Clinical trial NCT03795363: Orkambi Treatment in 2 to 5 Year Old Children With CF
Official title: Nutritional Impact of Orkambi Treatment in 2 to 5 Year Old Children Homozygous for F508del Mutations
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cystic Fibrosis
Keywords: CF
CFTR
Cystic Fibrosis
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Vertex Pharmaceuticals Incorporated
First posted: 2019-01-07
Enrollment: 28
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 2 to 5 year old subjects with a diagnosis of cystic fibrosis and homozygous for F508del mutations and who are in a usual state of good health with a clinical decision to start orkambi treatment.

Brief summary: The purpose of this observational research study is to determine the effects of clinically prescribed Orkambi treatment on 2 to 5 year old children homozygous for the F508del Mutations in the Cystic fibrosis transmembrane conductance regulator (CFTR) gene on sleeping energy expenditure, growth status and gut health and function.

Detailed description: Orkambi is a novel FDA approved (August, 2018) therapy for use in patients with cystic fibrosis (CF) who are 2 to 5 years of age and homozygous for F508del mutations in the CFTR gene. It is a combination of lumacaftor and ivacaftor that addresses both the processing and gating defects of the F508del mutation. This investigator-initiated study is designed to evaluate the nutritional, growth and GI impact of Orkambi treatment for this unique younger (2 to 5 years) patient cohort. This proposal extends previous highly informative nutrition and weight gain investigation of ivacaftor treatment in people with CF gating mutations to another CFTR modulator treatment (Orkambi) in people homozygous for F508del mutations. The primary aims of the study are to evaluate the impact of 24 weeks of Orkambi treatment in 2 to 5 year old subjects with CF homozygous for F508del mutations on sleeping or resting energy expenditure, growth status and gut health and function in n=32 children ages 2.0 to 5.9 years of age. Protocol evaluations will occur at baseline (pre-treatment) and 12 and 24 weeks after clinically prescribed Orkambi treatment has begun. Other outcomes of significant clinical interest in young subjects with CF will be explored. All subjects will be evaluated as outpatient at The Children's Hospital of Philadelphia, and will be recruited both regionally and nationally to ensure timely enrollment.

Eligibility criteria: Inclusion Criteria:

* Cystic fibrosis and homozygous for F508del mutations, approved for treatment
* Age: 2.0 to 5.9 years
* In usual state of good health
* A clinical decision has been made for subject to begin Orkambi treatment
* Family committed to the 6 to 8 month study protocol with visits to the Children's Hospital of Philadelphia (CHOP) that will last 2-3 days for the baseline visit (Visit 1) prior to Orkambi and the 24 week visit (Visit 3) after clinically prescribed Orkambi treatment has begun, and will last up to 2 days for the 12 week visit (Visit 2) after Orkambi treatment has begun.

Exclusion Criteria:

* On parenteral nutrition
* Use of any medications that inhibit or induce cytochrome P450 (CYP) 3A
* Liver function tests elevated above 3x the reference range for age and sex
* Lung disease considered severe based on clinical impression by home CF center.
* Other illness affecting growth or nutritional status
* Other contraindications described for Orkambi therapy

Primary outcomes:
measure: Sleeping or Resting Energy Expenditure
timeFrame: 24 Weeks
measure: Anthropometric Assessment
timeFrame: 24 Weeks
Secondary outcomes:
measure: Fecal Elastase I/Pancreatic Function
timeFrame: 24 Weeks
measure: Fecal Calprotectin/Gut Inflammation
timeFrame: 24 Weeks
measure: Plasma Total Fatty Acids
timeFrame: 24 Weeks
Other outcomes:
measure: Dietary Intake
timeFrame: 24 Weeks
measure: Serum fat soluble vitamin levels
timeFrame: 24 Weeks
measure: Changes in bile acid concentration levels
timeFrame: 24 Weeks
measure: Changes in concentration levels of serum calprotectin
timeFrame: 24 Weeks
measure: Muscle-Fat Stores
timeFrame: 24 Weeks
measure: Growth status changes
timeFrame: 24 Weeks
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Virginia Stallings, MD
role: PRINCIPAL_INVESTIGATOR
References:
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