Trial Outcomes & Findings for A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F) (NCT NCT03525548)
NCT ID: NCT03525548
Last Updated: 2020-01-27
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
113 participants
Primary outcome timeframe
From Baseline at Week 4
Results posted on
2020-01-27
Participant Flow
A total of 113 participants were enrolled in the study, of which 6 participants were included in the run-in period but were not dosed in TC treatment period. Results are presented for 107 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 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-445/TEZ/IVA TC
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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
|
52
|
55
|
|
Overall Study
COMPLETED
|
52
|
55
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
Baseline characteristics by cohort
| Measure |
TEZ/IVA
n=52 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-445/TEZ/IVA TC
n=55 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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=107 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
27.9 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
28.8 years
STANDARD_DEVIATION 11.5 • n=7 Participants
|
28.4 years
STANDARD_DEVIATION 11.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
28 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
49 Participants
n=5 Participants
|
52 Participants
n=7 Participants
|
101 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
|
52 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
106 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
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
|
60.2 percentage points
STANDARD_DEVIATION 14.4 • n=5 Participants
|
61.6 percentage points
STANDARD_DEVIATION 15.4 • n=7 Participants
|
60.9 percentage points
STANDARD_DEVIATION 14.9 • 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=52 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-445/TEZ/IVA TC
n=55 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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)
|
0.4 percentage points
Standard Error 0.9
|
10.4 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=52 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-445/TEZ/IVA TC
n=55 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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)
|
1.7 millimole per liter (mmol/L)
Standard Error 1.8
|
-43.4 millimole per liter (mmol/L)
Standard Error 1.7
|
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 indicate fewer symptoms and better health-related quality of life.
Outcome measures
| Measure |
TEZ/IVA
n=52 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-445/TEZ/IVA TC
n=55 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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
|
-1.4 units on a scale
Standard Error 2.0
|
16.0 units on a scale
Standard Error 2.0
|
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=52 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-445/TEZ/IVA TC
n=55 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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 by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with AEs
|
33 participants
|
32 participants
|
|
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants with SAEs
|
1 participants
|
2 participants
|
SECONDARY outcome
Timeframe: 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=52 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-445/TEZ/IVA TC
n=55 Participants
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
VX-445: Day 1
|
—
|
NA microgram per milliliter (mcg/mL)
Standard Deviation NA
Data was not reported at the specified time point as all the observations were below the limit of quantitation.
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
VX-445: Week 4
|
—
|
4.84 microgram per milliliter (mcg/mL)
Standard Deviation 2.59
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
TEZ: Day 1
|
1.71 microgram per milliliter (mcg/mL)
Standard Deviation 0.942
|
1.60 microgram per milliliter (mcg/mL)
Standard Deviation 1.03
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
TEZ: Week 4
|
1.48 microgram per milliliter (mcg/mL)
Standard Deviation 0.829
|
1.89 microgram per milliliter (mcg/mL)
Standard Deviation 0.974
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
M1-TEZ: Day 1
|
4.84 microgram per milliliter (mcg/mL)
Standard Deviation 1.71
|
4.76 microgram per milliliter (mcg/mL)
Standard Deviation 1.78
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
M1-TEZ: Week 4
|
4.86 microgram per milliliter (mcg/mL)
Standard Deviation 1.74
|
5.28 microgram per milliliter (mcg/mL)
Standard Deviation 2.04
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
IVA: Day 1
|
0.652 microgram per milliliter (mcg/mL)
Standard Deviation 0.399
|
0.598 microgram per milliliter (mcg/mL)
Standard Deviation 0.428
|
|
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
IVA: Week 4
|
0.530 microgram per milliliter (mcg/mL)
Standard Deviation 0.297
|
0.652 microgram per milliliter (mcg/mL)
Standard Deviation 0.542
|
Adverse Events
TEZ/IVA
Serious events: 1 serious events
Other events: 25 other events
Deaths: 0 deaths
VX-445/TEZ/IVA TC
Serious events: 2 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TEZ/IVA
n=52 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-445/TEZ/IVA TC
n=55 participants at risk
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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.
|
|---|---|---|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
1.9%
1/52 • 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)
|
1.8%
1/55 • 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)
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/52 • 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)
|
1.8%
1/55 • 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=52 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-445/TEZ/IVA TC
n=55 participants at risk
Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 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
Cough
|
7.7%
4/52 • 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)
|
14.5%
8/55 • 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
Haemoptysis
|
9.6%
5/52 • 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)
|
3.6%
2/55 • 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
Oropharyngeal pain
|
0.00%
0/52 • 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)
|
7.3%
4/55 • 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
Sputum increased
|
5.8%
3/52 • 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)
|
5.5%
3/55 • 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
Nasal congestion
|
1.9%
1/52 • 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)
|
5.5%
3/55 • 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
Respiration abnormal
|
0.00%
0/52 • 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)
|
5.5%
3/55 • 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
Nasopharyngitis
|
3.8%
2/52 • 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)
|
7.3%
4/55 • 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
Upper respiratory tract infection
|
3.8%
2/52 • 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)
|
7.3%
4/55 • 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
|
9.6%
5/52 • 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)
|
0.00%
0/55 • 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
|
5.8%
3/52 • 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)
|
3.6%
2/55 • 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
Abdominal pain
|
1.9%
1/52 • 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)
|
5.5%
3/55 • 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
Nausea
|
5.8%
3/52 • 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)
|
1.8%
1/55 • 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
|
7.7%
4/52 • 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)
|
5.5%
3/55 • 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)
|
|
General disorders
Fatigue
|
3.8%
2/52 • 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)
|
5.5%
3/55 • 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