Pediatric Study to Evaluate Risk of Developing Essential Fatty Acid Deficiency When Receiving Clinolipid or Standard-of-Care Lipid Emulsion (Part A)

Study Overview
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Brief Summary
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This will be a descriptive study designed to evaluate the propensity for hospitalized pediatric patients treated adequately with Clinolipid or standard of care (Intralipid) from 7 up to 90 days to develop Essential Fatty Acid Deficiency (EFAD). Additionally, this study design will evaluate the safety and efficacy of using Clinolipid or Intralipid in a pediatric population.

Official Title
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A Randomized, Double-Blind, Controlled, Clinical Trial to Evaluate the Risk of Developing Essential Fatty Acid Deficiency in Pediatric Patients, Including Neonates, Receiving Either Clinolipid (Lipid Injectable Emulsion, USP) 20% or Standard-of-Care Soybean Oil-Based Lipid Emulsion (Part A)

Conditions
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Essential Fatty Acid Deficiency (EFAD)

Intervention / Treatment
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* Drug: Clinolipid
* Drug: Intralipid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients and/or their legal representative must be able to understand the study and voluntarily sign the informed consent form (ICF) per 21 CFR Part 50.55(e) Patients and/or their legal representative accept adherence to protocol requirements Patients who are expected to require parenteral nutrition (PN)for at least 7 days Premature infants (born at 24 to <37 weeks of gestation with a birth weight ≥750g) require at least 80% of targeted energy requirements by PN at study entry (up to 1 month CA); full term infants and children require at least 70% of targeted energy requirements by PN at study entry Exclusion Criteria: Patients who are not expected to survive hospitalization or with a severe critical unresponsive illness at time of initiation with foreseeable intercurrent events that could jeopardize the patient's participation in the study, as judged by the Investigator (e.g., unresponsive shock, sepsis, renal failure requiring dialysis, severe unresponsive metabolic acidosis, and/or severe unresponsive metabolic disorders); Patients with a known hypersensitivity to lipid emulsion, egg or soybean proteins, or any of the active substances, excipients, or components of the container or who have a history of an adverse event due to ILE; Patients with liver disease including cholestasis; Patients with severe hyperlipidemia or severe disorders of lipid metabolism characterized by hypertriglyceridemia (triglyceride >400 mg/dL); Patients who are unable to tolerate the necessary laboratory monitoring; Patients who are enrolled in another clinical trial involving an investigational agent; Patients with a known history of either severe hemorrhagic or severe hemolytic disease as judged by the investigator; Premature infants born <24 weeks of gestation and patients ≥18 years; Premature infants with a birth weight <750 g; Patient requires or is expected to require propofol for sedation; Patient has received a diagnosis of Coronavirus Disease of 2019 (COVID-19) (diagnosis <2 months prior and/or symptoms have not resolved. Newborn patient born to a mother who was diagnosed as COVID-19 positive at delivery or within 2 months prior to delivery Female patients who are pregnant. Note: All female patients ≥12 years of age must have a negative urine human chorionic gonadotropin (hCG) pregnancy test at screening. For female patients <12 years of age, a urine hCG test at screening will be performed at the discretion of the investigator based on childbearing potential.

Ages Eligible for Study
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Minimum Age: 0 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clinolipid<br>Dosing based on American Academy of Pediatrics (AAP), American Academy Society for Parenteral and Enteral Nutrition (ASPEN), European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN)/ European Society for Parenteral and Enteral Nutrition (ESPEN)/ European Society of Paediatric Research (ESPR)/ Chinese Society for Parenteral and Enteral Nutrition (CSPEN) guidelines. Study treatment will be administered intravenously in the hospital setting from 7 up to 90 days using either a syringe pump or an infusion pump as appropriate for the daily volume of infusate. The flow rate will be prescribed by the Investigator to provide the daily dosage over 20 to 24 hours. | Drug: Clinolipid<br>* Lipid injectable emulsion, USP 20%<br>|
| Active Comparator: Intralipid<br>Dosing based on AAP, ASPEN, ESPGHAN/ESPEN/ESPR/CSPEN guidelines. Study treatment will be administered intravenously in the hospital setting from 7 up to 90 days using either a syringe pump or an infusion pump as appropriate for the daily volume of infusate. The flow rate will be prescribed by the Investigator to provide the daily dosage over 20 to 24 hours. | Drug: Intralipid<br>* Standard-of-Care Soybean Oil-Based Lipid Emulsion. 20% (lipid injectable emulsion, USP)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants to Develop Essential Fatty Acid Deficiency (EFAD) Defined by Holman Index > 0.4 | Holman Index is the plasma Triene:Tetraene ratio, specifically 5,8,11-eicosatrienoic acid [mead acid] to 5,8,11,14 eicosatetraenoic acid [arachidonic acid, [ARA] ratio | Up to Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants to Develop Parenteral Nutrition-Associated Liver Disease (PNALD) | Defined by direct bilirubin ≥2 mg/dL in patients receiving with intravenous lipid emulsion (ILE). | Up to Day 90 | 
| Alkaline Phosphatase (ALP) | Plasma liver function test | Up to Day 90 | 
| Aspartate Aminotransferase (AST) | Plasma liver function test | Up to Day 90 | 
| Alanine Aminotransferase (ALT) | Plasma liver function test | Up to Day 90 | 
| Gamma-Glutamyl Transferase (GGT) | Plasma liver function test | Up to Day 90 | 
| Total Bilirubin | Plasma liver function test | Up to Day 90 | 
| Direct Bilirubin | Plasma liver function test | Up to Day 90 | 
| Stigmasterol Blood Level | Phytosterol species | Up to Day 90 | 
| Campesterol Blood Level | Phytosterol species | Up to Day 90 | 
| Sitosterol Blood Level | Phytosterol species. | Up to day 90 | 
| Cholesterol Blood Level |  | Up to Day 90 | 
| Squalene Blood Level |  | Up to Day 90 | 
| Calories Nutritional Intake |  | Up to Day 90 | 
| Protein Nutritional Intake |  | Up to Day 90 | 
| Lipid Nutritional Intake |  | Up to Day 90 | 
| Carbohydrates Nutritional Intake |  | Up to Day 90 | 
| Change in Length or Height (and Head Circumference for Infants <1 Year of Age) From Baseline | Change in length/height from baseline (mm/week in all) = [Length (mm) on Day X - Length (mm) at baseline] / [X/7] Change in head circumference from baseline (mm/week in infants <1 year) = [Head circumference (mm) on Day X - Head circumference (mm) at baseline] / [X/7] | Up to Day 90 | 
| Body Weight | Change in Weight. from baseline (g/kg/day) to EOT for infants < 1 year of Age | Up to day 90 | 
| Body Weight | Change in weight from baseline to end of treatment (EOT) for those > 1 year of age (g/day) | Upto Day 90 | 
| Number of Adverse Events of Special Interest |  | Up to Day 120 (30 Days After Subject's Last Study Treatment if hospital discharge has not occurred) | 
| Number of Participants With Neonatal Morbidities | Neonatal Morbidities are presented for premature infants born < 37 weeks of gestation up to 1 month corrected age. Patients may have more than 1 neonatal morbidity. | Up to Day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Essential Fatty Acids (EFA), Parenteral Nutrition, Clinolipid/Clinoleic, Parenteral Nutrition Associated Cholestasis (PNAC), Parenteral Nutrition Associated Liver Disease (PNALD), Intestinal Failure Associated Liver Disease (IFALD), Phytosterols, Intralipid, Infants/Preterm Infants, FADS1 and FADS2, Short Bowel Syndrome, Cancer Nutrition, Olive Oil Emulsion, Soybean Oil Emulsion