Orkambi Treatment in 2 to 5 Year Old Children With CF

NCT03795363 | Completed DMC FDA Drug

• 1 other identifier: 18-015669
• Study Type: observational
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystic Fibrosis

Keywords

CF; CFTR; Cystic Fibrosis

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  24 Weeks

Secondary Outcomes (3)

• Fecal Elastase I/Pancreatic Function

  24 Weeks

• Fecal Calprotectin/Gut Inflammation

  24 Weeks

• Plasma Total Fatty Acids

  24 Weeks

Other Outcomes (6)

• Dietary Intake

  24 Weeks

• Serum fat soluble vitamin levels

  24 Weeks

• Changes in bile acid concentration levels

  24 Weeks

Interventions

Orkambi DRUG

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 Criteria

• Age: 2 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• Vertex Pharmaceuticals Incorporated: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19146, United States

Location

Related Publications (13)

• Stallings VA, Sainath N, Oberle M, Bertolaso C, Schall JI. Energy Balance and Mechanisms of Weight Gain with Ivacaftor Treatment of Cystic Fibrosis Gating Mutations. J Pediatr. 2018 Oct;201:229-237.e4. doi: 10.1016/j.jpeds.2018.05.018. Epub 2018 Jul 18.

  PMID: 30029855 BACKGROUND

• Flume PA, Liou TG, Borowitz DS, Li H, Yen K, Ordonez CL, Geller DE; VX 08-770-104 Study Group. Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation. Chest. 2012 Sep;142(3):718-724. doi: 10.1378/chest.11-2672.

  PMID: 22383668 BACKGROUND

• Van Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T, Turnbull A, Singh A, Joubran J, Hazlewood A, Zhou J, McCartney J, Arumugam V, Decker C, Yang J, Young C, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu P. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18825-30. doi: 10.1073/pnas.0904709106. Epub 2009 Oct 21.

  PMID: 19846789 BACKGROUND

• Milla CE, Ratjen F, Marigowda G, Liu F, Waltz D, Rosenfeld M; VX13-809-011 Part B Investigator Group *. Lumacaftor/Ivacaftor in Patients Aged 6-11 Years with Cystic Fibrosis and Homozygous for F508del-CFTR. Am J Respir Crit Care Med. 2017 Apr 1;195(7):912-920. doi: 10.1164/rccm.201608-1754OC.

  PMID: 27805836 BACKGROUND

• Wainwright CE, Elborn JS, Ramsey BW. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Oct 29;373(18):1783-4. doi: 10.1056/NEJMc1510466. No abstract available.

  PMID: 26510034 BACKGROUND

• Energy and protein requirements. Report of a joint FAO/WHO/UNU Expert Consultation. World Health Organ Tech Rep Ser. 1985;724:1-206. No abstract available.

  PMID: 3937340 BACKGROUND

• Schofield WN. Predicting basal metabolic rate, new standards and review of previous work. Hum Nutr Clin Nutr. 1985;39 Suppl 1:5-41.

  PMID: 4044297 BACKGROUND

• World Health Organization. WHO Child Growth Standards: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height, and body mass index-for-age. Geneva, Switzerland: WHO Press, World Health Organization; 2006.

  BACKGROUND

• Borowitz D, Baker SS, Duffy L, Baker RD, Fitzpatrick L, Gyamfi J, Jarembek K. Use of fecal elastase-1 to classify pancreatic status in patients with cystic fibrosis. J Pediatr. 2004 Sep;145(3):322-6. doi: 10.1016/j.jpeds.2004.04.049.

  PMID: 15343184 BACKGROUND

• Borowitz D, Lin R, Baker SS. Comparison of monoclonal and polyclonal ELISAs for fecal elastase in patients with cystic fibrosis and pancreatic insufficiency. J Pediatr Gastroenterol Nutr. 2007 Feb;44(2):219-23. doi: 10.1097/MPG.0b013e31802c41de.

  PMID: 17255835 BACKGROUND

• O'Connor MG, Seegmiller A. The effects of ivacaftor on CF fatty acid metabolism: An analysis from the GOAL study. J Cyst Fibros. 2017 Jan;16(1):132-138. doi: 10.1016/j.jcf.2016.07.006. Epub 2016 Jul 26.

  PMID: 27473897 BACKGROUND

• World Health Organization. WHO Child Growth Standards: Head circumference-for-age, arm circumference-for-age, triceps skinfold-for-age, and subscapular skinfold-for-age. Geneva, Switzerland: WHO Press, World Health Organization; 2007.

  BACKGROUND

• WHO Multicenter Growth Reference Study Group. WHO Child Growth Standards: Growth Velocity Based on Weight, Length and Head Circumference: Methods and Development. Geneva, Switzerland: WHO Press: World Health Organization; 2009.

  BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood, stool sample

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

lumacaftor, ivacaftor drug combination

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Virginia Stallings, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2018
• First Posted: January 7, 2019
• Study Start: April 10, 2019
• Primary Completion: June 16, 2021
• Study Completion: June 16, 2021
• Last Updated: December 2, 2021

Record last verified: 2021-12

Locations

US (1)