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A Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Subjects With Cystic Fibrosis Who Have an F508del-CFTR Mutation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02565914
Recruitment Status : Active, not recruiting
First Posted : October 1, 2015
Results First Posted : June 16, 2020
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: TEZ/IVA
Drug: IVA
Enrollment 1044
Recruitment Details This study consists of 3 parts: Part A, B and C. Part A has completed while Parts B and C are ongoing. Primary Completion was achieved based on Part A in May 2019. Only Part A results are reported. Complete results for Parts B and C will be updated within 1 year of study completion date.
Pre-assignment Details Participants from Parent Studies 103 (NCT02070744), 106 (NCT02347657), 107 (NCT02516410), 108 (NCT02392234), 109 (NCT02412111) and 111 (NCT02508207) were enrolled in this study. A total of 1044 participants were randomized in this study.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description All participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 103, 106, 107,108, 109 and 111 were to be administered TEZ 100 milligram (mg)/IVA 150 mg fixed-dose combination tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Period Title: Overall Study
Started 1044
Safety Set [1] 1042
Completed 951
Not Completed 93
Reason Not Completed
Adverse Event             17
Withdrawal of consent (not due to AE)             25
Lost to Follow-up             12
Death (not treatment emergent)             1
Other noncompliance             6
Physician Decision             6
Parent study termination by sponsor             1
Commercial drug available             5
Other             18
Enrolled, but did not receive study drug             2
[1]
Received at least 1 dose of TEZ/IVA
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description All participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 103, 106, 107,108, 109 and 111 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose combination tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Baseline Participants 1042
Hide Baseline Analysis Population Description
Safety Set was defined as all participants who received at least 1 dose of study drug in Part A regardless of their genotype.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1042 participants
29.2  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1042 participants
Female
503
  48.3%
Male
539
  51.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1042 participants
Hispanic or Latino
24
   2.3%
Not Hispanic or Latino
1001
  96.1%
Unknown or Not Reported
17
   1.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1042 participants
American Indian or Alaska Native
1
   0.1%
Asian
2
   0.2%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
7
   0.7%
White
1015
  97.4%
More than one race
0
   0.0%
Unknown or Not Reported
17
   1.6%
1.Primary Outcome
Title Part A: 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 Day 1 up to Week 100
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Set was defined as all participants who received at least 1 dose of study drug in Part A regardless of their genotype.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 103, 106, 107,108, 109 and 111 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose combination tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 1042
Measure Type: Number
Unit of Measure: participants
Participants with any AEs 995
Participants with SAEs 351
2.Secondary Outcome
Title Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 106/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or TEZ/IVA in parent study 106 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 459
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage points
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 231 participants
2.1
(0.8 to 3.3)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 228 participants
2.0
(0.7 to 3.2)
3.Secondary Outcome
Title Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 108/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or IVA monotherapy or TEZ/IVA in parent study 108 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 226
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage points
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 80 participants
4.1
(2.2 to 6.0)
IVA-TEZ/IVA: Change at Week 96 Number Analyzed 70 participants
6.7
(4.7 to 8.7)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 76 participants
7.5
(5.6 to 9.4)
4.Secondary Outcome
Title Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 103/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 103 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received TEZ/IVA in parent study 103 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: percentage points
2.7  (10.0)
5.Secondary Outcome
Title Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 111/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 111 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo and TEZ/IVA in parent study 111 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 33
Mean (Standard Deviation)
Unit of Measure: percentage points
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 7 participants
4.1  (10.2)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 26 participants
2.6  (6.6)
6.Secondary Outcome
Title Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 106/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or TEZ/IVA in parent study 106 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 459
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 231 participants
4.3
(2.1 to 6.5)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 228 participants
4.2
(2.0 to 6.4)
7.Secondary Outcome
Title Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 108/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or IVA monotherapy or TEZ/IVA in parent study 108 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 226
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percent change
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 80 participants
7.9
(4.7 to 11.1)
IVA-TEZ/IVA: Change at Week 96 Number Analyzed 70 participants
11.6
(8.2 to 15.0)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 76 participants
13.0
(9.7 to 16.2)
8.Secondary Outcome
Title Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 103/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 103 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received TEZ/IVA in parent study 103 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: percent change
6.4  (21.1)
9.Secondary Outcome
Title Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set
Hide Description FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 111/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 111 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo and TEZ/IVA in parent study 111 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 33
Mean (Standard Deviation)
Unit of Measure: percent change
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 7 participants
6.1  (14.4)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 26 participants
5.2  (11.5)
10.Secondary Outcome
Title Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set
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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time Frame From Baseline up to Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 106/110 PEx analysis set included study 106 participants who received TEZ/IVA in Study 106 or Study 110.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or TEZ/IVA in parent study 106 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in part A of this study.
Overall Number of Participants Analyzed 479
Measure Type: Number
Unit of Measure: PEx events
Placebo-TEZ/IVA Number Analyzed 231 participants
306
TEZ/IVA-TEZ/IVA Number Analyzed 248 participants
423
11.Secondary Outcome
Title Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set
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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline up to Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 108/110 PEx analysis set included study 108 participants who received TEZ/IVA in Study 108 or Study 110.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or IVA monotherapy or TEZ/IVA in parent study 108 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 233
Measure Type: Number
Unit of Measure: PEx events
Placebo-TEZ/IVA Number Analyzed 81 participants
89
IVA-TEZ/IVA Number Analyzed 74 participants
51
TEZ/IVA-TEZ/IVA Number Analyzed 78 participants
46
12.Secondary Outcome
Title Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set
Hide Description BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 106/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or TEZ/IVA in parent study 106 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 459
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kg/m^2
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 231 participants
0.47
(0.30 to 0.65)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 228 participants
0.38
(0.20 to 0.55)
13.Secondary Outcome
Title Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set
Hide Description BMI was defined as weight in kg divided by height in square meter (m^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 108/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or IVA monotherapy or TEZ/IVA in parent study 108 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 226
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kg/m^2
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 80 participants
1.07
(0.59 to 1.55)
IVA-TEZ/IVA: Change at Week 96 Number Analyzed 70 participants
0.96
(0.45 to 1.47)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 76 participants
1.05
(0.56 to 1.55)
14.Secondary Outcome
Title Part A: Absolute Change in Body Mass Index (BMI) for 103/110 Efficacy Set
Hide Description BMI was defined as weight in kg divided by height in square meter (m^2). Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 103/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 103 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received TEZ/IVA in parent study 103 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: kg/m^2
1.38  (1.73)
15.Secondary Outcome
Title Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set
Hide Description BMI was defined as weight in kg divided by height in square meter (m^2). Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 111/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 111 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo and TEZ/IVA in parent study 111 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 33
Mean (Standard Deviation)
Unit of Measure: kg/m^2
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 7 participants
1.59  (2.08)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 26 participants
0.26  (0.88)
16.Secondary Outcome
Title Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set
Hide Description The z-score is a statistical measure to describe whether a mean was above or below the standard. 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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 106/110 efficacy set included all enrolled participants <20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or TEZ/IVA in parent study 106 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose combination tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 93
Least Squares Mean (95% Confidence Interval)
Unit of Measure: z-score
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 44 participants
0.10
(-0.04 to 0.25)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 49 participants
-0.14
(-0.28 to 0.00)
17.Secondary Outcome
Title Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set
Hide Description The z-score is a statistical measure to describe whether a mean was above or below the standard. 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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 108/110 efficacy set included all enrolled participants <20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or IVA monotherapy or TEZ/IVA in parent study 108 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 30
Least Squares Mean (95% Confidence Interval)
Unit of Measure: z-score
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 13 participants
0.11
(-0.32 to 0.54)
IVA-TEZ/IVA: Change at Week 96 Number Analyzed 7 participants
0.07
(-0.52 to 0.65)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 10 participants
0.30
(-0.21 to 0.80)
18.Secondary Outcome
Title Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set
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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 106/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or TEZ/IVA in parent study 106 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 459
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 231 participants
1.7
(-0.6 to 4.0)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 228 participants
3.0
(0.7 to 5.3)
19.Secondary Outcome
Title Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set
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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 108/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or IVA monotherapy or TEZ/IVA in parent study 108 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 226
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 80 participants
10.3
(7.0 to 13.6)
IVA-TEZ/IVA: Change at Week 96 Number Analyzed 70 participants
11.2
(7.7 to 14.7)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 76 participants
13.8
(10.3 to 17.2)
20.Secondary Outcome
Title Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/110 Efficacy Set
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. Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 103/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 103 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received TEZ/IVA in parent study 103 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: units on a scale
8.6  (12.1)
21.Secondary Outcome
Title Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set
Hide Description Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 106/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or TEZ/IVA in parent study 106 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 459
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kg
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 231 participants
2.0
(1.4 to 2.5)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 228 participants
2.1
(1.5 to 2.6)
22.Secondary Outcome
Title Part A: Absolute Change in Body Weight for 108/110 Efficacy Set
Hide Description Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 108/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or IVA monotherapy or TEZ/IVA in parent study 108 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 226
Least Squares Mean (95% Confidence Interval)
Unit of Measure: kg
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 80 participants
3.5
(1.9 to 5.1)
IVA-TEZ/IVA: Change at Week 96 Number Analyzed 70 participants
3.5
(1.8 to 5.2)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 76 participants
3.6
(2.0 to 5.2)
23.Secondary Outcome
Title Part A: Absolute Change in Body Weight for 103/110 Efficacy Set
Hide Description Data are reported for TEZ/IVA-TEZ/IVA group (participants who received TEZ/IVA in both parent study 103 and in current study 110). Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 103/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 103 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received TEZ/IVA in parent study 103 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 23
Mean (Standard Deviation)
Unit of Measure: kg
4.0  (5.0)
24.Secondary Outcome
Title Part A: Absolute Change in Body Weight for 111/110 Efficacy Set
Hide Description Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 111 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 111 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 111/110 efficacy set included all enrolled participants who received at least 1 dose of study drug in Part A and rolled over from parent study 111 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo and TEZ/IVA in parent study 111 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 33
Mean (Standard Deviation)
Unit of Measure: kg
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 7 participants
4.2  (5.7)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 26 participants
0.6  (2.6)
25.Secondary Outcome
Title Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set
Hide Description The z-score is a statistical measure to describe whether a mean was above or below the standard. 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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 106/110 efficacy set included all enrolled participants <20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or TEZ/IVA in parent study 106 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 93
Least Squares Mean (95% Confidence Interval)
Unit of Measure: z-score
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 44 participants
0.07
(-0.06 to 0.20)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 49 participants
-0.06
(-0.19 to 0.07)
26.Secondary Outcome
Title Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set
Hide Description The z-score is a statistical measure to describe whether a mean was above or below the standard. 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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 108/110 efficacy set included all enrolled participants <20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or IVA monotherapy or TEZ/IVA in parent study 108 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 30
Least Squares Mean (95% Confidence Interval)
Unit of Measure: z-score
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 13 participants
0.15
(-0.25 to 0.55)
IVA-TEZ/IVA: Change at Week 96 Number Analyzed 7 participants
0.09
(-0.45 to 0.62)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 10 participants
0.43
(-0.04 to 0.90)
27.Secondary Outcome
Title Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set
Hide Description The z-score is a statistical measure to describe whether a mean was above or below the standard. 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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline except for Placebo-TEZ/IVA category, for which baseline was study 110 baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 106/110 efficacy set included all enrolled participants <20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 106 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or TEZ/IVA in parent study 106 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose combination tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 91
Least Squares Mean (95% Confidence Interval)
Unit of Measure: z-score
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 42 participants
0.01
(-0.08 to 0.11)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 49 participants
0.13
(0.04 to 0.22)
28.Secondary Outcome
Title Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set
Hide Description The z-score is a statistical measure to describe whether a mean was above or below the standard. 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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan. Baseline was defined as the parent study baseline.
Time Frame From Baseline at Study 110 Week 96
Hide Outcome Measure Data
Hide Analysis Population Description
The 108/110 efficacy set included all enrolled participants <20 years of age at Screening who received at least 1 dose of study drug in Part A and rolled over from parent study 108 and had pre-defined CFTR genotypes.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or IVA monotherapy or TEZ/IVA in parent study 108 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 30
Least Squares Mean (95% Confidence Interval)
Unit of Measure: z-score
Placebo-TEZ/IVA: Change at Week 96 Number Analyzed 13 participants
-0.04
(-0.23 to 0.15)
IVA-TEZ/IVA: Change at Week 96 Number Analyzed 7 participants
0.20
(-0.05 to 0.45)
TEZ/IVA-TEZ/IVA: Change at Week 96 Number Analyzed 10 participants
0.23
(0.00 to 0.46)
29.Secondary Outcome
Title Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set
Hide Description Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx 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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 106 and TEZ/IVA in current study 110) and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 106 and in current study 110) as per pre-specified analysis plan.
Time Frame 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The 106/110 PEx analysis set included study 106 participants who received TEZ/IVA in Study 106 or Study 110.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or TEZ/IVA in parent study 106 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose combination tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 479
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: event-free probability
Placebo-TEZ/IVA Number Analyzed 231 participants
0.470
(0.402 to 0.535)
TEZ/IVA-TEZ/IVA Number Analyzed 248 participants
0.438
(0.374 to 0.501)
30.Secondary Outcome
Title Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set
Hide Description Time-to-first pulmonary exacerbation was analyzed using Kaplan-Meier estimates and expressed in terms of event-free probability. PEx 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. Data are reported separately for Placebo-TEZ/IVA category (participants who received placebo in parent study 108 and TEZ/IVA in current study 110); IVA-TEZ/IVA category (participants who received IVA monotherapy in parent study 108 and TEZ/IVA in current study 110); and TEZ/IVA-TEZ/IVA category (participants who received TEZ/IVA in both parent study 108 and in current study 110) as per pre-specified analysis plan.
Time Frame 96 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The 108/110 PEx analysis set included study 108 participants who received TEZ/IVA in Study 108 or Study 110.
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description:
All participants who received Placebo or IVA monotherapy or TEZ/IVA in parent study 108 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose combination tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 233
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: event-free probability
Placebo-TEZ/IVA Number Analyzed 81 participants
0.497
(0.383 to 0.601)
IVA-TEZ/IVA Number Analyzed 74 participants
0.493
(0.372 to 0.603)
TEZ/IVA-TEZ/IVA Number Analyzed 78 participants
0.639
(0.519 to 0.737)
31.Secondary Outcome
Title Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA)
Hide Description [Not Specified]
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic set included data for all participants who received TEZ/IVA treatment and met PK data inclusion and exclusion criteria.
Arm/Group Title Part A: All Participants
Hide Arm/Group Description:
All participants who received TEZ/IVA or IVA monotherapy or Placebo in parent studies (103, 106, 107,108, 109 and 111) were to be administered TEZ 100 micrograms (mg)/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg in the evening for 96 weeks in Part A of this study.
Overall Number of Participants Analyzed 853
Mean (Standard Deviation)
Unit of Measure: nanogram/milliliter (ng/mL)
VX-661 2070  (1390)
M1-661 4580  (2080)
IVA 892  (700)
M1-IVA 1740  (1070)
Time Frame Day 1 up to Week 100
Adverse Event Reporting Description There were no Treatment-emergent deaths in the study. Two participants died after the treatment-emergent period.
 
Arm/Group Title Part A: TEZ/IVA
Hide Arm/Group Description All participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 103, 106, 107,108, 109 and 111 were to be administered TEZ 100 mg/IVA 150 mg fixed-dose combination tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks in Part A of this study.
All-Cause Mortality
Part A: TEZ/IVA
Affected / at Risk (%)
Total   2/1042 (0.19%) 
Hide Serious Adverse Events
Part A: TEZ/IVA
Affected / at Risk (%)
Total   351/1042 (33.69%) 
Blood and lymphatic system disorders   
Anaemia  1  1/1042 (0.10%) 
Bone marrow failure  1  1/1042 (0.10%) 
Lymphadenitis  1  1/1042 (0.10%) 
Cardiac disorders   
Cardiac failure  1  1/1042 (0.10%) 
Left ventricular dysfunction  1  1/1042 (0.10%) 
Myocarditis  1  1/1042 (0.10%) 
Ear and labyrinth disorders   
Vertigo  1  1/1042 (0.10%) 
Endocrine disorders   
Pituitary enlargement  1  1/1042 (0.10%) 
Gastrointestinal disorders   
Abdominal pain  1  7/1042 (0.67%) 
Colitis  1  1/1042 (0.10%) 
Constipation  1  8/1042 (0.77%) 
Cyclic vomiting syndrome  1  1/1042 (0.10%) 
Distal intestinal obstruction syndrome  1  12/1042 (1.15%) 
Enteritis  1  1/1042 (0.10%) 
Gastritis  1  1/1042 (0.10%) 
Gastrooesophageal reflux disease  1  1/1042 (0.10%) 
Ileus  1  1/1042 (0.10%) 
Intestinal obstruction  1  4/1042 (0.38%) 
Large intestinal obstruction  1  1/1042 (0.10%) 
Melaena  1  1/1042 (0.10%) 
Nausea  1  2/1042 (0.19%) 
Oesophageal achalasia  1  1/1042 (0.10%) 
Pancreatitis acute  1  2/1042 (0.19%) 
Pancreatitis chronic  1  1/1042 (0.10%) 
Small intestinal obstruction  1  2/1042 (0.19%) 
Volvulus  1  1/1042 (0.10%) 
Vomiting  1  2/1042 (0.19%) 
General disorders   
Fatigue  1  1/1042 (0.10%) 
General physical health deterioration  1  1/1042 (0.10%) 
Medical device site erythema  1  1/1042 (0.10%) 
Non-cardiac chest pain  1  1/1042 (0.10%) 
Pyrexia  1  1/1042 (0.10%) 
Hepatobiliary disorders   
Cholecystitis  1  1/1042 (0.10%) 
Cholecystitis acute  1  1/1042 (0.10%) 
Cholecystitis chronic  1  2/1042 (0.19%) 
Cholelithiasis  1  1/1042 (0.10%) 
Gallbladder rupture  1  1/1042 (0.10%) 
Hepatic mass  1  1/1042 (0.10%) 
Hepatitis toxic  1  1/1042 (0.10%) 
Hypertransaminasaemia  1  1/1042 (0.10%) 
Immune system disorders   
Anaphylactic reaction  1  2/1042 (0.19%) 
Drug hypersensitivity  1  2/1042 (0.19%) 
Food allergy  1  1/1042 (0.10%) 
Infections and infestations   
Anal abscess  1  2/1042 (0.19%) 
Appendicitis  1  5/1042 (0.48%) 
Bronchopulmonary aspergillosis allergic  1  1/1042 (0.10%) 
Clostridium difficile infection  1  1/1042 (0.10%) 
Diverticulitis  1  1/1042 (0.10%) 
Erysipelas  1  1/1042 (0.10%) 
Groin abscess  1  1/1042 (0.10%) 
Infective exacerbation of bronchiectasis  1  4/1042 (0.38%) 
Infective pulmonary exacerbation of cystic fibrosis  1  243/1042 (23.32%) 
Influenza  1  7/1042 (0.67%) 
Lower respiratory tract infection  1  2/1042 (0.19%) 
Lung infection  1  2/1042 (0.19%) 
Lung infection pseudomonal  1  1/1042 (0.10%) 
Pneumonia  1  7/1042 (0.67%) 
Pneumonia pseudomonal  1  1/1042 (0.10%) 
Respiratory syncytial virus infection  1  1/1042 (0.10%) 
Respiratory tract infection  1  1/1042 (0.10%) 
Respiratory tract infection viral  1  3/1042 (0.29%) 
Salpingitis  1  1/1042 (0.10%) 
Sinusitis  1  2/1042 (0.19%) 
Tonsillitis  1  2/1042 (0.19%) 
Vascular device infection  1  2/1042 (0.19%) 
Injury, poisoning and procedural complications   
Anaesthetic complication cardiac  1  1/1042 (0.10%) 
Foot fracture  1  1/1042 (0.10%) 
Ligament rupture  1  1/1042 (0.10%) 
Meniscus injury  1  2/1042 (0.19%) 
Patella fracture  1  1/1042 (0.10%) 
Peroneal nerve injury  1  1/1042 (0.10%) 
Post lumbar puncture syndrome  1  1/1042 (0.10%) 
Post procedural haemorrhage  1  1/1042 (0.10%) 
Procedural pain  1  1/1042 (0.10%) 
Radius fracture  1  1/1042 (0.10%) 
Investigations   
Alanine aminotransferase increased  1  3/1042 (0.29%) 
Aspartate aminotransferase increased  1  4/1042 (0.38%) 
Bacterial test positive  1  1/1042 (0.10%) 
Blood creatine phosphokinase increased  1  7/1042 (0.67%) 
Blood creatinine increased  1  1/1042 (0.10%) 
Forced expiratory volume decreased  1  3/1042 (0.29%) 
Influenza A virus test positive  1  1/1042 (0.10%) 
Influenza B virus test positive  1  1/1042 (0.10%) 
Pulmonary function test decreased  1  1/1042 (0.10%) 
Respiratory syncytial virus test positive  1  1/1042 (0.10%) 
Urine amphetamine positive  1  1/1042 (0.10%) 
Weight decreased  1  1/1042 (0.10%) 
Metabolism and nutrition disorders   
Dehydration  1  2/1042 (0.19%) 
Hyperglycaemia  1  1/1042 (0.10%) 
Hypoglycaemia  1  1/1042 (0.10%) 
Hypokalaemia  1  1/1042 (0.10%) 
Hypomagnesaemia  1  1/1042 (0.10%) 
Hypovolaemia  1  1/1042 (0.10%) 
Malnutrition  1  1/1042 (0.10%) 
Musculoskeletal and connective tissue disorders   
Intervertebral disc protrusion  1  1/1042 (0.10%) 
Musculoskeletal chest pain  1  1/1042 (0.10%) 
Neuropathic arthropathy  1  1/1042 (0.10%) 
Rhabdomyolysis  1  1/1042 (0.10%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Adenocarcinoma of colon  1  1/1042 (0.10%) 
Basal cell carcinoma  1  1/1042 (0.10%) 
Benign male reproductive tract neoplasm  1  1/1042 (0.10%) 
Malignant glioma  1  1/1042 (0.10%) 
Oesophageal adenocarcinoma  1  1/1042 (0.10%) 
Oesophageal carcinoma  1  1/1042 (0.10%) 
Schwannoma  1  1/1042 (0.10%) 
Nervous system disorders   
Dizziness  1  1/1042 (0.10%) 
Facial paralysis  1  1/1042 (0.10%) 
Headache  1  2/1042 (0.19%) 
Loss of consciousness  1  1/1042 (0.10%) 
Migraine  1  2/1042 (0.19%) 
Neuropathy peripheral  1  1/1042 (0.10%) 
Quadrantanopia  1  1/1042 (0.10%) 
Seizure  1  1/1042 (0.10%) 
Syncope  1  1/1042 (0.10%) 
Toxic encephalopathy  1  1/1042 (0.10%) 
Psychiatric disorders   
Anxiety  1  5/1042 (0.48%) 
Bipolar I disorder  1  1/1042 (0.10%) 
Depression  1  2/1042 (0.19%) 
Disruptive mood dysregulation disorder  1  1/1042 (0.10%) 
Panic attack  1  1/1042 (0.10%) 
Paranoia  1  1/1042 (0.10%) 
Suicidal ideation  1  1/1042 (0.10%) 
Suicide attempt  1  3/1042 (0.29%) 
Renal and urinary disorders   
Acute kidney injury  1  1/1042 (0.10%) 
Hydronephrosis  1  1/1042 (0.10%) 
Nephrolithiasis  1  4/1042 (0.38%) 
Renal colic  1  1/1042 (0.10%) 
Renal failure  1  1/1042 (0.10%) 
Ureterolithiasis  1  2/1042 (0.19%) 
Reproductive system and breast disorders   
Gynaecomastia  1  1/1042 (0.10%) 
Ovarian cyst  1  1/1042 (0.10%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  1/1042 (0.10%) 
Haemoptysis  1  25/1042 (2.40%) 
Nasal polyps  1  1/1042 (0.10%) 
Pleural effusion  1  1/1042 (0.10%) 
Pleuritic pain  1  1/1042 (0.10%) 
Pneumothorax spontaneous  1  2/1042 (0.19%) 
Pulmonary embolism  1  1/1042 (0.10%) 
Sinus polyp  1  1/1042 (0.10%) 
Sleep apnoea syndrome  1  1/1042 (0.10%) 
Sputum increased  1  1/1042 (0.10%) 
Skin and subcutaneous tissue disorders   
Rash  1  1/1042 (0.10%) 
Urticarial vasculitis  1  1/1042 (0.10%) 
Vascular disorders   
Deep vein thrombosis  1  1/1042 (0.10%) 
1
Term from vocabulary, Meddra 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Part A: TEZ/IVA
Affected / at Risk (%)
Total   935/1042 (89.73%) 
Gastrointestinal disorders   
Abdominal pain  1  101/1042 (9.69%) 
Constipation  1  69/1042 (6.62%) 
Diarrhoea  1  105/1042 (10.08%) 
Nausea  1  105/1042 (10.08%) 
Vomiting  1  80/1042 (7.68%) 
General disorders   
Fatigue  1  100/1042 (9.60%) 
Pyrexia  1  135/1042 (12.96%) 
Infections and infestations   
Infective pulmonary exacerbation of cystic fibrosis  1  444/1042 (42.61%) 
Influenza  1  62/1042 (5.95%) 
Nasopharyngitis  1  227/1042 (21.79%) 
Rhinitis  1  55/1042 (5.28%) 
Sinusitis  1  80/1042 (7.68%) 
Upper respiratory tract infection  1  135/1042 (12.96%) 
Viral upper respiratory tract infection  1  69/1042 (6.62%) 
Investigations   
Aspartate aminotransferase increased  1  53/1042 (5.09%) 
Blood creatine phosphokinase increased  1  76/1042 (7.29%) 
Pulmonary function test decreased  1  55/1042 (5.28%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  62/1042 (5.95%) 
Back pain  1  57/1042 (5.47%) 
Nervous system disorders   
Headache  1  146/1042 (14.01%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  374/1042 (35.89%) 
Dyspnoea  1  99/1042 (9.50%) 
Haemoptysis  1  167/1042 (16.03%) 
Nasal congestion  1  77/1042 (7.39%) 
Oropharyngeal pain  1  136/1042 (13.05%) 
Productive cough  1  56/1042 (5.37%) 
Rhinorrhoea  1  55/1042 (5.28%) 
Sinus congestion  1  53/1042 (5.09%) 
Sputum increased  1  223/1042 (21.40%) 
1
Term from vocabulary, MedDRA 22.0
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
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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: NCT02565914    
Other Study ID Numbers: VX14-661-110
2014-004827-29 ( EudraCT Number )
First Submitted: September 18, 2015
First Posted: October 1, 2015
Results First Submitted: May 28, 2020
Results First Posted: June 16, 2020
Last Update Posted: June 16, 2020