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A Phase 3 Study of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

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ClinicalTrials.gov Identifier: NCT03447249
Recruitment Status : Completed
First Posted : February 27, 2018
Results First Posted : March 13, 2020
Last Update Posted : March 13, 2020
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: VX-659/TEZ/IVA
Drug: IVA
Drug: Placebo
Enrollment 385
Recruitment Details A total of 385 participants were enrolled in the study, of which 3 participants were enrolled but were not dosed in the TC treatment period. Results are presented for 382 participants dosed in the TC treatment period.
Pre-assignment Details This study was conducted in participants with cystic fibrosis (CF) aged 12 years or older.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period. Participants who received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
Period Title: Overall Study
Started 190 192
Safety Set [1] 189 193
Completed 185 192
Not Completed 5 0
Reason Not Completed
Adverse Event             1             0
Withdrawal of consent (not due to AE)             1             0
Other             3             0
[1]
Based on actual treatment received.
Arm/Group Title Placebo VX-659/TEZ/IVA TC Total
Hide Arm/Group Description Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period. Participants who 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 24 weeks in the TC treatment period. Total of all reporting groups
Overall Number of Baseline Participants 190 192 382
Hide Baseline Analysis Population Description
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.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 190 participants 192 participants 382 participants
27.1  (10.0) 26.7  (9.8) 26.9  (9.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 190 participants 192 participants 382 participants
Female
83
  43.7%
85
  44.3%
168
  44.0%
Male
107
  56.3%
107
  55.7%
214
  56.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 190 participants 192 participants 382 participants
Hispanic or Latino
7
   3.7%
6
   3.1%
13
   3.4%
Not Hispanic or Latino
181
  95.3%
184
  95.8%
365
  95.5%
Unknown or Not Reported
2
   1.1%
2
   1.0%
4
   1.0%
Race  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 190 participants 192 participants 382 participants
White
187
  98.4%
188
  97.9%
375
  98.2%
Black or African American
1
   0.5%
2
   1.0%
3
   0.8%
Both White and Black/African American
2
   1.1%
2
   1.0%
4
   1.0%
Forced Expiratory Volume in 1 Second (ppFEV1)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage points
Number Analyzed 190 participants 192 participants 382 participants
60.4  (14.5) 60.7  (15.4) 60.6  (14.9)
[1]
Measure Description: FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
1.Primary Outcome
Title Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame From Baseline at Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all participants in the Full Analysis Set (all randomized participants who carried the intended CFTR allele mutation and received at least 1 dose of study drug) who completed the Week 4 Visit or were randomized at least 28 days before the data cutoff date.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 190 192
Least Squares Mean (Standard Error)
Unit of Measure: percentage points
-1.0  (0.6) 13.0  (0.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VX-659/TEZ/IVA TC
Comments The data presented for Primary endpoint was based on interim analysis at Week 4.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model for repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Mean Difference
Estimated Value 14.0
Confidence Interval (2-Sided) 95%
12.4 to 15.7
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS) included all randomized participants who carried the intended CFTR allele mutation and received at least 1 dose of study drug in the TC Treatment Period.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 190 192
Least Squares Mean (Standard Error)
Unit of Measure: percentage points
-0.8  (0.6) 13.4  (0.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VX-659/TEZ/IVA TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model for repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 14.2
Confidence Interval (2-Sided) 95%
12.6 to 15.7
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Number of Pulmonary Exacerbations (PEx)
Hide Description Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 190 192
Measure Type: Number
Unit of Measure: pulmonary exacerbation events
116 17
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VX-659/TEZ/IVA TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
0.09 to 0.24
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Absolute Change in Sweat Chloride (SwCl)
Hide Description Sweat samples were collected using an approved collection device.
Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 190 192
Least Squares Mean (Standard Error)
Unit of Measure: millimole per liter (mmol/L)
-0.1  (1.0) -44.6  (0.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VX-659/TEZ/IVA TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model for repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -44.6
Confidence Interval (2-Sided) 95%
-47.2 to -41.9
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
Hide Description 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.
Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 190 192
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.5  (1.1) 18.6  (1.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VX-659/TEZ/IVA TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model for repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 20.1
Confidence Interval (2-Sided) 95%
17.2 to 23.0
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Absolute Change in Body Mass Index (BMI)
Hide Description BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
Time Frame From Baseline at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 190 192
Least Squares Mean (Standard Error)
Unit of Measure: kilogram per meter square (kg/m^2)
-0.05  (0.07) 1.06  (0.07)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VX-659/TEZ/IVA TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model for repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.11
Confidence Interval (2-Sided) 95%
0.91 to 1.31
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Absolute Change in Sweat Chloride
Hide Description Sweat samples were collected using an approved collection device.
Time Frame From Baseline at Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 190 192
Least Squares Mean (Standard Error)
Unit of Measure: mmol/L
0.0  (1.0) -43.3  (1.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VX-659/TEZ/IVA TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model for repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -43.4
Confidence Interval (2-Sided) 95%
-46.3 to -40.5
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Absolute Change in Cystic Fibrosis Questionnaire Revised (CFQ-R) Respiratory Domain Score
Hide Description 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.
Time Frame From Baseline at Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who received VX-659 240 mg/TEZ 100 mg/IVA 150 mg as fixed-dose combination (FDC) tablets in the morning and IVA 150 mg as mono tablet in the evening for 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 190 192
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.1  (1.2) 18.0  (1.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VX-659/TEZ/IVA TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effects model for repeated measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 17.9
Confidence Interval (2-Sided) 95%
14.5 to 21.3
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Time-to-first Pulmonary Exacerbation (PEx)
Hide Description Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.
Time Frame From Baseline through Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 190 192
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Median and 95% confidence interval could not be estimated because less than 50% of participants had events.
10.Secondary Outcome
Title Absolute Change in BMI Z-score for Participants <=20 Years of Age at Baseline
Hide Description BMI was defined as weight in kg divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. BMI, adjusted for age and sex, was analyzed as BMI-for-age z-score. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean. Higher values are indicative of higher BMI.
Time Frame From Baseline at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS. Here "Overall Number of Participants Analyzed" signifies those participants who were <=20 years of age at Baseline.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 59 58
Least Squares Mean (Standard Error)
Unit of Measure: kg/m^2
-0.08  (0.05) 0.31  (0.05)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VX-659/TEZ/IVA TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.24 to 0.54
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Absolute Change in Body Weight
Hide Description [Not Specified]
Time Frame From Baseline at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 190 192
Least Squares Mean (Standard Error)
Unit of Measure: kg
0.1  (0.2) 3.3  (0.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, VX-659/TEZ/IVA TC
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
2.7 to 3.8
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description [Not Specified]
Time Frame 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 28 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Adverse events are presented as per Safety Set. Group assignments for participants in the Safety Set were based on actual treatment received, such that 1 participant assigned to Placebo group who inadvertently received one or more doses of VX-659/TEZ/IVA TC regimen was included in VX-659/TEZ/IVA TC group for the purpose of safety analysis.
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period.
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 189 193
Measure Type: Number
Unit of Measure: participants
Participants with TEAEs 175 173
Participants with Serious TEAEs 58 11
13.Secondary Outcome
Title Observed Pre-dose Concentration (Ctrough) of VX-659, TEZ, M1-TEZ, and IVA
Hide Description [Not Specified]
Time Frame Pre-dose on Week 4, 8, 12, and 16
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) set included all randomized participants who carried the intended CFTR allele mutation and received at least 1 dose of study drug in the TC Treatment Period. Here "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified time points.
Arm/Group Title VX-659/TEZ/IVA TC
Hide Arm/Group Description:
Participants who 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 24 weeks in the TC treatment period.
Overall Number of Participants Analyzed 192
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
VX-659 (Week 4) Number Analyzed 150 participants
662  (528)
VX-659 (Week 8) Number Analyzed 148 participants
764  (1520)
VX-659 (Week 12) Number Analyzed 144 participants
614  (519)
VX-659 (Week 16) Number Analyzed 162 participants
638  (521)
TEZ (Week 4) Number Analyzed 150 participants
1220  (645)
TEZ (Week 8) Number Analyzed 148 participants
1390  (1250)
TEZ (Week 12) Number Analyzed 142 participants
1290  (766)
TEZ (Week 16) Number Analyzed 161 participants
1220  (654)
M1-TEZ (Week 4) Number Analyzed 150 participants
4380  (1560)
M1-TEZ (Week 8) Number Analyzed 148 participants
4580  (1480)
M1-TEZ (Week 12) Number Analyzed 142 participants
4580  (1530)
M1-TEZ (Week 16) Number Analyzed 161 participants
4420  (1520)
IVA (Week 4) Number Analyzed 150 participants
442  (277)
IVA (Week 8) Number Analyzed 148 participants
548  (1100)
IVA (Week 12) Number Analyzed 142 participants
429  (327)
IVA (Week 16) Number Analyzed 161 participants
416  (303)
Time Frame 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 28 weeks)
Adverse Event Reporting Description Adverse events are presented as per Safety Set. Group assignments for participants in the Safety Set were based on actual treatment received, such that 1 participant assigned to Placebo group who inadvertently received one or more doses of VX-659/TEZ/IVA TC regimen was included in VX-659/TEZ/IVA TC group for the purpose of safety analysis.
 
Arm/Group Title Placebo VX-659/TEZ/IVA TC
Hide Arm/Group Description Participants who received placebo matched to VX-659/TEZ/IVA in the morning and placebo matched to IVA in the evening for 24 weeks in the TC treatment period. Participants who 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 24 weeks in the TC treatment period.
All-Cause Mortality
Placebo VX-659/TEZ/IVA TC
Affected / at Risk (%) Affected / at Risk (%)
Total   0/189 (0.00%)   0/193 (0.00%) 
Hide Serious Adverse Events
Placebo VX-659/TEZ/IVA TC
Affected / at Risk (%) Affected / at Risk (%)
Total   58/189 (30.69%)   11/193 (5.70%) 
Cardiac disorders     
Pericardial effusion  1  1/189 (0.53%)  0/193 (0.00%) 
Congenital, familial and genetic disorders     
Cystic fibrosis related diabetes  1  0/189 (0.00%)  1/193 (0.52%) 
Right-to-left cardiac shunt  1  1/189 (0.53%)  0/193 (0.00%) 
Gastrointestinal disorders     
Small intestinal obstruction  1  1/189 (0.53%)  0/193 (0.00%) 
Constipation  1  0/189 (0.00%)  1/193 (0.52%) 
Distal intestinal obstruction syndrome  1  2/189 (1.06%)  0/193 (0.00%) 
Gastritis  1  0/189 (0.00%)  1/193 (0.52%) 
Nausea  1  1/189 (0.53%)  0/193 (0.00%) 
Vomiting  1  1/189 (0.53%)  0/193 (0.00%) 
Hepatobiliary disorders     
Bile duct stone  1  0/189 (0.00%)  1/193 (0.52%) 
Infections and infestations     
Infective pulmonary exacerbation of cystic fibrosis  1  45/189 (23.81%)  3/193 (1.55%) 
Influenza  1  0/189 (0.00%)  1/193 (0.52%) 
Lower respiratory tract infection bacterial  1  2/189 (1.06%)  0/193 (0.00%) 
Bronchitis  1  1/189 (0.53%)  0/193 (0.00%) 
Dysentery  1  0/189 (0.00%)  1/193 (0.52%) 
Infective exacerbation of bronchiectasis  1  1/189 (0.53%)  0/193 (0.00%) 
Respiratory tract infection bacterial  1  0/189 (0.00%)  1/193 (0.52%) 
Pneumonia  1  1/189 (0.53%)  0/193 (0.00%) 
Vascular device infection  1  1/189 (0.53%)  0/193 (0.00%) 
Injury, poisoning and procedural complications     
Intentional overdose  1  0/189 (0.00%)  1/193 (0.52%) 
Pneumothorax traumatic  1  1/189 (0.53%)  0/193 (0.00%) 
Investigations     
Forced expiratory volume decreased  1  1/189 (0.53%)  0/193 (0.00%) 
Weight decreased  1  1/189 (0.53%)  0/193 (0.00%) 
Musculoskeletal and connective tissue disorders     
Axillary mass  1  1/189 (0.53%)  0/193 (0.00%) 
Product Issues     
Device damage  1  1/189 (0.53%)  0/193 (0.00%) 
Psychiatric disorders     
Intentional self-injury  1  1/189 (0.53%)  0/193 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis  1  1/189 (0.53%)  0/193 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Haemoptysis  1  3/189 (1.59%)  0/193 (0.00%) 
Pleural effusion  1  1/189 (0.53%)  0/193 (0.00%) 
Pneumothorax spontaneous  1  1/189 (0.53%)  0/193 (0.00%) 
Pulmonary embolism  1  1/189 (0.53%)  0/193 (0.00%) 
Skin and subcutaneous tissue disorders     
Rash pruritic  1  0/189 (0.00%)  1/193 (0.52%) 
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo VX-659/TEZ/IVA TC
Affected / at Risk (%) Affected / at Risk (%)
Total   166/189 (87.83%)   141/193 (73.06%) 
Gastrointestinal disorders     
Diarrhoea  1  16/189 (8.47%)  17/193 (8.81%) 
Nausea  1  24/189 (12.70%)  8/193 (4.15%) 
Abdominal pain upper  1  10/189 (5.29%)  3/193 (1.55%) 
Vomiting  1  11/189 (5.82%)  7/193 (3.63%) 
Constipation  1  5/189 (2.65%)  11/193 (5.70%) 
General disorders     
Pyrexia  1  15/189 (7.94%)  13/193 (6.74%) 
Fatigue  1  19/189 (10.05%)  9/193 (4.66%) 
Infections and infestations     
Infective pulmonary exacerbation of cystic fibrosis  1  79/189 (41.80%)  21/193 (10.88%) 
Upper respiratory tract infection  1  7/189 (3.70%)  35/193 (18.13%) 
Nasopharyngitis  1  16/189 (8.47%)  26/193 (13.47%) 
Investigations     
Alanine aminotransferase increased  1  2/189 (1.06%)  17/193 (8.81%) 
Blood creatine phosphokinase increased  1  7/189 (3.70%)  13/193 (6.74%) 
Aspartate aminotransferase increased  1  4/189 (2.12%)  16/193 (8.29%) 
Nervous system disorders     
Headache  1  31/189 (16.40%)  26/193 (13.47%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  68/189 (35.98%)  34/193 (17.62%) 
Oropharyngeal pain  1  13/189 (6.88%)  20/193 (10.36%) 
Sputum increased  1  38/189 (20.11%)  28/193 (14.51%) 
Haemoptysis  1  19/189 (10.05%)  6/193 (3.11%) 
Respiration abnormal  1  14/189 (7.41%)  7/193 (3.63%) 
Productive cough  1  14/189 (7.41%)  3/193 (1.55%) 
Nasal congestion  1  11/189 (5.82%)  11/193 (5.70%) 
Skin and subcutaneous tissue disorders     
Rash  1  10/189 (5.29%)  10/193 (5.18%) 
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Monitor
Organization: Vertex Pharmaceuticals Incorporated
Phone: 617-341-6777
EMail: medicalinfo@vrtx.com
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Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT03447249    
Other Study ID Numbers: VX17-659-102
2017-004132-11 ( EudraCT Number )
First Submitted: February 21, 2018
First Posted: February 27, 2018
Results First Submitted: February 5, 2020
Results First Posted: March 13, 2020
Last Update Posted: March 13, 2020