HIV TREATMENT
2020
Action 27. Mobilize their networks and work with communities to help build treatment literacy, generate demand, and expand access to ARVs among children.
Action 34. Increase efforts to share information on the roll-out of new paediatric formulations, including lessons learned.
Paediatric HIV & TB : Rome Action Plan
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.
Commitment 12
October 2021
Key Treatment Studies
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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 (MOCHA (More Options for Children and Adolescents) Study
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Status: Enrollment is ongoing at sites in Africa, Asia and the US and expected to be completed in Q2/Q3 2022.
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IMPAACT 2036 - Phase I/II Study of the Safety, tolerability, Pharmacokinetics, 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 (CRAYON Study)
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Status: The protocol is in development and expected to be finalized in Q2/Q3 2022.
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IMPAACT 2022 (formerly CAP 534) - Feasibility and acceptability of long acting injectable (LAI) ARV medications in non-adherent HIV+youth
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Status: Development discontinued due to lack of pharmaceutical company support and no alternative source of study products.
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IMPAACT 2023 – A Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Dolutegravir in Neonates Exposed to HIV-1
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Status: The protocol is in the final stage of development and expected to be finalized in September 2021.
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IMPAACT 2029 – Phase I/II Study of Switching to Fixed Dose Combination Dolutegravir/Rilpivirine among Virologically Suppressed Children and Adolescents Living with HIV
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Status: The protocol is nearly final after modifications to limit enrollment to US sites, reflecting updated pharmaceutical company plans for commercialization.
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IMPAACT 2019 - Phase I/II Study of the Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in Children with HIV Less than 12 Years of Age
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Status: Enrollment is expected to be completed in September 2021.
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IMPAACT 2014 - Phase I/II Study of the Pharmacokinetics, Safety, and Tolerability of Doravirine (MK-1439) and Doravirine/Lamivudine/Tenofovir Disoproxil Fumarat (MK-1439A) in Children and Adolescents with HIV
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Status: Enrollment was completed in 2020; follow-up is ongoing and has recently been extended from anticipated completion of Q4 2021 to Q2 2022 to ensure post-trial access to study drugs.
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Commitment 13:
March 2022
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CRAYON (LA CAB/RIL) for younger children. Protocol under development, final version to be completed by 8/2022
Commitment 14:
March 2022
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PK/Safety of dispersible ABC/DTG/3TC in children 6-14kg presented at CROI 2022
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PK/Safety of LA CAB/Ril in Adolescents presented at CROI 2022
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
April 2021
IMPAACT study status
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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
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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
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Feasibility and acceptability of long acting injectable (LAI) ARV medications in non-adherent HIV+youth (CAP534)
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IMPAACT 2019 - Phase I/II study of PK, Safety of ABC/DTG/3TC in <12 years of age
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IMPAACT 2029 - Phase I/II study of switching to fixed dose combination dolutegravir/rilpivirine - Populations: virologically suppressed children and adolescents
Previous
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.
October 2020
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.
Previous
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.
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:
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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.
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Complete palatability and acceptability work on new formulations early on in the field, ideally in diverse populations.
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Ensure coinfected patients are included to explore drug-drug interactions.
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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:
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Initiate preparation for paediatric studies as soon as a given drug shows promising efficacy and safety in Phase IIa adult studies.
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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.
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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.
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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.
March 2022
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Protocol 2034 (TB alliance drug pretonamid) approved protocol under development
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Protocol 1108: new TB guidelines include dosing of bedaquiline in young kids derived from 1108
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Protocol 2024: INH/Rifapentine for 1 month - protocol near completion
October 2021
Key Tuberculosis Studies
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IMPAACT P1108 – Phase I/II, Open-Label, Single Arm Study to Evaluate the PK, Safety & Tolerability of Bedaquiline in Combination with Optimized Individualized MDR-TB Therapy in HIV-Infected & HIV-Uninfected Infants, Children & Adolescents with MDR-TB Disease
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Status: Enrollment is ongoing; data recently shared with WHO contributed to rapid communication on updated guidance on the management of tuberculosis in children and adolescents (https://www.who.int/publications/i/item/9789240033450)
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IMPAACT 2003B/A5300B - Protecting Households On Exposure to Newly Diagnosed Index Multidrug-Resistant TB Patients (PHOENIx MDR-TB)
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Status: Enrollment is ongoing in collaboration with the ACTG.
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IMPAACT 2037/HVTN 604 - Phase I/II Study of the Safety and Immunogenicity of VPM1002 Vaccination and BCG Re-Vaccination against Tuberculosis in South African Pre-Adolescents Living with and without HIV
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Status: The protocol is in development in collaboration with the HIV Vaccine Trials Network (HVTN) and expected to be completed in Q1 2022.
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IMPAACT 2034 - Phase I Study of the Pharmacokinetics, Safety, and Acceptability of Pretomanid in Children with Rifampicin-Resistant Tuberculosis
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Status: The protocol is in development in collaboration with the TB Alliance and expected to be completed in Q4 2021.
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IMPAACT 2024 - Phase I/II Dose Finding and Safety Study of Daily Rifapentine Combined with Isoniazid (1HP) for Tuberculosis Prevention in Infants, Children and Adolescents
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Status: The protocol is in development and expected to be completed in Q1 2022.
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IMPAACT 2005 - A Phase I/II Open-label, Single-Arm Study to Evaluate the PK, Safety, & Tolerability of Delamanid in Combination with OBR for MDR-TB in Children with MDR-TB with and without HIV
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Status: Enrollment is ongoing and expected to be completed in 2024.
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