Lumacaftor/Ivacaftor Combination Therapy in Subjects With CF Who Have an A455E CFTR Mutation

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: LUM/IVA
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Sequence 1<br>LUM/IVA in Treatment Period 1; washout; placebo in Treatment Period 2 | Drug: LUM/IVA<br>* LUM 400 mg/IVA 250 mg every 12 hours (q12h)<br>* Other names: lumacaftor/ivacaftor;Drug: Placebo<br>* No Active Drug<br>|
| Experimental: Treatment Sequence 2<br>Placebo in Treatment Period 1; washout; LUM/IVA in Treatment Period 2 | Drug: LUM/IVA<br>* LUM 400 mg/IVA 250 mg every 12 hours (q12h)<br>* Other names: lumacaftor/ivacaftor;Drug: Placebo<br>* No Active Drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Study Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 8 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | Study Baseline, Through Week 8 |