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Orkambi Treatment in 2 to 5 Year Old Children With CF

NCT ID: NCT03795363

Last Updated: 2021-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

28 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-04-10

Study Completion Date

2021-06-16

Brief Summary

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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

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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.

Conditions

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Cystic Fibrosis

Keywords

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CF CFTR Cystic Fibrosis

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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Orkambi

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).

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

2 Years

Maximum Eligible Age

5 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vertex Pharmaceuticals Incorporated

INDUSTRY

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Virginia Stallings, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 30029855 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22383668 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19846789 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27805836 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26510034 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 3937340 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 4044297 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 15343184 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17255835 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27473897 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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18-015669

Identifier Type: -

Identifier Source: org_study_id