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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-06-27

Study Completion Date

2026-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

A phase 2 randomised, three-arm, parallel-group, dose-ranging trial to determine safety, efficacy and optimal dosing of intravenous anakinra in premature neonates, with subcutaneous pharmacokinetic sub-study.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Anakinra for Preterm Infants Pilot

NCT05280340

Prematurity; Extreme Inflammation

ACTIVE_NOT_RECRUITING PHASE1/PHASE2

Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS

NCT05267821

Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)

RECRUITING PHASE2/PHASE3

Non Inferiority KawasakI Trial With Anakinra

NCT06697431

Kawasaki Disease Anakinra

NOT_YET_RECRUITING PHASE4

ANAVEX2-73 Study in Pediatric Patients With Rett Syndrome

NCT04304482

Rett Syndrome

COMPLETED PHASE2/PHASE3

A Phase 2b Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study, Evaluating Efficacy and Safety of Allocetra-OTS in Patients With Severe or Critical COVID-19 With Associated Acute Respiratory Distress Syndrome (ARDS)

NCT04922957

Covid19

TERMINATED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

The primary outcome is to refine understanding of anakinra population pharmacokinetics in extremely premature neonates, and at 3 different dosing levels, to allow determination of optimal dose for population target concentration attainment in future trials.

In addition, the pharmacokinetics of subcutaneously administered anakinra in extremely premature neonates (from week 3) will be explored. Population pharmacokinetic model development and validation, for intravenous and subcutaneous anakinra in premature neonates over the first 3 weeks of life, to enable dose determination for target concentration attainment.

Model performance and validation will be based on metrics and graphics of model 'goodness-of-fit', precision of parameter estimates (relative standard error \& confidence intervals for CL, Vd and Ka) and predictive performance and robustness, per published (PMID: 27884052) and regulatory guidance (FDA guidance on Population Pharmacokinetics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/population-pharmacokinetics).

Population Pharmacokinetic (PK)/Pharmacodynamic (PD) Modeling will also enable exploratory investigation of the relationship between anakinra dose, concentration-time course in blood, and drug effects, both biomarkers of inflammation and clinical endpoints.

AP2 will recruit 24 infants born 24-28 weeks-GA, randomised to one of 3 dosing arms, 8 infants/arm, stratified to ensure balanced GA-distribution. Participants will otherwise receive standard care.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Premature Infants Very Premature Infants Inflammation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

AP2 is a randomised, three-arm, parallel-group, dose-ranging trial to determine safety, efficacy and optimal dosing of intravenous anakinra in premature neonates, with subcutaneous pharmacokinetic sub-study. Neonates will be randomly assigned to 1 of 3 dosing levels (8 per group), with half of each dosing level assigned to recieve subcutaneous dosing in week 3.

Population pharmacokinetic and physiology-based pharmacokinetic modelling will be employed to build on pharmacokinetic analysis from AP1, including multiple dose levels and subcutaneous dosing. Pooling of pharmacokinetic data from AP1 and AP2 (total n = 48) will enable establishment of a pharmacokinetic model, including key pharmacokinetic parameters clearance (CL), volume of distribution (VD), and absorption rate (Ka, subcutaneous) with sufficient precision (based on relative standard error) and model performance. In addition, PK will be linked through modelling with biomarkers and outcomes in expoloratory PKPD analysis.

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Intervention Type DRUG

Standard care plus Anakinra for 21 days

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Anakinra (Kineret®)

Standard care plus Anakinra for 21 days

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Born between 24+0 and 28+6 weeks of gestation

Exclusion Criteria

* Inability of the legal representatives to consent,
* Genetic syndromes,
* Severe cardiac anomalies,
* Substantial pre-/perinatal compromise,
* Congenital diaphragmatic hernia,
* Intrauterine stroke,
* Conditions that could confound trial results
* Imminent death or plan for comfort / palliative care
* Infants born outside the recruiting institutions

Minimum Eligible Age

24 Weeks

Maximum Eligible Age

29 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No