Orkambi Treatment in 2 to 5 Year Old Children With CF

Children's Hospital of Philadelphia28 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Cystic Fibrosis

Interventions

OrkambiDRUG

Orkambi is a novel approved therapy for use in people homozygous for the F508del mutation in the CFTR gene. It is a combination of lumacaftor (VX-809) and ivacaftor( VX-770) that addresses both the processing and gating defects of the F508del mutation. The small-molecule corrector lumacaftor corrects the F508del processing defect and increases epithelial delivery of CFTR protein1. Ivacaftor is a CFTR potentiator that increases the channel open probability in F508del-mutant CFTRs that undergo epithelial delivery in vitro and has an additive effect with lumacaftor on chloride transport (2,3,4,5).

Eligibility

Sex: ALLMin age: 2 YearsMax age: 5 Years

Medical Language ↔ Plain English

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

Locations (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Outcomes

Primary Outcomes

Sleeping or Resting Energy Expenditure

Investigators will examine the effects of 24 weeks of orkambi treatment on subject's SEE (sleeping energy expenditure) or REE (resting energy expenditure). Using indirect calorimetry, SEE/REE will be assessed using a computerized metabolic cart Vmax ENCORE at each protocol visit while the child is asleep or resting quietly. SEE/REE will be assessed in the morning if possible and careful note of previous feeding of the child, including the time of day, amount of food, and feeding interval prior to test. It will depend on the age of the subject, and if the subject still takes daily naps and is able to rest quietly without moving, if they will perform sleeping energy expenditure or resting energy expenditure. This will be one outcome measure for each subject, and it will depend on if the subject can nap (SEE) or rest quietly without moving (REE).

Time frame: 24 Weeks

Anthropometric Assessment

Investigators will examine the effects of 24 weeks of orkambi treatment on subject's body mass index (BMI). Investigators will compare the results to BMI Z scores over 24 weeks compared to baseline.

Time frame: 24 Weeks

Secondary Outcomes

Fecal Elastase I/Pancreatic Function

Investigators will examine the effects of 24 weeks of orkambi treatment on subject's pancreatic function. Pancreatic function will be assessed at two visits by obtaining spot stool samples with fecal elastase 1. The concentration of fecal elastase I is indicative of pancreatic function.

Time frame: 24 Weeks

Fecal Calprotectin/Gut Inflammation

Investigators will examine the effects of 24 weeks of orkambi treatment on subject's fecal calprotectin concentration. Spot stool samples will be obtained to determine fecal calprotectin concentration, which is a marker for gut inflammation.

Time frame: 24 Weeks

Plasma Total Fatty Acids

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.