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

NCT07254000 | Recruiting Phase 2 DMC

• 1 other identifier: RES 24-0000-885A
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Premature Infants; Very Premature Infants; Inflammation

Keywords

anakinra; bronchopulmonary dysplasia; diffuse white matter injury; very premature infants

Outcome Measures

Primary Outcomes (3)

• Population Pharmacokinetics (PopPK) Model of the Clearance of anakinra in extremely premature neonates from birth, during the 3-week treatment period.

  Point Estimate of Population Total Clearance (CL) of anakinra will be reported.

  From Baseline up to Day 21

• Population Pharmacokinetics (PopPK) Model of the Volume of Distribution of anakinra in extremely premature neonates from birth, during the 3-week treatment period.

  Point Estimate of Population Volume of Distribution (VD) of anakinra will be reported.

  From Baseline up to Day 21

• Population Pharmacokinetics (PopPK) Model of the Absorption of Population of subcutaneously administered anakinra in extremely premature neonates from birth, during the 3-week treatment period.

  Point Estimate of Population Absorption of subcutaneously administered anakinra will be reported.

  Day 14-21

Secondary Outcomes (10)

• Incidence of bronchopulmonary dysplasia

  4 months.

• Hammersmith infant neurological examination

  6 months

• Incidence of intracranial/intraventricular haemorrhage and peri-ventricular leukomalacia.

  4 months

• Safety of anakinra in extremely premature neonates.

  4 weeks

• Individual Total Clearance (CL) of anakinra in extremely premature neonates.

  From Baseline up to Day 21.

Other Outcomes (5)

• Feasibility of 3 weeks of anakinra administration to extremely premature neonates from birth, both intravenously and subcutaneously.

  1 month

• Influence of anakinra on microbiome.

  3 weeks

• Pharmacokinetic (PK)/Pharmacodynamic (PD) Model of the Effect of anakinra Systemic Exposure on clinical endpoints.

  4 months

Study Arms (6)

Anakinra dose 1 IV

ACTIVE COMPARATOR

Anakinra IV for 21 days

Drug: Anakinra (Kineret®)

Anakinra dose 1 IV/SC

ACTIVE COMPARATOR

Anakinra IV for 14 days \& SC for 7 days

Drug: Anakinra (Kineret®)

Anakinra dose 2 IV

ACTIVE COMPARATOR

Anakinra IV for 21 days

Drug: Anakinra (Kineret®)

Anakinra dose 2 IV/SC

ACTIVE COMPARATOR

Anakinra IV for 14 days \& SC for 7 days

Drug: Anakinra (Kineret®)

Anakinra dose 3 IV

ACTIVE COMPARATOR

Anakinra IV for 21 days

Drug: Anakinra (Kineret®)

Anakinra dose 3 IV/SC

ACTIVE COMPARATOR

Anakinra IV for 14 days \& SC for 7 days

Drug: Anakinra (Kineret®)

Interventions

Anakinra (Kineret®) DRUG

Standard care plus Anakinra for 21 days

Anakinra dose 1 IV; Anakinra dose 1 IV/SC; Anakinra dose 2 IV; Anakinra dose 2 IV/SC; Anakinra dose 3 IV; Anakinra dose 3 IV/SC

Eligibility Criteria

• Age: 24 Weeks - 29 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Monash Medical Centre: lead
• Monash University: collaborator
• Hudson Institute of Medical Research: collaborator
• Liggins Institute: collaborator
• Starship Children's Hospital of New Zealand: collaborator

Study Sites (2)

Monash Children's Hospital

Clayton, Victoria, 3168, Australia

RECRUITING

Starship Children's Hospital

Grafton, Auckland, 1023, New Zealand

NOT YET RECRUITING

MeSH Terms

Conditions

Premature Birth; Inflammation; Bronchopulmonary Dysplasia

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Marcel F Nold, Prof

  Monash Health/ Monash University/ Hudson Institute of Medical Research

  PRINCIPAL INVESTIGATOR

• Claudia Nold, Prof

  Hudson Institute of Medical Research

  PRINCIPAL INVESTIGATOR

• Rod Hunt, Prof

  Monash Health / Monash University

  PRINCIPAL INVESTIGATOR

• Robert Galinsky, Dr

  Hudson Institute of Medical Research

  PRINCIPAL INVESTIGATOR

• Gergely Toldi, Dr

  Starship Children's Hospital / Liggins Institute

  PRINCIPAL INVESTIGATOR

• Carl Kirkpatrick, Prof

  Monash University

  PRINCIPAL INVESTIGATOR

• David Metz, Dr

  Monash Health / Royal Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marcel F Nold, Prof

CONTACT

+61385723936; marcel.nold@monash.edu

Claudia Nold, Prof

CONTACT

+61385723936; claudia.nold@hudson.org.au

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 7, 2025
• First Posted: November 28, 2025
• Study Start: June 27, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 28, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1); AU (1)