Comparison of rhBSSL With Placebo When Added to Infant Formula or Pasteurized Breast Milk During 4 Weeks of Treatment in Preterm Infants

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that rhBSSL improves growth in preterm infants as compared with placebo.

Detailed Description
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The purpose of this study is to demonstrate that rhBSSL improves growth in preterm infants as compared with placebo. The infants should be born before week 32 of gestational age. The study drug, rhBSSL or placebo, will be administered during a 4 week treatment period by adding it to either infant formula or pasteurized breast milk. The study will also evaluate the safety and tolerability of rhBSSL. Eligible patients will be randomized in a ratio of 1:1 (rhBSSL:placebo). The study consists of maximum 1 week screening period, a 4-week treatment period and a 2 year follow-up period.

Official Title
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A Prospective, Randomized, Double-Blind, Phase 3 Study Comparing rhBSSL and Placebo Added to Infant Formula or Pasteurized Breast Milk During 4 Weeks of Treatment in Preterm Infants Born Before Week 32 of Gestational Age

Conditions
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Prevention of Growth Restriction

Intervention / Treatment
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* Drug: rhBSSL (recombinant human bile-salt-stimulated lipase)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Preterm infants born before week 32 of gestation. Preterm infant who is less than 33 weeks postmenstrual age at the time of randomization. Preterm infant who is appropriate for gestational age (AGA) or small for gestational age (SGA) at birth. Preterm infant who is receiving food enterally (bottle or gavage tube) at a level of at least 100 ml/kg/day at randomization. Preterm infant whose enteral feeding consists of only infant formula or only pasteurized breast milk at the time of inclusion, and who are expected to remain on only infant formula for 4 weeks, or only pasteurized breast milk for at least 2 weeks following treatment initiation. Preterm infant who is expected not to receive any fresh breast milk for 4 weeks following treatment initiation. Informed consent is obtained. Exclusion Criteria: Expected stay in the hospital is less than 4 weeks from the first dose of study drug. Criteria to ensure no disease or treatment affecting growth or development, e.g. brain disease, necrotizing enterocolitis. Enrolled in another concurrent clinical intervention study.

Ages Eligible for Study
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Maximum Age: 10 Weeks

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rhBSSL<br>rhBSSL (recombinant human bile-salt-stimulated lipase) | Drug: rhBSSL (recombinant human bile-salt-stimulated lipase)<br>* rhBSSL added to infant formula/pasteurized breast milk during a 4 week treatment period.<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo added to infant formula/pasteurized breast milk during a 4 week treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth velocity in grams per kilogram per day during 4 weeks of treatment. |  | Baseline and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in body weight (g) at 3 months |  | Baseline and Month 3 | 
| Body weight (g) at 12 months' corrected age |  | 12 months´ corrected age | 
| Body weight (g) at 24 months' corrected age |  | 24 months´ corrected age | 
| Change from baseline in total body length (mm) at 4 weeks |  | Baseline and Day 29 | 
| Change from baseline in total body length (mm) at 3 months |  | Baseline and Month 3 | 
| Total body length (mm) at 12 months' corrected age |  | 12 months' corrected age | 
| Total body height (cm) at 24 months' corrected age |  | 24 months' corrected age | 
| Growth restriction | Defined as growth velocity <15 gram per kilogram bodyweight per day during 4 weeks of treatment | Day 29 | 
| Time to readiness for discharge | Time until each of the following are fulfilled sustained weight gain (weight of 1800 g sustained for three days) ability to maintain normal body temperature ability to suckle feed ability to maintain stable cardiorespiratory function | Baseline and date of readiness for discharge | 
| Time to discharge |  | Baseline and date of discharge | 
| Change from baseline in head circumference (mm) at 4 weeks. |  | Baseline and Day 29 | 
| Change from baseline in head circumference (mm) at 3 months. |  | Baseline and Month 3 | 
| Head circumference (mm) at 12 months' corrected age. |  | 12 months´ corrected age | 
| Head circumference (mm) at 24 months' corrected age. |  | 24 months´ corrected age | 
| Time from baseline to 150 mL/kg/day of enteral feeding |  | Date of first dose and date 150 mL/kg/day of enteral feeding achieved (or exceeded) | 
| Re-admission to hospital within 1 month of discharge |  | Date of discharge and date of re-admission | 
| Bayley Scale of Infant and Toddler Development, third edition: Cognitive domain composite score 12 months' corrected age |  | 12 months' corrected age | 
| Bayley Scale of Infant and Toddler Development, third edition: Cognitive domain composite score at 24 months' corrected age |  | 24 months' corrected age | 
| Bayley Scale of Infant and Toddler Development, third edition: Language domain composite score at 12 months' corrected age |  | 12 months' corrected age | 
| Bayley Scale of Infant and Toddler Development, third edition: Language domain composite score at 24 months' corrected age |  | 24 months' corrected age | 
| Bayley Scale of Infant and Toddler Development, third edition: Motor domain composite score at 12 months' corrected age |  | 12 months' corrected age | 
| Bayley Scale of Infant and Toddler Development, third edition: Motor domain composite score at 24 months' corrected age |  | 24 months' corrected age | 
| Bayley Scale of Infant and Toddler Development, third edition: Social-emotional domain composite score at 24 months' corrected age |  | 24 months' corrected age | 
| Bayley Scale of Infant and Toddler Development, third edition: Adaptive behavior domain composite score at 24 months' corrected age |  | 24 months' corrected age | 
| Neurodevelopment Disability Composite | Presence of : Composite score of less than 70 on any of the cognitive, language or motor domains of Bayley scale of infant and toddler development, third edition Bilateral deafness Bilateral blindness Cerebral palsy | 24 months' corrected age | 
| Child Behavior Checklist total problem score at 24 months' corrected age |  | 24 months' corrected age visit | 
| Number of patients with at least one treatment emergent Adverse Event | Total and by system organ class and preferred term (coded by MedDRA) | Baseline and Day 29 | 
| Number of patients with at least one treatment emergent Adverse Event | Total and by system organ class and preferred term (coded by MedDRA) | Day 29 and Month 3 | 
| Number of patients with at least one treatment emergent Serious Adverse Event | Total and by system organ class and preferred term (coded by MedDRA) | Baseline and Day 29 | 
| Number of patients with at least one treatment emergent Serious Adverse Event | Total and by system organ class and preferred term (coded by MedDRA) | Day 29 and Month 3 | 
| Number of patients with at least one Serious Adverse Drug Reaction | Total and by system organ class and preferred term (coded by MedDRA) | 12 months' corrected age and 24 months' corrected age | 
| Level of Vitamin A (nmol/L) at 4 weeks |  | Day 29 | 
| Level of Vitamin D (nmol/L) at 4 weeks |  | Day 29 | 
| Number of outpatient visits from the time of initial hospital discharge to home up to 24 months' corrected age |  | Date of initial hospital discharge to home to date of 24 months' corrected age | 
| Number of inpatient visits from the time of initial hospital discharge to home up to 24 months' corrected age |  | Date of initial hospital discharge to home to date of 24 months' corrected age | 
| Number of days of hospitalization from the time of initial hospital discharge to home up to 24 months' corrected age |  | Date of initial hospital discharge to home to date of 24 months' corrected age | 
| Number of days in intensive care unit from the time of initial hospital discharge to home up to 24 months' corrected age |  | Date of initial hospital discharge to home to date of 24 months' corrected age | 
| Number of days lost from work related to the child's condition from the time of initial hospital discharge to home up to 24 months' corrected age |  | Date of initial hospital discharge to home to date of 24 months' corrected age | 
| Presence of chronic medical conditions/diagnoses at 24 months' corrected age |  | 24 months' corrected age | 
| Docosahexaenoic acid (% of total fatty acids) in the serum triglyceride fraction at 4 weeks |  | Day 29 | 
| Docosahexaenoic acid (% of total fatty acids) in the serum phosphatidylcholine fraction at 4 weeks |  | Day 29 | 
| Arachidonic acid (% of total fatty acids) in the serum triglyceride fraction at 4 weeks |  | Day 29 | 
| Arachidonic acid (% of total fatty acids) in the serum phosphatidylcholine fraction at 4 weeks |  | Day 29 | 
| Number of patients with antibodies to rhBSSL at 4 weeks |  | Day 29 | 
| Number of patients with antibodies to rhBSSL at Month 3 |  | Month 3 | 
| Number of patients with antibodies to rhBSSL at 12 months' corrected age |  | 12 months' corrected age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rhBSSL, preterm infants, Swedish Orphan Biovitrum, growth velocity, Prevention of growth restriction