Trial Outcomes & Findings for A Phase 2 Study to Evaluate Effects of VX-661/Ivacaftor on Lung and Extrapulmonary Systems in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation (NCT NCT02508207)
NCT ID: NCT02508207
Last Updated: 2021-07-19
Results Overview
MCC was assessed using an imaging technique that enables the tracking of mucus within the airways. MCC was expressed as the percentage of whole-lung clearance through 60 minutes at Baseline and Day 28.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
34 participants
Primary outcome timeframe
Baseline, Day 28
Results posted on
2021-07-19
Participant Flow
Participant milestones
| Measure |
Placebo
Participants received placebo matched to tezacaftor (TEZ)/ivacaftor (IVA) fixed dose combination (FDC) tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.
|
TEZ/IVA
Participants received 100 milligram (mg) TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.
|
|---|---|---|
|
Overall Study
STARTED
|
7
|
27
|
|
Overall Study
COMPLETED
|
7
|
27
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Phase 2 Study to Evaluate Effects of VX-661/Ivacaftor on Lung and Extrapulmonary Systems in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
Baseline characteristics by cohort
| Measure |
Placebo
n=7 Participants
Participants received placebo matched to TEZ/IVA FDC tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.
|
TEZ/IVA
n=27 Participants
Participants received 100 mg TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.
|
Total
n=34 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38 years
STANDARD_DEVIATION 11.8 • n=99 Participants
|
32.1 years
STANDARD_DEVIATION 8.6 • n=107 Participants
|
33.4 years
STANDARD_DEVIATION 9.5 • n=206 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=99 Participants
|
27 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=99 Participants
|
27 Participants
n=107 Participants
|
34 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Mucociliary Clearance (MCC): Percentage of Whole-lung Clearance
|
15.3 percentage of whole-lung clearance
STANDARD_DEVIATION 15.1 • n=99 Participants
|
18.4 percentage of whole-lung clearance
STANDARD_DEVIATION 11.3 • n=107 Participants
|
17.8 percentage of whole-lung clearance
STANDARD_DEVIATION 12.0 • n=206 Participants
|
|
Small-bowel Area Under the Curve (AUC) Over 1-minute Mean pH Increments
|
5.8 pH minutes
STANDARD_DEVIATION 0.4 • n=99 Participants
|
5.7 pH minutes
STANDARD_DEVIATION 0.6 • n=107 Participants
|
5.8 pH minutes
STANDARD_DEVIATION 0.6 • n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 28Population: The Full Analysis Set (FAS) included all randomized participants who carry the relevant cystic fibrosis transmembrane conductance regulator (CFTR) allele and received at least 1 dose of study drug.
MCC was assessed using an imaging technique that enables the tracking of mucus within the airways. MCC was expressed as the percentage of whole-lung clearance through 60 minutes at Baseline and Day 28.
Outcome measures
| Measure |
Placebo
n=7 Participants
Participants received placebo matched to TEZ/IVA FDC tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.
|
TEZ/IVA
n=27 Participants
Participants received 100 mg TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.
|
|---|---|---|
|
Absolute Change From Baseline in Mucociliary Clearance (MCC) at Day 28
|
-0.5 percentage of whole-lung clearance
Standard Deviation 11.2
|
-0.9 percentage of whole-lung clearance
Standard Deviation 12.1
|
SECONDARY outcome
Timeframe: Baseline, Day 28Population: The FAS was used.
Percent predicted FEV1 is the ratio of FEV1 to the predicted FEV1, expressed as a percentage. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
Placebo
n=7 Participants
Participants received placebo matched to TEZ/IVA FDC tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.
|
TEZ/IVA
n=27 Participants
Participants received 100 mg TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.
|
|---|---|---|
|
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28
|
-0.4 percentage of predicted FEV1
Standard Deviation 5.9
|
2.4 percentage of predicted FEV1
Standard Deviation 3.1
|
SECONDARY outcome
Timeframe: Baseline, Day 29Population: The FAS was used. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Absolute change from Baseline in small bowel AUC over 1-minute mean pH increments through 30 minutes at Day 29 was assessed.
Outcome measures
| Measure |
Placebo
n=6 Participants
Participants received placebo matched to TEZ/IVA FDC tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.
|
TEZ/IVA
n=23 Participants
Participants received 100 mg TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.
|
|---|---|---|
|
Absolute Change From Baseline in Small-bowel Area Under the Curve (AUC) Over 1-minute Mean pH Increments at Day 29
|
0.3 pH minutes
Standard Deviation 0.5
|
-0.2 pH minutes
Standard Deviation 0.8
|
SECONDARY outcome
Timeframe: Baseline, Day 29Population: The FAS was used. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Outcome measures
| Measure |
Placebo
n=7 Participants
Participants received placebo matched to TEZ/IVA FDC tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.
|
TEZ/IVA
n=23 Participants
Participants received 100 mg TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.
|
|---|---|---|
|
Absolute Change From Baseline in Sweat Chloride at Day 29
|
-0.2 millimoles per liter
Standard Deviation 6.0
|
-8.4 millimoles per liter
Standard Deviation 9.2
|
SECONDARY outcome
Timeframe: Baseline up to Day 57Population: The Safety Set included all participants who received at least 1 dose of study drug.
Outcome measures
| Measure |
Placebo
n=7 Participants
Participants received placebo matched to TEZ/IVA FDC tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.
|
TEZ/IVA
n=27 Participants
Participants received 100 mg TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with AEs
|
2 Participants
|
24 Participants
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
TEZ/IVA
Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=7 participants at risk
Participants received placebo matched to TEZ/IVA FDC tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days.
|
TEZ/IVA
n=27 participants at risk
Participants received 100 mg TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days.
|
|---|---|---|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
0.00%
0/7 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
25.9%
7/27 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/7 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
29.6%
8/27 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/7 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
11.1%
3/27 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
0.00%
0/7 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
7.4%
2/27 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/7 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
11.1%
3/27 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
|
Renal and urinary disorders
Renal impairment
|
14.3%
1/7 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
0.00%
0/27 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.3%
1/7 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
0.00%
0/27 • Baseline up to Day 57: 29 days of dosing + 28 days of safety follow up
Other adverse events table reports the participants with adverse events that exceed a frequency threshold of at least 5% within any arm of the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PI is free to publish results of the study after (1) the first multi-center publication, (2) if the sponsor elects not to publish the results, or (3) 18 months after close of the study, whichever occurs first. Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 45 days (which may be extended under certain circumstances related to protection of intellectual property); the sponsor cannot require changes to the proposed publications.
- Publication restrictions are in place
Restriction type: OTHER