Independent Safety Monitoring Board assessment enables recruitment of 2-5 year olds into OZ439/PQP Phase IIb trial

Combination could be the long-sought single-dose cure for malaria

20 Jan 2015

An Independent Safety Monitoring Board (ISMB) has recommended that recruitment of patients aged 2-5 years can begin for the ongoing Phase IIb safety and efficacy trial of a single dose of the antimalarial combination therapy OZ439 (artefenomel, a novel aromatic trioxolane)/piperaquine phosphate (PQP). The ISMB based this decision on assessment of safety data from over 80 patients, deeming it well-tolerated in patients above 5 years.

The main goal of the trial is to identify the optimal dose of OZ439/PQP. The ISMB’s decision will now enable the correct dosage to be validated in the paediatric population, an important step given that the overwhelming burden of malaria is borne by children under 5 years of age.

If the programme is successful and the combination approved, it would add to the arsenal of malaria medicines. A single-dose treatment would help to improve patient compliance compared to current 3-day therapies.

The Phase IIb trial of OZ439/PQP began in July 2014 and will continue over the course of 2015 in eight countries: Benin, Burkina Faso, Colombia, DRC, Gabon, Mozambique, Uganda and Vietnam. Designed to deliver safety and efficacy data in young children as quickly as possible, the trial adopted a staggered approach, treating adults first, then, as sufficient safety data was obtained, extending to 5-15 year olds.

As of today (January 20th), 95 of the 495 patients required for the trial have been treated with the combination. Following the ISMB’s recommendation, the treatment can now also be offered to 2-5 year olds (among the primary target population for this medicine). If the ISMB then deems it to be well-tolerated in this younger and more vulnerable group, the treatment can then be offered to infants aged 6 months to 2 years, the final age group in this trial, (also among the primary target population for this medicine).

“The safety data for this innovative combination antimalarial has been assessed in more than 60 adults and 20 children aged over 5 years,” said Prof. Dr Michael Ramharter, Coordinating Principal Investigator of the trial from the Medical University of Vienna and Albert Schweitzer Hospital, Lambaréné, Gabon where the first patient in this trial was enrolled. “The ISMB’s recommendation after review of this data means that we can now enrol and treat children of 5 years and under in the efficacy study. This is a significant milestone, as we move closer to developing a potential single-dose cure that can not only be used by adults but also by young children, the population hardest hit by malaria.”

"A single-dose cure would improve patient compliance considerably and would be a huge step forward for malaria treatment and its ultimate eradication," said Prof. Dr Peter Kremsner, Director of the Institute for Tropical Medicine at the University of Tübingen, Germany and Scientific Director of the Albert Schweitzer Hospital in Gabon. "That's why testing a combination of the promising new compound, OZ439, with a known partner drug in a single-dose cure is so important. Medicines for Malaria Venture is dedicated to the eradication of this terrible disease and it’s a privilege to work with them on this study."

“This trial is a key milestone in the development of OZ439,” said Dr David Reddy, MMV’s CEO.“Children below the age of 5 are the most vulnerable to malaria and the ISMB’s confirmation that OZ439 is sufficiently well-tolerated to be offered to this young population in a study setting is a vital step towards developing a new cure appropriate for young children. This medicine could be a game changer for malaria case-management, as it also has the potential to be the long sought-after single-dose cure. The fact that almost 100 patients required in the trial have been dosed with this new combination is real credit to our partners. I applaud each of the 10 trial sites – it is their commitment and collaboration that has enabled us to achieve this milestone.”