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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier:
NCT01413581
First received: June 8, 2011
Last updated: July 7, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Prevention of Growth Restriction
Drug: rhBSSL (recombinant human bile-salt-stimulated lipase)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Swedish Orphan Biovitrum:

Primary Outcome Measures:
  • Growth velocity in grams per kilogram per day during 4 weeks of treatment. [ Time Frame: Baseline and Day 29 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in body weight (g) at 3 months [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
  • Body weight (g) at 12 months' corrected age [ Time Frame: 12 months´ corrected age ] [ Designated as safety issue: No ]
  • Body weight (g) at 24 months' corrected age [ Time Frame: 24 months´ corrected age ] [ Designated as safety issue: No ]
  • Change from baseline in total body length (mm) at 4 weeks [ Time Frame: Baseline and Day 29 ] [ Designated as safety issue: No ]
  • Change from baseline in total body length (mm) at 3 months [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
  • Total body length (mm) at 12 months' corrected age [ Time Frame: 12 months' corrected age ] [ Designated as safety issue: No ]
  • Total body height (cm) at 24 months' corrected age [ Time Frame: 24 months' corrected age ] [ Designated as safety issue: No ]
  • Growth restriction [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
    Defined as growth velocity <15 gram per kilogram bodyweight per day during 4 weeks of treatment

  • Time to readiness for discharge [ Time Frame: Baseline and date of readiness for discharge ] [ Designated as safety issue: No ]

    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

  • Time to discharge [ Time Frame: Baseline and date of discharge ] [ Designated as safety issue: No ]
  • Change from baseline in head circumference (mm) at 4 weeks. [ Time Frame: Baseline and Day 29 ] [ Designated as safety issue: No ]
  • Change from baseline in head circumference (mm) at 3 months. [ Time Frame: Baseline and Month 3 ] [ Designated as safety issue: No ]
  • Head circumference (mm) at 12 months' corrected age. [ Time Frame: 12 months´ corrected age ] [ Designated as safety issue: No ]
  • Head circumference (mm) at 24 months' corrected age. [ Time Frame: 24 months´ corrected age ] [ Designated as safety issue: No ]
  • Time from baseline to 150 mL/kg/day of enteral feeding [ Time Frame: Date of first dose and date 150 mL/kg/day of enteral feeding achieved (or exceeded) ] [ Designated as safety issue: No ]
  • Re-admission to hospital within 1 month of discharge [ Time Frame: Date of discharge and date of re-admission ] [ Designated as safety issue: No ]
  • Bayley Scale of Infant and Toddler Development, third edition: Cognitive domain composite score 12 months' corrected age [ Time Frame: 12 months' corrected age ] [ Designated as safety issue: No ]
  • Bayley Scale of Infant and Toddler Development, third edition: Cognitive domain composite score at 24 months' corrected age [ Time Frame: 24 months' corrected age ] [ Designated as safety issue: No ]
  • Bayley Scale of Infant and Toddler Development, third edition: Language domain composite score at 12 months' corrected age [ Time Frame: 12 months' corrected age ] [ Designated as safety issue: No ]
  • Bayley Scale of Infant and Toddler Development, third edition: Language domain composite score at 24 months' corrected age [ Time Frame: 24 months' corrected age ] [ Designated as safety issue: No ]
  • Bayley Scale of Infant and Toddler Development, third edition: Motor domain composite score at 12 months' corrected age [ Time Frame: 12 months' corrected age ] [ Designated as safety issue: No ]
  • Bayley Scale of Infant and Toddler Development, third edition: Motor domain composite score at 24 months' corrected age [ Time Frame: 24 months' corrected age ] [ Designated as safety issue: No ]
  • Bayley Scale of Infant and Toddler Development, third edition: Social-emotional domain composite score at 24 months' corrected age [ Time Frame: 24 months' corrected age ] [ Designated as safety issue: No ]
  • Bayley Scale of Infant and Toddler Development, third edition: Adaptive behavior domain composite score at 24 months' corrected age [ Time Frame: 24 months' corrected age ] [ Designated as safety issue: No ]
  • Neurodevelopment Disability Composite [ Time Frame: 24 months' corrected age ] [ Designated as safety issue: No ]

    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

  • Child Behavior Checklist total problem score at 24 months' corrected age [ Time Frame: 24 months' corrected age visit ] [ Designated as safety issue: No ]
  • Number of patients with at least one treatment emergent Adverse Event [ Time Frame: Baseline and Day 29 ] [ Designated as safety issue: No ]
    Total and by system organ class and preferred term (coded by MedDRA)

  • Number of patients with at least one treatment emergent Adverse Event [ Time Frame: Day 29 and Month 3 ] [ Designated as safety issue: No ]
    Total and by system organ class and preferred term (coded by MedDRA)

  • Number of patients with at least one treatment emergent Serious Adverse Event [ Time Frame: Baseline and Day 29 ] [ Designated as safety issue: No ]
    Total and by system organ class and preferred term (coded by MedDRA)

  • Number of patients with at least one treatment emergent Serious Adverse Event [ Time Frame: Day 29 and Month 3 ] [ Designated as safety issue: No ]
    Total and by system organ class and preferred term (coded by MedDRA)

  • Number of patients with at least one Serious Adverse Drug Reaction [ Time Frame: 12 months' corrected age and 24 months' corrected age ] [ Designated as safety issue: No ]
    Total and by system organ class and preferred term (coded by MedDRA)

  • Level of Vitamin A (nmol/L) at 4 weeks [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Level of Vitamin D (nmol/L) at 4 weeks [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Number of outpatient visits from the time of initial hospital discharge to home up to 24 months' corrected age [ Time Frame: Date of initial hospital discharge to home to date of 24 months' corrected age ] [ Designated as safety issue: No ]
  • Number of inpatient visits from the time of initial hospital discharge to home up to 24 months' corrected age [ Time Frame: Date of initial hospital discharge to home to date of 24 months' corrected age ] [ Designated as safety issue: No ]
  • Number of days of hospitalization from the time of initial hospital discharge to home up to 24 months' corrected age [ Time Frame: Date of initial hospital discharge to home to date of 24 months' corrected age ] [ Designated as safety issue: No ]
  • Number of days in intensive care unit from the time of initial hospital discharge to home up to 24 months' corrected age [ Time Frame: Date of initial hospital discharge to home to date of 24 months' corrected age ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Date of initial hospital discharge to home to date of 24 months' corrected age ] [ Designated as safety issue: No ]
  • Presence of chronic medical conditions/diagnoses at 24 months' corrected age [ Time Frame: 24 months' corrected age ] [ Designated as safety issue: No ]
  • Docosahexaenoic acid (% of total fatty acids) in the serum triglyceride fraction at 4 weeks [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Docosahexaenoic acid (% of total fatty acids) in the serum phosphatidylcholine fraction at 4 weeks [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Arachidonic acid (% of total fatty acids) in the serum triglyceride fraction at 4 weeks [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Arachidonic acid (% of total fatty acids) in the serum phosphatidylcholine fraction at 4 weeks [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Number of patients with antibodies to rhBSSL at 4 weeks [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  • Number of patients with antibodies to rhBSSL at Month 3 [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
  • Number of patients with antibodies to rhBSSL at 12 months' corrected age [ Time Frame: 12 months' corrected age ] [ Designated as safety issue: No ]

Estimated Enrollment: 432
Study Start Date: May 2011
Estimated Study Completion Date: August 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rhBSSL
rhBSSL (recombinant human bile-salt-stimulated lipase)
Drug: rhBSSL (recombinant human bile-salt-stimulated lipase)
rhBSSL added to infant formula/pasteurized breast milk during a 4 week treatment period.
Placebo Comparator: Placebo
Placebo
Drug: Placebo
Placebo added to infant formula/pasteurized breast milk during a 4 week treatment period.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 10 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01413581

  Hide Study Locations
Locations
Belgium
Swedish Orphan Biovitrum Investigational Site
Bruges, Belgium
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Leuven, Belgium
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Liege, Belgium
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Rocourt, Belgium
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Wilrijk, Belgium
Czech Republic
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Hradec Kralove, Czech Republic
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Olomouc, Czech Republic
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Prague, Czech Republic
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Zlin, Czech Republic
France
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Amiens, France
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Lille, France
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Nancy, France
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Paris, France
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Rouen, France
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Strasbourg, France
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Toulouse, France
Germany
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Berlin, Germany
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Freiburg, Germany
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Heidelberg, Germany
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Wiesbaden, Germany
Hungary
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Budapest, Hungary
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Gyula, Hungary
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Miskolc, Hungary
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Nyíregyháza, Hungary
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Pécs, Hungary
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Veszprem, Hungary
Italy
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Ancona, Italy
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Bari, Italy
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Foggia, Italy
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Milano, Italy
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Padova, Italy
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Roma, Italy
Poland
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Bydgoszcz, Poland
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Gdansk, Poland
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Lodz, Poland
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Poznan, Poland
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Warszawa, Poland
Russian Federation
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Ivanovo, Russian Federation
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Nizhniy Novgorod, Russian Federation
Spain
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Almería, Spain
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Cádiz, Spain
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Córdoba, Spain
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Madrid, Spain
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Málaga, Spain
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Oviedo, Spain
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Salamanca, Spain
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Santiago de Compostela, Spain
Sweden
Swedish Orphan Biovitrum Investigational Site
Stockholm, Sweden
Swedish Orphan Biovitrum Investigational Site
Umeå, Sweden
Sponsors and Collaborators
Swedish Orphan Biovitrum
Investigators
Study Director: Kristina Timdahl, MD Swedish Orphan Biovitrum
  More Information

No publications provided

Responsible Party: Swedish Orphan Biovitrum
ClinicalTrials.gov Identifier: NCT01413581     History of Changes
Other Study ID Numbers: BVT.BSSL-030
Study First Received: June 8, 2011
Last Updated: July 7, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Czech Republic: State Institute for Drug Control
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Swedish Orphan Biovitrum:
rhBSSL
preterm infants
Swedish Orphan Biovitrum
growth velocity
Prevention of growth restriction

Additional relevant MeSH terms:
Bile Acids and Salts
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014