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

• ClinicalTrials.gov Identifier: NCT03061331
• Recruitment Status: Completed
• First Posted: February 23, 2017
• Results First Posted: October 2, 2018
• Last Update Posted: October 2, 2018
• Sponsor: Vertex Pharmaceuticals Incorporated
• Information provided by (Responsible Party): Vertex Pharmaceuticals Incorporated

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cystic Fibrosis	Drug: LUM/IVA; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: January 31, 2017
• Actual Primary Completion Date: September 6, 2017
• Actual Study Completion Date: October 4, 2017

Arms and Interventions

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 Name: 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 Name: lumacaftor/ivacaftor; Drug: Placebo; No Active Drug

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

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

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

Contacts and Locations

Locations

Netherlands

HagaZiekenhuis

Den Haag, Netherlands

University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis

Heidelberglaan, Netherlands

Sponsors and Collaborators

Vertex Pharmaceuticals Incorporated

  Study Documents (Full-Text)

Documents provided by Vertex Pharmaceuticals Incorporated:

Study Protocol  [PDF] February 17, 2017

Statistical Analysis Plan  [PDF] September 7, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT03061331
• Other Study ID Numbers: VX15-809-111; 2016-001585-29 ( EudraCT Number )
• First Posted: February 23, 2017
• Results First Posted: October 2, 2018
• Last Update Posted: October 2, 2018
• Last Verified: September 2018

• 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

Additional relevant MeSH terms:

Cystic Fibrosis; Fibrosis; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Ivacaftor; Chloride Channel Agonists; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action