Study of VX-661 Alone and in Combination With Ivacaftor in Subjects Homozygous or Heterozygous to the F508del-Cystic Fibrosis Transmembrane Conductance Regulator(CFTR) Mutation

Cystic Fibrosis Clinical Trial

Official title:

A Phase 2, Multicenter, Double-Blinded, Placebo Controlled Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-661 Monotherapy and VX-661/Ivacaftor Cotherapy in Subjects With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01531673
• Other study ID #: VX11-661-101
• Secondary ID: 2011-003821-93
• Status: Completed
• Phase: Phase 2
• First received: February 1, 2012
• Last updated: March 14, 2018
• Start date: February 2012
• Est. completion date: March 2014

Study information

• Verified date: March 2018
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) effects of VX-661 alone and when coadministered with ivacaftor in participants with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del-CFTR mutation.

Description:

This is a Phase 2, randomized, multicenter, double-blinded, placebo-controlled, study of VX-661 monotherapy, and VX-661/ivacaftor co-therapy in participants with CF who are homozygous or heterozygous for the F508del CFTR mutation.

This study is separated into seven groups: Group 1-7, respectively. Approximately 180 participants were randomized in a ratio of 4:1; active drug to matching placebo in each group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: March 2014
• Est. primary completion date: March 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Male or female with confirmed diagnosis of CF

• Must have the F508del-CFTR gene mutation in both alleles (Groups 1, 2, 3, 4, 5, 6). Group 7 participants must have the F508del-CFTR mutation on 1 allele, and gating mutation G551D on the second allele and have been on their physician prescribed 150 mg KalydecoTM q12h (commercially available ivacaftor) for at least 28 days at the Screening Visit.

• Forced expiratory volume in 1 second(FEV1) 40% to 90% (inclusive) of predicted normal for age, gender, and height (Knudson standards) at screening

• Weight >40 kg and BMI >18.5

• Participants of child-bearing potential and who are sexually active must meet the contraception requirements.

Exclusion Criteria:

• History of any illness 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 participant.

• An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Study Day 1.

• History of solid organ or hematological transplantation

• Participation in a clinical study involving administration of either an investigational or a marketed drug within 30 days or 5 terminal half-lives (whichever is longer) before screening

• History of alcohol, medication, or illicit drug abuse within 1 year prior to screening

• Pregnant, breast-feeding, or not willing to follow contraception requirements

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Drug:
• VX-661

• Ivacaftor

• Placebo matched to VX-661

• Placebo matched to ivacaftor

Locations

Country	Name	City	State
Canada	Vertex Investigational Site	Calgary	Alberta
Canada	Vertex Investigational Site	Halifax	Nova Scotia
Canada	Vertex Investigational Site	Toronto	Ontario
Canada	Vertex Investigational Site	Vancouver	British Columbia
Germany	Vertex Investigational Site	Berlin
Germany	Vertex Investigational Site	Bochum
Germany	Vertex Investigational Site	Erlangen	Bayern
Germany	Vertex Investigational Site	Frankfurt	Hessen
Germany	Vertex Investigational Site	Hannover	Niedersachsen
Germany	Vertex Investigational Site	Jena
Germany	Vertex Investigational Site	Koeln	Nordrhein Westfalen
Germany	Vertex Investigational Site	Munich
United Kingdom	Vertex Investigational Site	Cambridge	Cambridgeshire
United Kingdom	Vertex Investigational Site	Cardiff	Vale Of Glamorgen
United Kingdom	Vertex Investigational Site	London	Greater London
United Kingdom	Vertex Investigational Site	Manchester	Greater Manchester
United Kingdom	Vertex Investigational Site	Southhampton	Hampshire
United States	Vertex Investigational Site	Birmingham	Alabama
United States	Vertex Investigational Site	Boise	Idaho
United States	Vertex Investigational Site	Boston	Massachusetts
United States	Vertex Investigational Site	Burlington	Vermont
United States	Vertex Investigational Site	Chapel Hill	North Carolina
United States	Vertex Investigational Site	Charleston	South Carolina
United States	Vertex Investigational Site	Chicago	Illinois
United States	Vertex Investigational Site	Cincinnati	Ohio
United States	Vertex Investigational Site	Columbus	Ohio
United States	Vertex Investigational Site	Grand Rapids	Michigan
United States	Vertex Investigational Site	Hershey	Pennsylvania
United States	Vertex Investigational Site	Kansas City	Missouri
United States	Vertex Investigational Site	Long Branch	New Jersey
United States	Vertex Investigational Site	New Hyde Park	New York
United States	Vertex Investigational Site	Oakland	California
United States	Vertex Investigational Site	Oklahoma City	Oklahoma
United States	Vertex Investigational Site	Pittsburgh	Pennsylvania
United States	Vertex Investigational Site	Salt Lake City	Utah
United States	Vertex Investigational Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Canada,  Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety as Determined by Adverse Events (AEs)	An AE is defined as any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the Informed Consent Form is signed. AE includes serious as well as non-serious AEs. Serious Adverse Event (SAE) is any AE that results in any of the following: death; life-threatening condition; inpatient hospitalization or prolongation of hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; or other important medical event. Treatment-emergent adverse events are defined as adverse events that were reported or worsened on or after start of study drug through the Follow-up Visit (28 days after last dose of study drug) or premature discontinuation.	Start of study drug through the Follow-up Visit (Up to Day 56)
Primary	Change in Sweat Chloride From Baseline Through Study Day 28 for Group 1-5b	Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.	Baseline through Day 28
Primary	Change in Sweat Chloride From Baseline Through Study Day 28 for Group 6	Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.	Baseline through Day 28
Primary	Change in Sweat Chloride From Baseline Through Study Day 28 for Group 7	Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.	Baseline through Day 28
Secondary	Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 1-5b	Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.	Baseline, Day 7, Day 14, Day 21, Day 28
Secondary	Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 6	Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.	Baseline, Day 7, Day 14, Day 21, Day 28
Secondary	Change in Sweat Chloride From Baseline to Each Visit up to Study Day 28 for Group 7	Sweat samples were collected using an approved collection device. Baseline was defined as the most recent non-missing measurement collected before initial administration of study drug.	Baseline, Day 7, Day 14, Day 21, Day 28
Secondary	Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	Baseline, Day 7, Day 14, Day 21, Day 28
Secondary	Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.	Baseline, Day 7, Day 14, Day 21, Day 28
Secondary	Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	Baseline, Day 7, Day 14, Day 21, Day 28
Secondary	Change in FEV1 (Liter [L]) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	Baseline, Day 7, Day 14, Day 21, Day 28
Secondary	Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.	Baseline, Day 7, Day 14, Day 21, Day 28
Secondary	Change in FEV1 (L) From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.	Baseline, Day 7, Day 14, Day 21, Day 28
Secondary	Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 1-5b	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.	Baseline, Day 14, Day 28
Secondary	Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 6	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. As per planned analysis, participants who received placebo in Group 4 and 6 were combined and compared with Group 6.	Baseline, Day 14, Day 28
Secondary	Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline to Each Visit and From Baseline Through Study Day 28 for Group 7	The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.	Baseline, Day 14, Day 28
Secondary	Area Under the Concentration Versus Time Curve From Time 0 to 24 Hours (AUC0-24h) of VX-661 After Administration of VX-661 Monotherapy	Participants who received VX-661 monotherapy (Group 1, 2a, 3a and 5a) were analyzed for this outcome measure. PK analysis (AUC0-24h) was not planned for placebo reporting arms.	Day 28
Secondary	AUC0-24h of VX-661 and AUC0-12h of Ivacaftor After Administration of VX-661 in Combination With Ivacaftor	Participants who received VX-661 in combination with Ivacaftor (Group 2b, 3b, 4, 5b, 6a, 6d and 7) were analyzed for this outcome measure. PK analysis was not planned for placebo reporting arms.	Day 28