Trial Outcomes & Findings for A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F) (NCT NCT03460990)
NCT ID: NCT03460990
Last Updated: 2019-10-17
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
116 participants
Primary outcome timeframe
From Baseline at Week 4
Results posted on
2019-10-17
Participant Flow
A total of 116 participants were enrolled in the study, of which 5 participants were included in the run-in period but were not dosed in TC treatment period. Results are presented for 111 participants dosed in the TC treatment period.
This study was conducted in participants with cystic fibrosis (CF) aged 12 years or older.
Participant milestones
| Measure |
TEZ/IVA
Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period.
|
VX-659/TEZ/IVA TC
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
|---|---|---|
|
Overall Study
STARTED
|
57
|
54
|
|
Overall Study
COMPLETED
|
57
|
54
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of VX-659 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
Baseline characteristics by cohort
| Measure |
TEZ/IVA
n=57 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received TEZ 100 mg/IVA 150 mg as FDC tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
VX-659/TEZ/IVA TC
n=54 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
Total
n=111 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
26.2 years
STANDARD_DEVIATION 9.1 • n=5 Participants
|
28.3 years
STANDARD_DEVIATION 9.6 • n=7 Participants
|
27.2 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
56 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
108 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
56 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
110 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
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Forced Expiratory Volume in 1 Second (ppFEV1)
|
62.9 percentage points
STANDARD_DEVIATION 14.9 • n=5 Participants
|
62.0 percentage points
STANDARD_DEVIATION 14.8 • n=7 Participants
|
62.4 percentage points
STANDARD_DEVIATION 14.8 • n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline at Week 4Population: Full analysis set (FAS) included all randomized participants who carried the intended CF transmembrane conductance regulator gene (CFTR) allele mutation and received at least 1 dose of study drug in the TC Treatment Period.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
TEZ/IVA
n=57 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received TEZ 100 mg/IVA 150 mg as FDC tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
VX-659/TEZ/IVA TC
n=54 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
|---|---|---|
|
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
|
0.3 percentage points
Standard Error 0.9
|
10.2 percentage points
Standard Error 0.9
|
SECONDARY outcome
Timeframe: From Baseline at Week 4Population: FAS.
Sweat samples were collected using an approved collection device.
Outcome measures
| Measure |
TEZ/IVA
n=57 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received TEZ 100 mg/IVA 150 mg as FDC tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
VX-659/TEZ/IVA TC
n=54 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
|---|---|---|
|
Absolute Change in Sweat Chloride (SwCl)
|
1.5 millimole per liter (mmol/L)
Standard Error 1.8
|
-47.2 millimole per liter (mmol/L)
Standard Error 1.9
|
SECONDARY outcome
Timeframe: From Baseline at Week 4Population: FAS.
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 |
TEZ/IVA
n=57 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received TEZ 100 mg/IVA 150 mg as FDC tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
VX-659/TEZ/IVA TC
n=54 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
|---|---|---|
|
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
|
3.0 units on a scale
Standard Error 1.7
|
16.5 units on a scale
Standard Error 1.7
|
SECONDARY outcome
Timeframe: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)Population: Safety set included all participants who received at least 1 dose of study drug in the TC treatment period.
Outcome measures
| Measure |
TEZ/IVA
n=57 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received TEZ 100 mg/IVA 150 mg as FDC tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
VX-659/TEZ/IVA TC
n=54 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
|---|---|---|
|
Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with AEs
|
31 participants
|
33 participants
|
|
Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
0 participants
|
2 participants
|
SECONDARY outcome
Timeframe: From Day 1 and Week 4Population: Pharmacokinetic analysis set included all participants who received at least 1 dose of study drug in the TC treatment period. Here "Number analyzed" signifies those participants who were evaluable at specified time points.
Outcome measures
| Measure |
TEZ/IVA
n=57 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received TEZ 100 mg/IVA 150 mg as FDC tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
VX-659/TEZ/IVA TC
n=54 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
|---|---|---|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Week 4: IVA
|
722 nanogram per milliliter (ng/mL)
Standard Deviation 642
|
401 nanogram per milliliter (ng/mL)
Standard Deviation 211
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Week 4: VX-659
|
—
|
720 nanogram per milliliter (ng/mL)
Standard Deviation 589
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Day 1: TEZ
|
1780 nanogram per milliliter (ng/mL)
Standard Deviation 832
|
1590 nanogram per milliliter (ng/mL)
Standard Deviation 1020
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Week 4: TEZ
|
1730 nanogram per milliliter (ng/mL)
Standard Deviation 885
|
1280 nanogram per milliliter (ng/mL)
Standard Deviation 594
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Day 1: M1-TEZ
|
5170 nanogram per milliliter (ng/mL)
Standard Deviation 1620
|
4840 nanogram per milliliter (ng/mL)
Standard Deviation 1860
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Week 4: M1-TEZ
|
5010 nanogram per milliliter (ng/mL)
Standard Deviation 1810
|
4730 nanogram per milliliter (ng/mL)
Standard Deviation 1380
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Day 1: IVA
|
717 nanogram per milliliter (ng/mL)
Standard Deviation 616
|
563 nanogram per milliliter (ng/mL)
Standard Deviation 400
|
Adverse Events
TEZ/IVA
Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths
VX-659/TEZ/IVA TC
Serious events: 2 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TEZ/IVA
n=57 participants at risk
Following a run-in period of 4 weeks with TEZ/IVA, participants received TEZ 100 mg/IVA 150 mg as FDC tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
VX-659/TEZ/IVA TC
n=54 participants at risk
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
|---|---|---|
|
Psychiatric disorders
Depression
|
0.00%
0/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
1.9%
1/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
1.9%
1/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
1.9%
1/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
Other adverse events
| Measure |
TEZ/IVA
n=57 participants at risk
Following a run-in period of 4 weeks with TEZ/IVA, participants received TEZ 100 mg/IVA 150 mg as FDC tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
VX-659/TEZ/IVA TC
n=54 participants at risk
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
0.00%
0/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
16.7%
9/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.3%
3/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
7.4%
4/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
|
Investigations
Alanine aminotransferase increased
|
3.5%
2/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
5.6%
3/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
|
Investigations
Aspartate aminotransferase increased
|
1.8%
1/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
5.6%
3/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
|
Investigations
C-reactive protein increased
|
0.00%
0/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
7.4%
4/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
15.8%
9/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
3.7%
2/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
|
Nervous system disorders
Headache
|
8.8%
5/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
5.6%
3/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/57 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
7.4%
4/54 • From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER