Trial Outcomes & Findings for A Phase 3 Study of Tezacaftor (VX-661) in Combination With Ivacaftor (VX-770) in Subjects Aged 12 Years and Older With Cystic Fibrosis (CF), Who Have One F508del-CFTR Mutation and a Second Mutation That Has Been Demonstrated to be Clinically Responsive to Ivacaftor (NCT NCT02412111)
NCT ID: NCT02412111
Last Updated: 2019-01-08
Results Overview
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
156 participants
Primary outcome timeframe
Baseline, Through Week 8
Results posted on
2019-01-08
Participant Flow
The study consisted of 2 periods: an Ivacaftor Run-in Period and an Active Comparator Treatment Period. Participants were randomized in a ratio of 1:1 to receive either VX-661/ivacaftor combination therapy or ivacaftor monotherapy for 8 weeks during the Active Comparator Treatment Period after completion of 4 weeks Ivacaftor Run-in Period.
Participant milestones
| Measure |
Ivacaftor (Run-in Period)
Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks.
|
VX-661 + Ivacaftor (Active Comparator Period)
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
|---|---|---|---|
|
Ivacaftor Run-in Period (4 Weeks)
STARTED
|
156
|
0
|
0
|
|
Ivacaftor Run-in Period (4 Weeks)
COMPLETED
|
153
|
0
|
0
|
|
Ivacaftor Run-in Period (4 Weeks)
NOT COMPLETED
|
3
|
0
|
0
|
|
Active Comparator Period (8 Weeks)
STARTED
|
0
|
76
|
75
|
|
Active Comparator Period (8 Weeks)
Full Analysis Set
|
0
|
76
|
74
|
|
Active Comparator Period (8 Weeks)
COMPLETED
|
0
|
75
|
69
|
|
Active Comparator Period (8 Weeks)
NOT COMPLETED
|
0
|
1
|
6
|
Reasons for withdrawal
| Measure |
Ivacaftor (Run-in Period)
Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks.
|
VX-661 + Ivacaftor (Active Comparator Period)
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
|---|---|---|---|
|
Ivacaftor Run-in Period (4 Weeks)
Did not meet eligibility criteria
|
1
|
0
|
0
|
|
Ivacaftor Run-in Period (4 Weeks)
Participants refused further dosing
|
2
|
0
|
0
|
|
Active Comparator Period (8 Weeks)
Adverse Event
|
0
|
0
|
2
|
|
Active Comparator Period (8 Weeks)
Participants refused further dosing
|
0
|
0
|
1
|
|
Active Comparator Period (8 Weeks)
Lost to Follow-up
|
0
|
0
|
1
|
|
Active Comparator Period (8 Weeks)
Other non-compliance
|
0
|
1
|
0
|
|
Active Comparator Period (8 Weeks)
Other
|
0
|
0
|
2
|
Baseline Characteristics
A Phase 3 Study of Tezacaftor (VX-661) in Combination With Ivacaftor (VX-770) in Subjects Aged 12 Years and Older With Cystic Fibrosis (CF), Who Have One F508del-CFTR Mutation and a Second Mutation That Has Been Demonstrated to be Clinically Responsive to Ivacaftor
Baseline characteristics by cohort
| Measure |
VX-661 + Ivacaftor (Active Comparator Period)
n=76 Participants
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=74 Participants
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
Total
n=150 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
33.0 years
STANDARD_DEVIATION 13.1 • n=5 Participants
|
31.8 years
STANDARD_DEVIATION 11.1 • n=7 Participants
|
32.4 years
STANDARD_DEVIATION 12.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
32 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
76 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
148 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
73 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
145 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Through Week 8Population: Full Analysis Set was defined as all randomized participants who have received at least 1 dose of blinded study drug during the active comparator treatment period. Here "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
VX-661 + Ivacaftor (Active Comparator Period)
n=76 Participants
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=72 Participants
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
|---|---|---|---|
|
Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
|
0.5 Percent predicted of FEV1
Standard Error 0.4
|
0.2 Percent predicted of FEV1
Standard Error 0.4
|
—
|
SECONDARY outcome
Timeframe: Baseline, Through Week 8Population: Full Analysis Set was defined as all randomized participants who have received at least 1 dose of blinded study drug during the active comparator treatment period. Here "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
VX-661 + Ivacaftor (Active Comparator Period)
n=76 Participants
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=72 Participants
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
|---|---|---|---|
|
Relative Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 8
|
1.3 Percent change
Standard Error 0.6
|
0.5 Percent change
Standard Error 0.6
|
—
|
SECONDARY outcome
Timeframe: Baseline, Through Week 8Population: Full Analysis Set was defined as all randomized participants who have received at least 1 dose of blinded study drug during the active comparator treatment period. Here "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome.
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, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Outcome measures
| Measure |
VX-661 + Ivacaftor (Active Comparator Period)
n=76 Participants
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=73 Participants
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
|---|---|---|---|
|
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline Through Week 8
|
0.7 units on a scale
Standard Error 1.3
|
-2.1 units on a scale
Standard Error 1.3
|
—
|
SECONDARY outcome
Timeframe: Baseline, Through Week 8Population: Full Analysis Set was defined as all randomized participants who have received at least 1 dose of blinded study drug during the active comparator treatment period. Here "Overall number of participants analyzed" signifies those participants who were evaluable for this outcome.
Sweat samples were collected using an approved collection device.
Outcome measures
| Measure |
VX-661 + Ivacaftor (Active Comparator Period)
n=74 Participants
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=70 Participants
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
|---|---|---|---|
|
Absolute Change From Baseline in Sweat Chloride Through Week 8
|
-7.9 Millimoles per liter
Standard Error 1.7
|
-2.1 Millimoles per liter
Standard Error 1.8
|
—
|
SECONDARY outcome
Timeframe: Baseline up to Week 16Population: The Safety Set included all participants who received at least 1 dose of study drug during Ivacaftor (Run-in period) and active comparator treatment period.
Outcome measures
| Measure |
VX-661 + Ivacaftor (Active Comparator Period)
n=156 Participants
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=76 Participants
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=75 Participants
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with AEs
|
66 Participants
|
50 Participants
|
54 Participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
2 Participants
|
4 Participants
|
7 Participants
|
SECONDARY outcome
Timeframe: Predose on Week -2 for Run-in period; Pre-dose on Week 2 for Active comparator periodPopulation: Pharmacokinetic (PK) set included participants who received study drug and had PK assessment. Here 'Overall number of participants analyzed' signifies participants who were evaluable for this outcome. "Number Analyzed=0" indicates no participants were analyzed for specified categories because VX-661 was not administered in the specified arms.
Outcome measures
| Measure |
VX-661 + Ivacaftor (Active Comparator Period)
n=143 Participants
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=75 Participants
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=68 Participants
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
|---|---|---|---|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
IVA
|
812 nanogram per milliliter (ng/mL)
Standard Deviation 615
|
1000 nanogram per milliliter (ng/mL)
Standard Deviation 742
|
740 nanogram per milliliter (ng/mL)
Standard Deviation 464
|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
M1-IVA
|
1590 nanogram per milliliter (ng/mL)
Standard Deviation 956
|
1830 nanogram per milliliter (ng/mL)
Standard Deviation 1010
|
1450 nanogram per milliliter (ng/mL)
Standard Deviation 828
|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
VX-661
|
—
|
2520 nanogram per milliliter (ng/mL)
Standard Deviation 1490
|
—
|
|
Trough Plasma Concentrations (Ctrough) of VX-661, VX-661 Metabolites (M1-VX-661), Ivacaftor (IVA) and IVA Metabolite (M1-IVA)
M1-VX-661
|
—
|
4870 nanogram per milliliter (ng/mL)
Standard Deviation 1750
|
—
|
Adverse Events
Ivacaftor (Run-in Period)
Serious events: 2 serious events
Other events: 24 other events
Deaths: 0 deaths
VX-661 + Ivacaftor (Active Comparator Period)
Serious events: 4 serious events
Other events: 25 other events
Deaths: 0 deaths
Ivacaftor Monotherapy (Active Comparator Period)
Serious events: 7 serious events
Other events: 32 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ivacaftor (Run-in Period)
n=156 participants at risk
Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks.
|
VX-661 + Ivacaftor (Active Comparator Period)
n=76 participants at risk
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=75 participants at risk
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
|---|---|---|---|
|
Investigations
Human rhinovirus test positive
|
0.64%
1/156 • Baseline up to Week 16
|
0.00%
0/76 • Baseline up to Week 16
|
0.00%
0/75 • Baseline up to Week 16
|
|
Nervous system disorders
Idiopathic intracranial hypertension
|
0.00%
0/156 • Baseline up to Week 16
|
0.00%
0/76 • Baseline up to Week 16
|
1.3%
1/75 • Baseline up to Week 16
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/156 • Baseline up to Week 16
|
0.00%
0/76 • Baseline up to Week 16
|
1.3%
1/75 • Baseline up to Week 16
|
|
Gastrointestinal disorders
Pancreatitis
|
0.64%
1/156 • Baseline up to Week 16
|
0.00%
0/76 • Baseline up to Week 16
|
0.00%
0/75 • Baseline up to Week 16
|
|
General disorders
Face oedema
|
0.00%
0/156 • Baseline up to Week 16
|
1.3%
1/76 • Baseline up to Week 16
|
0.00%
0/75 • Baseline up to Week 16
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/156 • Baseline up to Week 16
|
1.3%
1/76 • Baseline up to Week 16
|
0.00%
0/75 • Baseline up to Week 16
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/156 • Baseline up to Week 16
|
1.3%
1/76 • Baseline up to Week 16
|
0.00%
0/75 • Baseline up to Week 16
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
0.64%
1/156 • Baseline up to Week 16
|
2.6%
2/76 • Baseline up to Week 16
|
6.7%
5/75 • Baseline up to Week 16
|
|
Infections and infestations
Infective exacerbation of bronchiectasis
|
0.00%
0/156 • Baseline up to Week 16
|
1.3%
1/76 • Baseline up to Week 16
|
0.00%
0/75 • Baseline up to Week 16
|
|
Infections and infestations
Influenza
|
0.00%
0/156 • Baseline up to Week 16
|
1.3%
1/76 • Baseline up to Week 16
|
0.00%
0/75 • Baseline up to Week 16
|
Other adverse events
| Measure |
Ivacaftor (Run-in Period)
n=156 participants at risk
Ivacaftor 150 milligram (mg) tablet orally every 12 hours for 4 weeks.
|
VX-661 + Ivacaftor (Active Comparator Period)
n=76 participants at risk
VX-661 100 mg and ivacaftor 150 mg fixed-dose combination tablet orally once daily in the morning and ivacaftor 150 mg tablet orally once daily in the evening for 8 weeks.
|
Ivacaftor Monotherapy (Active Comparator Period)
n=75 participants at risk
Ivacaftor 150 mg tablet orally every 12 hours as monotherapy for 8 weeks.
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
12/156 • Baseline up to Week 16
|
15.8%
12/76 • Baseline up to Week 16
|
16.0%
12/75 • Baseline up to Week 16
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
5.1%
8/156 • Baseline up to Week 16
|
5.3%
4/76 • Baseline up to Week 16
|
9.3%
7/75 • Baseline up to Week 16
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
1.9%
3/156 • Baseline up to Week 16
|
3.9%
3/76 • Baseline up to Week 16
|
5.3%
4/75 • Baseline up to Week 16
|
|
Nervous system disorders
Dizziness
|
1.3%
2/156 • Baseline up to Week 16
|
5.3%
4/76 • Baseline up to Week 16
|
0.00%
0/75 • Baseline up to Week 16
|
|
General disorders
Fatigue
|
2.6%
4/156 • Baseline up to Week 16
|
6.6%
5/76 • Baseline up to Week 16
|
2.7%
2/75 • Baseline up to Week 16
|
|
Gastrointestinal disorders
Nausea
|
1.9%
3/156 • Baseline up to Week 16
|
0.00%
0/76 • Baseline up to Week 16
|
5.3%
4/75 • Baseline up to Week 16
|
|
Gastrointestinal disorders
Diarrhoea
|
1.3%
2/156 • Baseline up to Week 16
|
5.3%
4/76 • Baseline up to Week 16
|
1.3%
1/75 • Baseline up to Week 16
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
1.3%
2/156 • Baseline up to Week 16
|
7.9%
6/76 • Baseline up to Week 16
|
5.3%
4/75 • Baseline up to Week 16
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.64%
1/156 • Baseline up to Week 16
|
5.3%
4/76 • Baseline up to Week 16
|
8.0%
6/75 • Baseline up to Week 16
|
|
Nervous system disorders
Headache
|
6.4%
10/156 • Baseline up to Week 16
|
7.9%
6/76 • Baseline up to Week 16
|
5.3%
4/75 • Baseline up to Week 16
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PI is free to publish results of the study after (1)first multi-center publication, (2)if 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