Paediatric HIVDevelopment

 

  • Target disease: Paediatric HIV
  • Main partners (since project start): AbbVie, USA; Cipla Ltd., India; Department of Health, South Africa; Medical Research Council, UK; UNITAID; Clinton Health Access initiative (CHAI); Centre for Disease Control and Prevention (CDC)/President’s Emergency Plan for AIDS Relief, USA; Institute of Tropical Medicine, Antwerp; Médecins Sans Frontières; Necker Institute, France; various academic partners in South Africa, Kenya, Uganda, and Tanzania; WuXi AppTech, China.
  • Project start: 2012
  • Funding (since project start): French Development Agency (AFD), France; Médecins Sans Frontières/Doctors without Borders, International/Norway; Spanish Agency for International Development Cooperation (AECID), Spain; Swiss Agency for Development and Cooperation (SDC), Switzerland; UNITAID, Switzerland.

 

Overall Objective:

  • Following the work that led to the registration of a “2-in-1” lopinavir/ritonavir (LPV/r) fixed-dose combination, develop and register a solid, taste-masked, first-line LPV/r-based fixed-dose formulation with two nucleoside reverse transcriptase inhibitors (NRTIs), lamivudine and abacavir

 

 

The objective is to combine the four drugs needed for the treatment of paediatric HIV into an easy-to-use single unit, or fixed dose combination, which is heat-stable, taste-masked, solid, does not contain alcohol or inappropriate solvents.

 

A first-line “4-in-1” fixed-dose combination of abacavir/lamivudine/lopinavir/ritonavir (ABC/3TC/LPV/r) is on track to be submitted for registration in 2019. This 4-in-1 fixed-dose combination will be simple to use with water, milk, breast milk, and food. It will be taste-masked and heat-stable – a great improvement over the current option, a paediatric syrup of lopinavir/ritonavir (LPV/r) with high-alcohol content.

To provide clinical data in young HIV-infected infants and children, DNDi is preparing a study, called LOLIPOP, to assess this 4-in-1 combination as an easy-to-use paediatric formulation in a Phase I/II study. The LOLIPOP study, which has received ethical approval, will begin in March 2019 in Uganda and will generate pharmacokinetic, safety, and acceptability data on the 4-in-1 to provide evidence for worldwide scale-up.

Preliminary pharmacokinetic studies in healthy human volunteers were conducted in 2017 with a final 4-in-1 formulation. Bioequivalence studies in healthy human volunteers will be performed in 2018, enabling regulatory filing. Safety, acceptability, and efficacy data on this new formulation will also be generated in sub-Saharan Africa to provide evidence for worldwide scale-up. The objective is to submit the 4-in-1 dossier for registration in late 2018.

Following preliminary studies, the best formulation candidates in terms of bioavailability and taste-masking have been chosen – out of the 30 formulations evaluated since 2014 – for testing in healthy human volunteers in on-going Phase I studies.

Three of the most promising formulations tested in previous in vivo studies were assessed, and were found to be highly bioavailable in phase I studies in man. Additional bioavailability studies and standardized electric tongue taste testing (e-tongue) of granules with modified coatings and different polymers will be performed in 2016.


Last update: February 2019