Premature InfantsPhase 2AP2NCT07254000
Anakinra Pilot 2 - A Study to Optimise Dose and Route of Administration of Anakinra in Preterm Infants
A Phase 2 study testing Anakinra (Kineret®) in people with Premature Infants and Very Premature Infants, run by Monash Medical Centre at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 24 to 29 weeks
- Conditions the study is for
- Premature Infants, Very Premature Infants, Inflammation
- What is being tested?
- Anakinra (Kineret®)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 27 Jun 2025to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 24 to 29 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Born between 24+0 and 28+6 weeks of gestation
Who cannot join
- Inability of the legal representatives to consent,
- Genetic syndromes,
- Severe cardiac anomalies,
- Substantial pre-/perinatal compromise,
- Congenital diaphragmatic hernia,
- Intrauterine stroke,
Show all 9Show fewer
- Conditions that could confound trial results
- Imminent death or plan for comfort / palliative care
- Infants born outside the recruiting institutions
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
Australia1 site, 1 recruiting
- Recruiting
Monash Children's Hospital
Clayton, Victoria, 3168
Rebecka Atkinson, RN, +61385722713, rebecka.atkinson@hudson.org.au
Marcel F Nold, Prof
New Zealand1 site, 1 recruiting
- Not yet recruiting
Starship Children's Hospital
Grafton, Auckland, 1023
Gergely Toldi, Dr, +64 93670000, gergely.toldi@auckland.ac.nz
Gergely Toldi, Dr
About this study
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.
Read the detailed description
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:
- Establish pharmacokinetics, linearity and target concentration attainment over a range of doses, to determine optimal dosing regimen.
- Assess feasibility and pharmacokinetics of an alternative route of administration (RoA), namely subcutaneous, in week 3 of treatment.
- 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
- Premature Infants, Very Premature Infants, Inflammation
- Being tested
- Anakinra (Kineret®)
- Keywords
- anakinra, bronchopulmonary dysplasia, diffuse white matter injury, very premature infants
- Medical subject headings
- Premature Birth, Inflammation, Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anakinra (Kineret®)Drug
Standard care plus Anakinra for 21 days
| Study group | Role | What they receive |
|---|---|---|
| Anakinra dose 1 IV | Active comparator | Anakinra IV for 21 days Receives: Drug: Anakinra (Kineret®) |
| Anakinra dose 1 IV/SC | Active comparator | Anakinra IV for 14 days \& SC for 7 days Receives: Drug: Anakinra (Kineret®) |
| Anakinra dose 2 IV | Active comparator | Anakinra IV for 21 days Receives: Drug: Anakinra (Kineret®) |
| Anakinra dose 2 IV/SC | Active comparator | Anakinra IV for 14 days \& SC for 7 days Receives: Drug: Anakinra (Kineret®) |
| Anakinra dose 3 IV | Active comparator | Anakinra IV for 21 days Receives: Drug: Anakinra (Kineret®) |
| Anakinra dose 3 IV/SC | Active comparator | Anakinra IV for 14 days \& SC for 7 days Receives: Drug: Anakinra (Kineret®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Day 14-21
Secondary outcomes (10)
Incidence of bronchopulmonary dysplasia
Early efficacy endpoints (exploratory): incidence of bronchopulmonary dysplasia, in comparison to contemporary unit and national statistics.
Measured: 4 months.
Hammersmith infant neurological examination
Early efficacy endpoint (exploratory): Hammersmith infant neurological examination; performed at 3-4 months of corrected age, in comparison to contemporary unit and national statistics.
Measured: 6 months
Incidence of intracranial/intraventricular haemorrhage and peri-ventricular leukomalacia.
Early efficacy endpoint (exploratory): incidence of intracranial/intraventricular haemorrhage and peri-ventricular leukomalacia, in comparison to contemporary unit and national statistics.
Measured: 4 months
Safety of anakinra in extremely premature neonates.
Safety of anakinra IV and SC in premature neonates, at 3 dosing levels, measured as incidence of safety endpoints in particular late-onset sepsis and necrotizing enterocolitis (compared with contemporary unit and national statistics) as well as neutropenia, thrombocytopenia, acute kidney injury, drug-induced liver injury (per Hy's Law).
Measured: 4 weeks
Individual Total Clearance (CL) of anakinra in extremely premature neonates.
Average of individual model-derived estimates of CL will be reported.
Measured: From Baseline up to Day 21.
Individual Volume of Distribution (VD) of anakinra in extremely premature neonates.
Average of individual model-derived estimates of VD will be reported.
Measured: Baseline to Day 21.
Individual Absorption Rate Constant (Ka) of subcutaneously administered anakinra in extremely premature neonates.
Average of individual model-derived estimates of Ka will be reported.
Measured: Day 14-21.
Individual Maximum Serum Concentration (Cmax) of anakinra.
Average of individual model-derived estimates of Cmax will be reported.
Measured: Baseline to Day 21.
Individual Area Under the Concentration-time Curve Within a Dosing Interval (AUCtau) of anakinra.
Average of individual model-derived estimates of AUCtau will be reported.
Measured: Baseline to D21.
Individual Model - derived Ctrough Concentrations of anakinra.
Average of individual model-derived Ctrough concentrations of anakinra will be reported.
Measured: Baseline to D21.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2025
- Study start27 Jun 2025
- Primary completionJun 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Premature InfantsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Monash Medical Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Monash University, Hudson Institute of Medical Research, Liggins Institute, Starship Children's Hospital of New Zealand
- Responsible party
- Sponsor
- Investigators
- Marcel F Nold, Prof, Principal investigator, Monash Health/ Monash University/ Hudson Institute of Medical ResearchClaudia Nold, Prof, Principal investigator, Hudson Institute of Medical ResearchRod Hunt, Prof, Principal investigator, Monash Health / Monash UniversityRobert Galinsky, Dr, Principal investigator, Hudson Institute of Medical ResearchGergely Toldi, Dr, Principal investigator, Starship Children's Hospital / Liggins InstituteCarl Kirkpatrick, Prof, Principal investigator, Monash UniversityDavid Metz, Dr, Principal investigator, Monash Health / Royal Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07254000
- Sponsor's protocol ID
- RES 24-0000-885A
- Acronym
- AP2
- Status last verified
- Sep 2025
- First submitted
- 7 Apr 2025
- Last updated
- 28 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anakinra Pilot 2 - A Study to Optimise Dose and Route of Administration of Anakinra in Preterm Infants
- ClinicalTrials.gov ID
- NCT07254000
- Acronym / sponsor ID
- AP2 / RES 24-0000-885A
- Conditions
- Premature Infants, Very Premature Infants, Inflammation
- Keywords
- anakinra, bronchopulmonary dysplasia, diffuse white matter injury, very premature infants
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Monash Medical CentreUniversity, hospital or other
- Collaborators
- Monash University, Hudson Institute of Medical Research, Liggins Institute, Starship Children's Hospital of New Zealand
- Study start
- 27 Jun 2025 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 28 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- Establish pharmacokinetics, linearity and target concentration attainment over a range of doses, to determine optimal dosing regimen.
- Assess feasibility and pharmacokinetics of an alternative route of administration (RoA), namely subcutaneous, in week 3 of treatment.
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Anakinra dose 1 IV | Active comparator | Drug: Anakinra (Kineret®)Anakinra IV for 21 days |
| Anakinra dose 1 IV/SC | Active comparator | Drug: Anakinra (Kineret®)Anakinra IV for 14 days \& SC for 7 days |
| Anakinra dose 2 IV | Active comparator | Drug: Anakinra (Kineret®)Anakinra IV for 21 days |
| Anakinra dose 2 IV/SC | Active comparator | Drug: Anakinra (Kineret®)Anakinra IV for 14 days \& SC for 7 days |
| Anakinra dose 3 IV | Active comparator | Drug: Anakinra (Kineret®)Anakinra IV for 21 days |
| Anakinra dose 3 IV/SC | Active comparator | Drug: Anakinra (Kineret®)Anakinra IV for 14 days \& SC for 7 days |
Who may qualify
- Ages
- 24 to 29 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Born between 24+0 and 28+6 weeks of gestation
Key exclusion criteria (9 listed)
- Inability of the legal representatives to consent,
- Genetic syndromes,
- Severe cardiac anomalies,
- Substantial pre-/perinatal compromise,
- Congenital diaphragmatic hernia,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anakinra (Kineret®)Standard care plus Anakinra for 21 days | Drug | 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 |
Primary outcome
Population Pharmacokinetics (PopPK) Model of the Clearance of anakinra in extremely premature neonates from birth, during the 3-week treatment period.
Time frame: From Baseline up to Day 21
Point Estimate of Population Total Clearance (CL) of anakinra will be reported.
Population Pharmacokinetics (PopPK) Model of the Volume of Distribution of anakinra in extremely premature neonates from birth, during the 3-week treatment period.
Time frame: From Baseline up to Day 21
Point Estimate of Population Volume of Distribution (VD) of anakinra will be reported.
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.
Time frame: Day 14-21
Point Estimate of Population Absorption of subcutaneously administered anakinra will be reported.
10 secondary outcomes
Incidence of bronchopulmonary dysplasia
Time frame: 4 months.
Hammersmith infant neurological examination
Time frame: 6 months
Incidence of intracranial/intraventricular haemorrhage and peri-ventricular leukomalacia.
Time frame: 4 months
Safety of anakinra in extremely premature neonates.
Time frame: 4 weeks
Individual Total Clearance (CL) of anakinra in extremely premature neonates.
Time frame: From Baseline up to Day 21.
Individual Volume of Distribution (VD) of anakinra in extremely premature neonates.
Time frame: Baseline to Day 21.
Individual Absorption Rate Constant (Ka) of subcutaneously administered anakinra in extremely premature neonates.
Time frame: Day 14-21.
Individual Maximum Serum Concentration (Cmax) of anakinra.
Time frame: Baseline to Day 21.
Individual Area Under the Concentration-time Curve Within a Dosing Interval (AUCtau) of anakinra.
Time frame: Baseline to D21.
Individual Model - derived Ctrough Concentrations of anakinra.
Time frame: Baseline to D21.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Marcel F Nold, Prof principal investigator
Monash Health/ Monash University/ Hudson Institute of Medical Research
Claudia Nold, Prof principal investigator
Hudson Institute of Medical Research
Rod Hunt, Prof principal investigator
Monash Health / Monash University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anakinra (Kineret®) in people with Premature Infants and Very Premature Infants, run by Monash Medical Centre at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marcel F Nold, Prof (+61385723936, marcel.nold@monash.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Population Pharmacokinetics (PopPK) Model of the Clearance of anakinra in extremely premature neonates from birth, during the 3-week treatment period. (time frame: From Baseline up to Day 21). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2025.