Trial Outcomes & Findings for A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes) (NCT NCT04058353)
NCT ID: NCT04058353
Last Updated: 2021-07-02
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
271 participants
Primary outcome timeframe
From Baseline Through Week 8
Results posted on
2021-07-02
Participant Flow
A total of 271 participants were enrolled in this study out of which 12 participants discontinued in run-in period. Of 259 participants, 1 participant was randomized but not dosed in the treatment period. Therefore, results are presented for only 258 participants.
This study was conducted in cystic fibrosis (CF) participants aged 12 years or older.
Participant milestones
| Measure |
Control: IVA or TEZ/IVA
Following an IVA (ivacaftor) or TEZ (tezacaftor)/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks.
|
Triple Combination (TC): ELX/TEZ/IVA
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX (elexacaftor) 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
126
|
132
|
|
Overall Study
COMPLETED
|
122
|
131
|
|
Overall Study
NOT COMPLETED
|
4
|
1
|
Reasons for withdrawal
| Measure |
Control: IVA or TEZ/IVA
Following an IVA (ivacaftor) or TEZ (tezacaftor)/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks.
|
Triple Combination (TC): ELX/TEZ/IVA
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX (elexacaftor) 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
1
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Other
|
1
|
0
|
Baseline Characteristics
A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
Baseline characteristics by cohort
| Measure |
Control: IVA or TEZ/IVA
n=126 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
TC: ELX/TEZ/IVA
n=132 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
Total
n=258 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
37.6 years
STANDARD_DEVIATION 14.3 • n=5 Participants
|
37.7 years
STANDARD_DEVIATION 14.7 • n=7 Participants
|
37.7 years
STANDARD_DEVIATION 14.5 • n=5 Participants
|
|
Sex: Female, Male
Female
|
61 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
128 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
65 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
130 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
114 Participants
n=5 Participants
|
117 Participants
n=7 Participants
|
231 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
8 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Collected per Local Regulations
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Aboriginal
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Latin-American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Lebanese
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
110 Participants
n=5 Participants
|
122 Participants
n=7 Participants
|
232 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White, American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
|
68.1 percentage points
STANDARD_DEVIATION 16.4 • n=5 Participants
|
67.1 percentage points
STANDARD_DEVIATION 15.7 • n=7 Participants
|
67.6 percentage points
STANDARD_DEVIATION 16.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: From Baseline Through Week 8Population: Full analysis set (FAS) included all randomized participants who have the intended CF transmembrane conductance regulator (CFTR) allele mutation and received at least 1 dose of study drug in the treatment period. This outcome measure was applicable only for the triple combination arm.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
TC: ELX/TEZ/IVA
n=132 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
TC: ELX/TEZ/IVA
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group
|
3.7 percentage points
Interval 2.8 to 4.6
|
—
|
SECONDARY outcome
Timeframe: From Baseline Through Week 8Population: FAS. This outcome measure was applicable only for the triple combination group.
Sweat samples were collected using an approved collection device.
Outcome measures
| Measure |
TC: ELX/TEZ/IVA
n=132 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
TC: ELX/TEZ/IVA
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group
|
-22.3 millimole per Liter (mmol/L)
Interval -24.5 to -20.2
|
—
|
SECONDARY outcome
Timeframe: From Baseline Through Week 8Population: FAS.
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Outcome measures
| Measure |
TC: ELX/TEZ/IVA
n=126 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
TC: ELX/TEZ/IVA
n=132 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group
|
0.2 percentage points
Interval -0.7 to 1.1
|
3.7 percentage points
Interval 2.8 to 4.6
|
SECONDARY outcome
Timeframe: From Baseline Through Week 8Population: FAS.
Sweat samples were collected using an approved collection device.
Outcome measures
| Measure |
TC: ELX/TEZ/IVA
n=126 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
TC: ELX/TEZ/IVA
n=132 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group
|
0.7 mmol/L
Interval -1.4 to 2.8
|
-22.3 mmol/L
Interval -24.5 to -20.2
|
SECONDARY outcome
Timeframe: From Baseline Through Week 8Population: FAS. This outcome measure was applicable only for the triple combination arm.
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 |
TC: ELX/TEZ/IVA
n=132 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
TC: ELX/TEZ/IVA
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group
|
10.3 units on a scale
Interval 8.0 to 12.7
|
—
|
SECONDARY outcome
Timeframe: From Baseline Through Week 8Population: 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 |
TC: ELX/TEZ/IVA
n=126 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
TC: ELX/TEZ/IVA
n=132 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group
|
1.6 units on a scale
Interval -0.8 to 4.1
|
10.3 units on a scale
Interval 8.0 to 12.7
|
SECONDARY outcome
Timeframe: Day 1 up to Week 12Population: Safety set included all participants who received at least 1 dose of study drug in the treatment period.
Outcome measures
| Measure |
TC: ELX/TEZ/IVA
n=126 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
TC: ELX/TEZ/IVA
n=132 Participants
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Participants With TEAEs
|
83 participants
|
88 participants
|
|
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Participants With SAEs
|
11 participants
|
5 participants
|
Adverse Events
Control: IVA or TEZ/IVA
Serious events: 11 serious events
Other events: 47 other events
Deaths: 0 deaths
TC: ELX/TEZ/IVA
Serious events: 5 serious events
Other events: 35 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Control: IVA or TEZ/IVA
n=126 participants at risk
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
TC: ELX/TEZ/IVA
n=132 participants at risk
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/126 • Day 1 up to Week 12
|
0.76%
1/132 • Day 1 up to Week 12
|
|
Endocrine disorders
Hyperparathyroidism primary
|
0.79%
1/126 • Day 1 up to Week 12
|
0.00%
0/132 • Day 1 up to Week 12
|
|
Hepatobiliary disorders
Cholecystitis
|
0.00%
0/126 • Day 1 up to Week 12
|
0.76%
1/132 • Day 1 up to Week 12
|
|
Infections and infestations
Cellulitis
|
0.00%
0/126 • Day 1 up to Week 12
|
0.76%
1/132 • Day 1 up to Week 12
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
5.6%
7/126 • Day 1 up to Week 12
|
1.5%
2/132 • Day 1 up to Week 12
|
|
Infections and infestations
Pneumonia
|
0.79%
1/126 • Day 1 up to Week 12
|
0.00%
0/132 • Day 1 up to Week 12
|
|
Psychiatric disorders
Anxiety
|
0.79%
1/126 • Day 1 up to Week 12
|
0.00%
0/132 • Day 1 up to Week 12
|
|
Psychiatric disorders
Depression
|
0.79%
1/126 • Day 1 up to Week 12
|
0.00%
0/132 • Day 1 up to Week 12
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.79%
1/126 • Day 1 up to Week 12
|
0.76%
1/132 • Day 1 up to Week 12
|
Other adverse events
| Measure |
Control: IVA or TEZ/IVA
n=126 participants at risk
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
TC: ELX/TEZ/IVA
n=132 participants at risk
Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
1.6%
2/126 • Day 1 up to Week 12
|
5.3%
7/132 • Day 1 up to Week 12
|
|
Gastrointestinal disorders
Diarrhoea
|
6.3%
8/126 • Day 1 up to Week 12
|
3.8%
5/132 • Day 1 up to Week 12
|
|
Gastrointestinal disorders
Nausea
|
7.1%
9/126 • Day 1 up to Week 12
|
1.5%
2/132 • Day 1 up to Week 12
|
|
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis
|
7.9%
10/126 • Day 1 up to Week 12
|
1.5%
2/132 • Day 1 up to Week 12
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/126 • Day 1 up to Week 12
|
6.1%
8/132 • Day 1 up to Week 12
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/126 • Day 1 up to Week 12
|
6.1%
8/132 • Day 1 up to Week 12
|
|
Nervous system disorders
Headache
|
15.1%
19/126 • Day 1 up to Week 12
|
8.3%
11/132 • Day 1 up to Week 12
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
18/126 • Day 1 up to Week 12
|
2.3%
3/132 • Day 1 up to Week 12
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
6.3%
8/126 • Day 1 up to Week 12
|
4.5%
6/132 • Day 1 up to Week 12
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER