opportunities to accelerate enrollment of subjects.

Action 5

PENTA and IMPAACT research networks have disseminated the Rome Action Plan to their members which is being considered for planning of future research projects.

Action 19

IMPAACT and PENTA are continuing collaborative work on the P1093 and ODYSSEY studies to expedite the determination of appropriate dosing for DTG in children below 30 kg. Both studies are investigating WHO weight bands- based dosing.

Building on two ongoing clinical trials, performed mostly in Africa, ODYSSEY and CHAPAS-4, PENTA has initiated with the support of UNITAID & WHO sample collection, drug levels evaluations, and analyses to model DTG, TAF and FTC exposure in young children with HIV and assess the feasibility of a DTG/TAF/FTC fixed dose combination. A similar work has been initiated to support the use of DRV/r 120/20 once and twice a day for children in need for a second line regimen. In parallel, PENTA has developed the clinical research protocols necessary to assess the short- and longer-term safety (including pharmacovigilance), pharmacokinetics, and effectiveness of all components of these fixed dose combinations. This clinical research program recently received 5 years funding from the EDTCP and will start implementation early 2021. Notably, parallel to the modelling and clinical research work described above and in collaboration with PENTA, CHAI has mapped out the formulation development program that will allow generic manufacturers to produce the formulations to be assessed as well as the regulatory support necessary for accelerating approval, registration and access to these products. This program involves the originator companies that have developed the product, Gilead, Janssen and ViiV, for TAF/FTC, DRV and DTG, respectively

11. Focus research efforts and rapidly disseminate research findings on optimal drugs and regimens as defined by the PADO TB priorities list.

12. Optimize clinical research in line with PADO priorities, including:

  • Use state of the art population PK methods to design and analyze paediatric PK studies allowing for inclusion of clinically relevant factors such as age, weight, formulations, HIV, malnutrition, etc.

  • Complete palatability and acceptability work on new formulations early on in the field, ideally in diverse populations.

  • Ensure coinfected patients are included to explore drug-drug interactions.

  • Rapid dissemination of findings with WHO and key stakeholders to inform policy, practice, and field guides.

 

13. Use the following best practices for the design and implementation of research studies:

  • Initiate preparation for paediatric studies as soon as a given drug shows promising efficacy and safety in Phase IIa adult studies.

  • Always include adolescents when conducting initial adult efficacy trials, or conduct parallel trials with the goal of providing information to support licensing for adolescents at the same time as adults.

  • In the design of paediatric PK and safety studies, study weight-based dosing and enroll all children above 4 weeks of age concurrently (i.e no age de-escalation), unless a strong rationale exists for not doing so.

  • Assess acceptability and palatability of formulations, including for use in low-resource settings, at early stages of the formulation’s development.

 

14. Develop drug susceptibility testing (DST) and methods in parallel to new molecule development and make pure drug substance available for DST at the same time as the introduction of a new molecule.

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