Clinical trial NCT03061331: Lumacaftor/Ivacaftor Combination Therapy in Subjects With CF Who Have an A455E CFTR Mutation
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Crossover Study to Evaluate the Efficacy of Lumacaftor/Ivacaftor Combination Therapy in Subjects With Cystic Fibrosis Who Have an A455E-CFTR Mutation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Vertex Pharmaceuticals Incorporated
Sponsor class: INDUSTRY
First posted: 2017-02-23
Enrollment: 20
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, crossover study that will evaluate the efficacy of LUM/IVA in subjects with CF 12 years of age and older who have at least one A455E mutation.


Eligibility criteria: Inclusion Criteria:

* Male or female with confirmed diagnosis of CF
* All subjects must have an A455E mutation on at least 1 CFTR allele; no more than 10 subjects may have an F508del mutation on 1 CFTR allele.
* Forced expiratory volume in one second (FEV1) ≥30% of predicted and ≤90% of predicted at the Screening Visit, based on the Global Lung Function Initiative (GLI)-2012 multi ethnic all-age reference equations.
* Stable CF disease as judged by the investigator.
* Willing to remain on a stable medication regimen for CF from 4 weeks before Day 1 through the Follow up Visit.

Exclusion Criteria:

* History of any comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject.
* A G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R, or R117H mutation on at least one CFTR allele.
* Pregnant or breastfeeding.
* Any abnormal laboratory values at the Screening Visit.
* History of cataract/lens opacity, or evidence of cataract/lens opacity determined to be clinically significant by the ophthalmologist or optometrist during the ophthalmologic examination at the Screening Visit.
* Use of strong inhibitors or strong inducers of CYP3A, including consumption of certain herbal medications and certain fruit and fruit juices, within 14 days before Day 1
* Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements

Primary outcomes:
measure: Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 8
timeFrame: Study Baseline, Through Week 8
Secondary outcomes:
Other outcomes:
Locations:
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis
city: Heidelberglaan
country: Netherlands
facility: University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
Study officials:
References:
citation: Berkers G, van der Meer R, Heijerman H, Beekman JM, Boj SF, Vries RGJ, van Mourik P, Doyle JR, Audhya P, Yuan ZJ, Kinnman N, van der Ent CK. Lumacaftor/ivacaftor in people with cystic fibrosis with an A455E-CFTR mutation. J Cyst Fibros. 2021 Sep;20(5):761-767. doi: 10.1016/j.jcf.2020.11.007. Epub 2020 Nov 26.