A Study of LJPC-501 in Pediatric Patients With Hypotension

An Open-Label, Multi-Center Study of LJPC-501 in Pediatric Patients Who Remain Hypotensive Despite Receiving Fluid Therapy and Vasopressor Therapy

The objective of this study is to evaluate the effect of LJPC-501 infusion on mean arterial pressure (MAP) or reduction in sum norepinephrine (NE) equivalent dosing, at Hour 2 after the start of LJPC-501, in pediatric patients who remain hypotensive despite receiving fluid therapy and vasopressor therapy. In addition, this study will evaluate the safety and tolerability of LJPC-501 in pediatric patients, the change in MAP over 24 hours after the start of LJPC-501, the change in serum lactate concentrations, and the change in Pediatric Logistic Organ Dysfunction (PELOD) scores.

Study Overview

• Status: Completed
• Conditions: Sepsis; Catecholamine-resistant Hypotension (CRH); Distributive Shock; High Output Shock
• Intervention / Treatment: Drug: Angiotensin II

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78207
      • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 months to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Pediatric patients 2-17 years of age.
2. Patients requiring a total sum NE equivalent dose of > 0.1 μg/kg/min for a minimum of 2 hours and a maximum of 48 hours prior to initiation of LJPC-501 dosing.
3. Patients must have clinical diagnosis of distributive shock in the opinion of the treating team and the Investigator.
4. Patients are required to have central venous access, which is expected to remain present for the duration of LJPC-501 treatment.
5. Patients are required to have an indwelling arterial line, which is expected to remain present for at least the first 24 hours of LJPC-501 treatment.
6. Patients must have received at least 40 mL/kg of crystalloid or colloid equivalent over the initial 24-hour resuscitation period, and are adequately volume resuscitated in the opinion of the Investigator.
7. Parent or legal guardian is willing and able to provide informed consent and assist the patient in complying with all protocol requirements.

Exclusion Criteria:

1. Patients who are < 2 years of age or ≥ 18 years of age.
2. Patients with a standing Do Not Resuscitate order.
3. Patients diagnosed with acute occlusive coronary syndrome requiring pending intervention.
4. Patients on veno-arterial (VA) extracorporeal membrane oxygenation (ECMO).
5. Patients who have been on veno-venous (VV) ECMO for less than 6 hours.
6. Patients with a clinical suspicion of cardiogenic shock.
7. Patients who have a history of asthma or are currently experiencing bronchospasm requiring the use of inhaled bronchodilators and who are not mechanically ventilated.
8. Patients with acute mesenteric ischemia or a history of mesenteric ischemia.
9. Patients with active bleeding AND an anticipated need of multiple transfusions (within 48 hours of Screening).
10. Patients with active bleeding AND hemoglobin < 7 g/dL or any other condition that would contraindicate serial blood sampling.
11. Patients with an absolute neutrophil count (ANC) of < 500 cells/mm3.
12. Patients requiring more than 5 mg/kg daily of hydrocortisone or equivalent glucocorticoid medication as a standing dose.
13. Patients with an expected lifespan of < 12 hours or withdrawal of life support within 24 hours of Screening.
14. Patients with a known allergy to mannitol.
15. Patients who are currently participating in another investigational clinical trial.
16. Patients of childbearing potential who are known to be pregnant at the time of Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LJPC-501; Angiotensin II administered via continuous infusion (1.25 - 40 ng/kg/min) for 24 hours up to 168 hours.	Drug: Angiotensin II; Angiotensin II is a peptide hormone naturally produced by the body that regulates blood pressure via vasoconstriction and sodium reabsorption. LJPC-501 (angiotensin II) is being developed for the treatment of hypotension in patients who do not respond to fluids and vasopressor therapy.; Other Names: Giapreza

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of LJPC-501 on mean arterial pressure (MAP)	To evaluate the effect of LJPC-501 infusion on mean arterial pressure (MAP).	2 hours
Effect of LJPC-501 on sum norepinephrine (NE) equivalent dose	To evaluate the effect of LJPC-501 in the reduction of the sum norepinephrine (NE) equivalent dosing.	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of LJPC-501 on the incidence of treatment-emergent adverse events		Day 7
Effect of LJPC-501 on mean arterial pressure (MAP)	To evaluate the change in MAP over 24 hours after the start of LJPC-501.	24 hours
Effect of LJPC-501 on serum lactate	To evaluate the change in serum lactate concentrations.	2 hours and 24 hours
Effect of LJPC-501 on Pediatric Logistic Organ Dysfunction (PELOD)	To evaluate change in Pediatric Logistic Organ Dysfunction (PELOD) score from Screening to 24 hours. The PELOD score is the sum of 6 individual item scores that totals 0-71 points. A higher PELOD score represents a worse outcome.	24 hours
Effect of LJPC-501 on clinical chemistry laboratory parameters	Safety data for clinical chemistry parameters including ALT, AST, ALP, total bilirubin, direct bilirubin, creatinine, BUN, phosphorus, glucose, albumin, calcium, bicarbonate, chloride, sodium, potassium, magnesium, PT, PTT, and INR. In addition, serum pregnancy test will be assessed at screening to confirm eligibility.	24 hours
Effect of LJPC-501 on hematology laboratory parameters	Safety data for laboratory hematology parameters including hemoglobin, hematocrit, platelets, and WBC.	24 hours
Effect of LJPC-501 on blood pressure	Change in blood pressure (mmHg).	Day 7
Effect of LJPC-501 on heart rate	Change in heart rate (bpm).	Day 7
Effect of LJPC-501 on body temperature	Change in body temperature (Celsius).	Hour 24
Effect of LJPC-501 on general health	Change in physical examination (by body system).	Day 7
Effect of LJPC-501 on electrical activity of the heart	Change in the electrical activity of the heart over a period of time using electrodes placed on the skin and recorded by electrocardiogram (ECG).	Hour 24
Effect of LJPC-501 on urine output	Change in urine output (ml).	Day 7

Collaborators and Investigators

• Sponsor: La Jolla Pharmaceutical Company

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2018
• Primary Completion (Actual): April 14, 2018
• Study Completion (Actual): April 14, 2018

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: February 6, 2018
• First Posted (Actual): February 13, 2018

Study Record Updates

• Last Update Posted (Actual): August 7, 2018
• Last Update Submitted That Met QC Criteria: August 6, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Shock; Hypotension; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Vasoconstrictor Agents; Angiotensin II; Giapreza; Angiotensinogen
• Other Study ID Numbers: LJ501-CRH02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No