Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2 Through 5 Years of Age Homozygous for F508del-CFTR: A Phase 2, Open-Label Clinical Trial.

Stahl, Mirjam; Roehmel, Jobst; Eichinger, Monika; Doellinger, Felix; Naehrlich, Lutz; Kopp, Matthias V; Dittrich, Anna-Maria; Sommerburg, Olaf; Ray, Partha; Maniktala, Anita; Xu, Tu; Conner, Sarah; Joshi, Aniket; Mascia, Molly; Wielpütz, Mark O; Mall, Marcus A (2024). Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2 Through 5 Years of Age Homozygous for F508del-CFTR: A Phase 2, Open-Label Clinical Trial. (In Press). Annals of the American Thoracic Society American Thoracic Society 10.1513/AnnalsATS.202402-201OC

Full text not available from this repository.

RATIONALE

Clinical trials show that lumacaftor/ivacaftor (LUM/IVA) treatment has the potential to modify early cystic fibrosis (CF) disease progression in children as young as 2 years of age.

OBJECTIVE

To assess the long-term impact of LUM/IVA treatment on CF disease progression in children aged 2 through 5 years.

METHODS

This phase 2 trial had two parts: Part 1, a 48-week, randomized, double-blind, placebo-controlled study of LUM/IVA in children aged 2 through 5 years (previously reported) was followed by a 48-week open-label treatment period where all children received LUM/IVA (Part 2; reported here). Endpoints assessed in Part 2 included absolute changes from baseline in chest magnetic resonance imaging (MRI) global score at week 96; weight-for-age, stature-for-age, and body mass index (BMI)-for-age z-scores at week 96; lung clearance index (LCI2.5) through week 96; chest MRI morphological score, chest MRI perfusion score, weight, stature, BMI, and microbiology cultures (oropharyngeal swabs) at week 96; sweat chloride, serum levels of immunoreactive trypsinogen, fecal elastase-1 levels, and fecal calprotectin through week 96; and number of pulmonary exacerbations (PEx), time-to-first PEx, and number of CF-related hospitalizations.

RESULTS

Forty-nine children received ≥1 dose of LUM/IVA in the open-label period (33 in the LUM/IVA to LUM/IVA group and 16 in the placebo to LUM/IVA group); mean exposure 47.1 (SD, 5.2) weeks. The mean absolute change in MRI global score (negative value = improvement) from baseline at Week 96 was -2.7 (SD 7.0; 95% CI, -5.2 to -0.1) in the LUM/IVA to LUM/IVA group and -5.6 (SD 6.9; 95% CI, -9.2 to -1.9) in the placebo to LUM/IVA group. Improvements in LCI2.5, sweat chloride concentration, and markers of pancreatic function and intestinal inflammation were also observed in both groups. Growth parameters remained stable in both groups. The majority of children had adverse events (AEs) considered mild (38.8%) or moderate (40.8%). Two (4.1%) children discontinued LUM/IVA treatment due to AEs (distal intestinal obstruction syndrome [n=1] and alanine aminotransferase increase [n=1]).

CONCLUSION

These findings confirm the potential for early LUM/IVA treatment to alter the trajectory of CF disease progression, including CF lung disease, in children as young as 2 years of age. Clinical trial registration available at www.

CLINICALTRIALS

gov, ID: NCT03625466.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
UniBE Contributor:	Kopp, Matthias Volkmar
Subjects:	600 Technology > 610 Medicine & health
ISSN:	2325-6621
Publisher:	American Thoracic Society
Language:	English
Submitter:	Pubmed Import
Date Deposited:	23 Aug 2024 10:21
Last Modified:	23 Aug 2024 10:21
Publisher DOI:	10.1513/AnnalsATS.202402-201OC
PubMed ID:	39173175
URI:	https://boris.unibe.ch/id/eprint/199935