Back to resultsPilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ivacaftor
Placebo-matched-to-ivacaftor tablet
Sponsored by
About this trial
This is an interventional treatment trial for Cystic Fibrosis
Eligibility Criteria
Inclusion Criteria:
- Male or female participants with confirmed diagnosis of CF
- Clinical evidence of residual CFTR function based on any 1 of the following: 1) Clinically documented residual exocrine pancreatic function, 2) Sweat chloride value less than equal to (<=) 80 millimole per liter (mmol/L) at screening, or 3) Age of diagnosis greater than equal to (>=) 12 years and at least 1 copy of a CFTR mutation associated with residual CFTR function or defective mRNA splicing
- FEV1 >= 40 percent (%)
- 12 years of age or older
- Willing to agree to meet the contraception requirements
- Able to swallow tablets
Exclusion Criteria:
- A copy of any of the following CFTR mutations: G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, or G1349D
- Unable to perform spirometry
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1
- Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)
Arm Description
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Outcomes
Primary Outcome Measures
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Secondary Outcome Measures
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment
LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57
LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57
Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a "Washout Period" AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.
Full Information
NCT ID
NCT01685801
First Posted
September 6, 2012
Last Updated
April 30, 2015
Sponsor
Vertex Pharmaceuticals Incorporated
1. Study Identification
Unique Protocol Identification Number
NCT01685801
Brief Title
Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function
Official Title
A Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis, Residual CFTR Function, and FEV1 ≥40% Predicted
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
September 2012 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is a multiple within participant crossover study to evaluate the effect of ivacaftor on lung function in participants aged 12 years and older with cystic fibrosis (CF) who have phenotypic or molecular evidence of residual CF transmembrane conductance regulator (CFTR) function.
Detailed Description
CFTR Mutations associated with residual function or defective messenger ribonucleic acid (mRNA) splicing include the following:
R117H, E56K, P67L, D110E, D110H, R117C, R347H, R352Q, A455E, D579G, S945L, L206W, R1070W, F1074L, D1152H, S1235R, D1270N, 2789+5G->A, 3849+10kbC->T, 3272-26A->G, 711+5G->A, 3120G->A, 1811+1.6kbA->G, 711+3A->G, 1898+3A->G, 1898+1G->A, 1717-1G->A, 1717-8G->A, 1342-2A->C, 405+3A->C, 1716G/A 1811+1G->C, 1898+5G->T, 3850-3T->G, IVS14b+5G->A, 1898+1G->T, 4005+2T->C, 621+3A->G, 621+1G->T.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ivacaftor, Placebo, Ivacaftor, Placebo (IPIP)
Arm Type
Experimental
Arm Description
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Arm Title
Ivacaftor, Placebo, Placebo, Ivacaftor (IPPI)
Arm Type
Experimental
Arm Description
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Arm Title
Placebo, Ivacaftor, Ivacaftor, Placebo (PIIP)
Arm Type
Experimental
Arm Description
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Arm Title
Placebo, Ivacaftor, Placebo, Ivacaftor (PIPI)
Arm Type
Experimental
Arm Description
During the Crossover Period, study drug was administered in 2-week alternating cycles with a minimum of 4-week washout period between Cycle 1 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and Cycle 2 [(Period 1 - Day 1 to 14) (Period 2 - Day 15 to 29)] and between Cycle 2 and the Open-label Period (Day 1 to 57). During the Open-label Period, all participants received ivacaftor.
Intervention Type
Drug
Intervention Name(s)
Ivacaftor
Other Intervention Name(s)
Kalydeco, VX-770
Intervention Description
150 milligram (mg) tablet orally every 12 hours up to 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo-matched-to-ivacaftor tablet
Intervention Description
Orally every 12 hours up to 4 weeks.
Primary Outcome Measure Information:
Title
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) After 2 Weeks of Treatment
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time Frame
Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
Secondary Outcome Measure Information:
Title
Cycle 1 and Cycle 2: Absolute Change From Cycle Baseline In Lung Clearance Index (LCI) After 2 Weeks of Treatment
Description
LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment. Data was to be reported for each cycle (Cycle 1 and Cycle 2) and as per drug treatment, for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time Frame
Cycle 1 baseline, Cycle 1 Day 15 (for Cycle 1 reporting arms); Cycle 2 baseline, Cycle 2 Day 15 (for Cycle 2 reporting arms)
Title
Open-label Period: Absolute Change From Open-label Baseline In Percent Predicted Forced Expiratory Volume In 1 Second (FEV1) at Day 57
Description
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Hankinson and Wang standards were used to calculate percent predicted FEV1 (for age, gender, and height). The Hankinson standard was used for male participants 18 years and older and female participants 16 years and older. The Wang standard was used for male participants aged 12 to 17 years and for female participants aged 12 to 15 years. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time Frame
Open-label Baseline, Open-label Day 57
Title
Open-label Period: Absolute Change From Open-label Baseline In Lung Clearance Index (LCI) at Day 57
Description
LCI is a measure of ventilation inhomogeneity that is derived from a multiple-breath washout test. The LCI was calculated as the number of lung volume turnovers (cumulative expired volume divided by the functional residual capacity [FRC]) required to reduce end-tidal concentration of an inert gas to 1/40th of the starting value. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time Frame
Open-label Baseline, Open-label Day 57
Title
Open-label Period: Absolute Change From Study Baseline In Sweat Chloride at Day 57
Description
Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time Frame
Study Baseline, Open-label Day 57
Title
Open-label Period: Absolute Change From Open-label Baseline In Weight at Day 57
Description
Data was to be reported for overall participants and as per genotype (residual function mutation and mRNA splice site mutation).
Time Frame
Open-label Baseline, Open-label Day 57
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
Adverse events (AEs) that started (or increased in severity) from first dose of study drug through completion of Follow-up were considered TEAEs, with exception that if an AE started during a Washout Period and was beyond 14 days from last dose date of preceding cycle, AE was considered as a "Washout Period" AE, and hence not TEAE. A TEAE was attributed to treatment in which it started or to the treatment in second cycling period of previous Crossover Period if it started during a Washout Period. SAE: medical event or condition, which falls into any of following categories, regardless of its relationship to study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Data was to be reported by drug treatment for double-blind crossover period (Cycle 1 up to Washout Period 2) and open-label period.
Time Frame
From first dose of study drug through completion of follow-up visit (up to 26 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female participants with confirmed diagnosis of CF
Clinical evidence of residual CFTR function based on any 1 of the following: 1) Clinically documented residual exocrine pancreatic function, 2) Sweat chloride value less than equal to (<=) 80 millimole per liter (mmol/L) at screening, or 3) Age of diagnosis greater than equal to (>=) 12 years and at least 1 copy of a CFTR mutation associated with residual CFTR function or defective mRNA splicing
FEV1 >= 40 percent (%)
12 years of age or older
Willing to agree to meet the contraception requirements
Able to swallow tablets
Exclusion Criteria:
A copy of any of the following CFTR mutations: G551D, G178R, S549N, S549R, G551S, G970R, G1244E, S1251N, S1255P, or G1349D
Unable to perform spirometry
An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 4 weeks before Day 1
Ongoing participation in another therapeutic clinical study or prior participation in an investigational drug study within the 30 days prior to screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jerry Nick, MD
Organizational Affiliation
National Jewish Health
Official's Role
Principal Investigator
Facility Information:
City
Denver
State/Province
Colorado
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
31784217
Citation
Nick JA, St Clair C, Jones MC, Lan L, Higgins M; VX12-770-113 Study Team. Ivacaftor in cystic fibrosis with residual function: Lung function results from an N-of-1 study. J Cyst Fibros. 2020 Jan;19(1):91-98. doi: 10.1016/j.jcf.2019.09.013. Epub 2019 Nov 26.
Results Reference
derived
Learn more about this trial
Pilot Study Testing the Effect of Ivacaftor on Lung Function in Subjects With Cystic Fibrosis and Residual CFTR Function
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