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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: LUM/IVA; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Den Haag, Netherlands
    • Hagaziekenhuis
  • Heidelberglaan, Netherlands
    • University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Vertex Pharmaceuticals Incorporated

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2017
• Primary Completion (Actual): September 6, 2017
• Study Completion (Actual): October 4, 2017

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 17, 2017
• First Posted (Actual): February 23, 2017

Study Record Updates

• Last Update Posted (Actual): October 2, 2018
• Last Update Submitted That Met QC Criteria: September 6, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Ivacaftor
• Other Study ID Numbers: VX15-809-111; 2016-001585-29 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes