Anakinra Pilot 2 - A Study to Optimise Dose and Route of Administration of Anakinra in Preterm Infants

Advances in neonatal intensive care have significantly improved the survival rates for extremely premature neonates. Despite this, many survivors develop chronic conditions such as cerebral palsy and chronic lung disease, primarily due to the pro-inflammatory environment common in these patients. Efforts to reduce these conditions using anti-inflammatory glucocorticoids are effective but are hindered by significant adverse effects that outweigh potential benefits for most neonates.

Crucially, not only is inflammation an important driver of morbidities of prematurity, but as shown by the investigators and other research groups, the potent pro-inflammatory cytokine interleukin-1 is a key player.

A phase I/IIa trial of anakinra in extremely premature infants (24 - 27+6 weeks gestational age) demonstrated feasibility of administration intravenous over the first 3 weeks of life, without any acute safety concerns and confirmation of mechanistic pharmacokinetic predictions.

The aims of this phase II dose-ranging trial (Anakinra Pilot 2, AP2) are to:

1. Establish pharmacokinetics, linearity and target concentration attainment over a range of doses, to determine optimal dosing regimen.
2. Assess feasibility and pharmacokinetics of an alternative route of administration (RoA), namely subcutaneous, in week 3 of treatment.
3. Further expand safety & feasibility, as well as perform exploratory pharmacometric dose-exposure-response analysis, against biomarkers and early efficacy endpoints.