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A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele
Abstract
Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in patients ≥12 years of age with cystic fibrosis and at least one F508del-CFTR (cystic fibrosis transmembrane conductance regulator) allele, but it has not been evaluated in children <12 years of age. Objectives: To assess the safety, pharmacokinetics, and efficacy of ELX/TEZ/IVA in children 6 through 11 years of age with F508del–minimal function or F508del-F508del genotypes. Methods: In this 24-week open-label phase 3 study, children (N = 66) weighing <30 kg received 50% of the ELX/TEZ/IVA adult daily dose (ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 h) whereas children weighing ⩾30 kg received the full adult daily dose (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 h). Measurements and Main Results: The primary endpoint was safety and tolerability. The safety and pharmacokinetic profiles of ELX/TEZ/IVA were generally consistent with those observed in older patients. The most commonly reported adverse events included cough, headache, and pyrexia; in most of the children who had adverse events, these were mild or moderate in severity. Through Week 24, ELX/TEZ/IVA treatment improved the percentage of predicted FEV1 (10.2 percentage points; 95% confidence interval [CI], 7.9 to 12.6), Cystic Fibrosis Questionnaire–Revised respiratory domain score (7.0 points; 95% CI, 4.7 to 9.2), lung clearance index2.5 (−1.71 units; 95% CI, −2.11 to −1.30), and sweat chloride (−60.9 mmol/L; 95% CI, −63.7 to −58.2); body mass index-for-age z-score increased over the 24-week treatment period when compared with the pretreatment baseline. Conclusions: Our results show ELX/TEZ/IVA is safe and efficacious in children 6 through 11 years of age with at least one F508del-CFTR allele, supporting its use in this patient population. Clinical trial registered with www.clinicaltrials.gov (NCT03691779).
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“However, clinical studies of ELX/TEZ/IVA completed before the start of the pandemic reported similar robust decreases in the frequency of PEx [ 8-10 , 12 ].”
From Real-world safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: Interim results of a long-term registry-based study (2023) · cites this paper as [10]
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“Phase 3 clinical trials showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in people with cystic fibrosis (CF) with ≥1 F508del-CFTR allele.”
From Real-world safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: Interim results of a long-term registry-based study (2023) · cites this paper as [10]
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Cites
Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele
Middleton, P. G., Mall, M. A., Dřevínek, P., Lands, L. C., McKone, E. F., Polineni, D., Ramsey, B. W., Taylor-Cousar, J. L., Tullis, E., Vermeulen, F., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1908639 · Cited by 2,198
Self-citationA CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation
Ramsey, B. W., Davies, J., McElvaney, N. G., Tullis, E., Bell, S. C., Dřevínek, P., Griese, M., McKone, E. F., Wainwright, C. E., Konstan, M. W., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1105185 · Cited by 2,195
Self-citationHeijerman, H. G. M., McKone, E. F., Downey, D. G., Van Braeckel, E., Rowe, S. M., Tullis, E., Mall, M. A., Welter, J. J., Ramsey, B. W., McKee, C. M., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)32597-8 · Cited by 1,414
Self-citationGrowth and nutritional indexes in early life predict pulmonary function in cystic fibrosis
Konstan, M. W., Butler, S. M., Wohl, M. E. B., Stoddard, M., Matousek, R., Wagener, J. S., Johnson, C. A., & Morgan, W. J. (2003) · The Journal of Pediatrics · doi:10.1067/mpd.2003.152 · Cited by 393
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Cited by
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CFTR modulator therapy: Transforming the landscape of clinical care in cystic fibrosis
Taylor-Cousar, J. L., Robinson, P. D., Shteinberg, M., & Downey, D. G. (2023) · The Lancet · doi:10.1016/s0140-6736(23)01609-4 · Cited by 173
Self-citationBower, J. K., Volkova, N., Ahluwalia, N., Sahota, G., Xuan, F., Chin, A., Weinstock, T. G., Ostrenga, J., & Elbert, A. (2023) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2023.03.002 · Cited by 140
Self-citationPutman, M. S., Norris, A. W., Hull, R. L., Rickels, M. R., Sussel, L., Blackman, S. M., Chan, C. L., Ode, K. L., Daley, T., Stecenko, A. A., et al. (2023) · Diabetes Care · doi:10.2337/dc23-0380 · Cited by 35
Metadata
- Authors
- Zemanick, E. T., Taylor-Cousar, J. L., Davies, J., Gibson, R. L., Mall, M. A., McKone, E. F., McNally, P., Ramsey, B. W., Rayment, J. H., Rowe, S. M., Tullis, E., Ahluwalia, N., Chu, C., Ho, T., Moskowitz, S. M., Noel, S., Tian, S., Waltz, D., Weinstock, T. G., Xuan, F., Wainwright, C. E., & McColley, S. A.
- Affiliations
- Department of Pediatrics, University of Colorado Anschutz Medical Campus and Children’s Hospital Colorado, Aurora, Colorado
- Department of Medicine and
- National Heart and Lung Institute, Imperial College London, National Institute for Health Research Imperial Biomedical Research Centre and Royal Brompton and Harefield National Health Service Foundation Trust, London, United Kingdom
- University of Washington/Seattle Children’s Hospital, Seattle, Washington
- Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité–Universitätsmedizin Berlin, Berlin, Germany
- St. Vincent’s University Hospital and University College, Dublin, Ireland
- Children’s Health Ireland and Royal College of Surgeons in Ireland University of Medicine and Health Sciences, Dublin, Ireland
- British Columbia Children’s Hospital, Vancouver, British Columbia, Canada
- University of Alabama at Birmingham, Birmingham, Alabama
- St. Michael’s Hospital, Toronto, Ontario, Canada
- Vertex Pharmaceuticals Incorporated, Boston, Massachusetts
- University of Queensland, Brisbane, Queensland, Australia
- Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois; and
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-06
- Volume
- 203
- Issue
- 12
- Pages
- 1522-1532
- ISSN
- 1073-449X
- 1535-4970
- PMC
- PMC8483230
- Cited by
- 305
- References
- 4
- Language
- en
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