12. A scientific agenda that focuses on PADO priorities and to undertake studies employing best practices to rapidly determine safety and dosing for new agents for infants, children, and adolescents.
13. Determine dosing and safety of DTG in newborns as well as in pediatric specific fixed dose combinations.
14. Determine safety, dosing, and acceptability of long-acting injectable ART with cabotegravir and rilpivirine in adolescents and children.
15. Accelerate work on its commitments despite the challenges posed by the COVID pandemic to ensure that optimal products are available to this vulnerable without added delay.
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.
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.
IMPAACT study status
MOCHA (More Options for Children and Adolescents) - IMPAACT 2017 - Phase I/II, multi-center, open-label, non-comparative study to confirm the dose and evaluate the safety, tolerability, acceptability - Populations: Virologically suppressed, aged 12 to <18 years and weighing >35 kgs
CREME (CS5024) - Phase I/II Study of the Safety, tolerability, Phamaracokinetics, and antiviral activity of Oral and Long-Acting Injectable Cabotegravir and Rilpivirine - Populations: Virologically suppressed, aged >2 to >12 years and weighing >10kgs and <50 kgs
Feasibility and acceptability of long acting injectable (LAI) ARV medications in non-adherent HIV+youth (CAP534)
IMPAACT 2019 - Phase I/II study of PK, Safety of ABC/DTG/3TC in <12 years of age
IMPAACT 2029 - Phase I/II study of switching to fixed dose combination dolutegravir/rilpivirine - Populations: virologically suppressed children and adolescents
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.
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.
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.
Phase I/II Study of the Safety and Pharmacokinetics of Oral and Long-acting Injectable Cabotegravir and Rilpivirine in Virologically Suppressed HIV‐Infected Adolescents has been modified to a q8 weeks dosing schedule and will now include international sites. In addition, a protocol to study pharmacokinetics and safety of Long acting Cabotegravir in children 2-12 years of age is in development.
PENTA and IMPAACT research networks have disseminated the Rome Action Plan to their members which is being considered for planning of future research projects.
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.
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.