A Study of LJPC-501 in Paediatric Patients With Hypotension Associated With Distributive or Vasodilatory Shock

Study Overview
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Brief Summary
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The objective of this study is to evaluate the effect of LJPC-501 infusion on mean arterial pressure (MAP) as assessed by standard of care vasopressor dose reduction in pediatric patients with catecholamine-resistant hypotension (CRH). In addition, this study will evaluate the safety and tolerability of LJPC-501 in pediatric patients, evaluate changes in catecholamine and other vasopressor doses over time, evaluate the change in MAP over time, and the change in Pediatric Logistic Organ Dysfunction-2 (PELOD-2) scores.

Official Title
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A Randomised, Placebo-controlled, Double-Blind, Multicentre Efficacy and Safety Study of LJPC-501 in Paediatric Patients > 2 to 17 Years of Age With Catecholamine-Resistant Hypotension Associated With Distributive Shock

Conditions
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Catecholamine-resistant Hypotension (CRH), Distributive Shock, High Output Shock, Septic Shock

Intervention / Treatment
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* Drug: LJPC-501 (angiotensin II)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female paediatric patients with catecholamine-resistant hypotension associated with distributive shock. Paediatric patients > 2 years (ie, > 24 months) to < 18 years of age at enrolment. Patients requiring a sum norepinephrine-equivalent dose > 0.1 μg/kg/min to maintain age-appropriate target MAP for a minimum of 2 hours and a maximum of 48 hours prior to initiation of study drug. Patients must have a clinical diagnosis of distributive shock in the opinion of the treating team and the Investigator. Patients are required to have central venous access, which is expected to remain present for the duration of study drug treatment. Patients are required to have an indwelling arterial line, which is expected to remain present for at least the first 48 hours of study drug treatment. Patients must have received at least 40 mL/kg of crystalloid or colloid equivalent over the initial 24-hour resuscitation period, and must be adequately volume resuscitated in the opinion of the Investigator, prior to starting study drug. Parent(s) or legal guardian(s) is willing and able to provide informed consent and assist the patient in complying with all protocol requirements. Exclusion Criteria: Patients who are ≤ 2 years (24 months) of age or ≥ 18 years of age at enrolment. Patients with a standing Do Not Resuscitate order. Patients diagnosed with acute occlusive coronary syndrome requiring pending intervention. Patients on veno-arterial (VA) extracorporeal membrane oxygenation (ECMO). Patients who have been on veno-venous (VV) ECMO for less than 6 hours. Patients with a clinical suspicion of cardiogenic shock based on echocardiogram. Patients who have a history of asthma or are currently experiencing bronchospasm requiring the use of inhaled bronchodilators and who are not mechanically ventilated. Patients with acute mesenteric ischaemia or a history of mesenteric ischaemia. Patients with active bleeding AND an anticipated need of multiple transfusions (within 48 hours of Screening). Patients with active bleeding AND haemoglobin < 7 g/dL. Patients with an expected lifespan of < 12 hours or expected withdrawal of life support within 24 hours of Screening. Patients with a known allergy to mannitol. Patients who are currently participating in another clinical trial using an investigational drug not approved in that member country unless specifically approved by the Sponsor. Patients of childbearing potential who are known to be pregnant at the time of Screening.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Comparator: LJPC-501<br>LJPC-501 Angiotensin II Solution for infusion | Drug: LJPC-501 (angiotensin II)<br>* Angiotensin II is a peptide hormone naturally produced by the body that regulates blood pressure via vasoconstriction and sodium reabsorption.<br>|
| Placebo Comparator: Placebo Comparator: Placebo<br>0.9% sodium chloride solution | Drug: Placebo<br>* Placebo Arm<br>* Other names: 0.9% sodium chloride solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who have a >/= 50% reduction in norepinephrine equivalent doses (NED) |  | Hour 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on Paediatric Logistic Organ Dysfunction-2 (PELOD-2) based on treatment with LJPC-501 | Change in PELOD-2 score from baseline to 24 hours and 48 hours after start of LJPC-501. The PELOD-2 score is the sum of 5 individual item scores that totals 0-31 points. A higher PELOD-2 score represents a worse outcome. | Baseline, Hour 24 and Hour 48 | 
| Effect on total catecholamine doses administered based on treatment with LJPC-501 | Change in total catecholamine doses administered from baseline to 24 hours and 48 hours after start of LJPC-501. | Baseline, Hour 24 and Hour 48 | 
| Effect on mean arterial pressure (MAP) based on treatment with LJPC-501 | Change in MAP from baseline to 3 hours, 24 hours and 48 hours after start of LJPC-501 | Baseline, Hour 3, Hour 24, and Hour 48 | 
| Effect on heart rate based on treatment with LJPC-501 | Change in heart rate from baseline to 3 hours, 24 hours and 48 hours after start of LJPC-501 | Baseline to Hour 3, Hour 24, and Hour 48 | 
| Assessment of safety based on number of patients with treatment emergent adverse events based on treatment with LJPC-501 |  | Day 7 | 
| Assessment of tolerability based on the effect on clinical chemistry parameters based on treatment with LJPC-501 | Safety data for clinical chemistry parameters including ALT, AST, ALP, total bilirubin, direct bilirubin, creatinine, BUN, lactate, phosphorous, glucose, albumin, calcium, bicarbonate, chloride, sodium, potassium, magnesium | Hour 24 and Hour 48 |