Anakinra for Preterm Infants Pilot

Study Overview
=================
Brief Summary
-----------------
Phase I/II study of anakinra to prevent the impact of perinatal inflammation in extremely premature infants.

Detailed Description
-----------------
With improvements in antenatal and neonatal care over the last 20 years, now infants are born as early as 22 weeks gestation and survive to discharge from hospital. This increased survival comes with increased risk of long term issues such as cerebral palsy and chronic lung disease. There is strong evidence to show these risks are increased due to an underlying inflammatory process initiated around the time of premature birth. This study aims to prove the safety of treating infants born between 24-27+6 weeks gestation with Anakinra, a medication which is similar to an anti-inflammatory molecule the body makes itself called Interleukin 1 Receptor Antagonist (IL-1Ra). Anakinra acts to reduce the inflammatory response and is currently used in adults and children as young as 8 months to manage autoimmune inflammatory conditions. This study looks at the safety of giving Anakinra to babies born extremely premature, over the first 3 weeks of life. Once safety is established, the investigators will conduct a larger trial studying the efficacy of this treatment for reducing the risk of long-term complications caused by neonatal inflammation in extremely preterm infants.

Official Title
-----------------
Advancing IL-1Ra to Prevent Inflammatory Disease in Preterm Infants - Pilot

Conditions
-----------------
Prematurity; Extreme, Inflammation

Intervention / Treatment
-----------------
* Drug: Anakinra


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Born at 24 to 27+6 weeks gestation Exclusion Criteria: Inability of the legal representatives to consent Any disease or condition that the investigators judge could confound the trial results; these include, but are not limited to, genetic syndromes, severe cardiac abnormalities, substantial pre-/perinatal compromise (profound/severe hypoxia (SaO2 <80% for >3h), congenital diaphragmatic hernia, intrauterine stroke and others. Imminent death

Ages Eligible for Study
-----------------
Minimum Age: 24 Weeks
Maximum Age: 28 Weeks

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Dose escalation
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anakinra<br>First 6 enrolled infants given 1.0mg/kg anakinra alternate daily IV for first 3 weeks of life. Remaining 18 enrolled infants given 0.8mg/kg anakinra daily IV for the first 3 weeks of life, if infant is ≥ 26 weeks gestation. If infant is < 26 weeks gestation, dosing of 1.0mg/kg anakinra alternate daily IV for the first 3 weeks of life, will continue (3 infants only). | Drug: Anakinra<br>* Anakinra will be given to enrolled infants starting in the first 24hrs of life for the first 3 weeks of life.<br>* Other names: Kineret;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related serious adverse reactions (suspected and unexpected) | Monitoring of vital signs and documentation of any significant adverse effects, for the duration of treatment which is 3 weeks, such as cardiorespiratory deterioration requiring escalation of therapy (need to start or increase inotropic medication), need for cardiopulmonary resuscitation, incidence of sepsis and death within 15mins of infusion. Continuously collected physiological data will be summarised as area under the curve in 24h epochs. Serum creatinine will be monitored for incidence of acute kidney injury on days 3, 7 and 14. Liver function will be monitored for incidence of drug-induced liver injury on days 3, 7 and 14. | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma interleukin-1 receptor antagonist levels will be measured and reported in pg/mL for each participant conferred by treatment with anakinra | Blood will be taken prior to commencement of the trial medication, then at 6 & 12hr post-dose on days 1 and 22 and 12hr post dose on day 3, 7 and 14 and the IL-1Ra level recorded in pg/mL. | 22 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
anakinra, IL-1Ra, bronchopulmonary dysplasia, diffuse white matter injury