A Study Evaluating the Long Term Safety and Efficacy of VX-659 Combination Therapy

• Sponsor: Vertex Pharmaceuticals Incorporated (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03447262
• Collaborator: (none)
• Enrollment: 484
• Locations: 100
• Arm: 1
• Actual Duration (Months): 25.9
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate the long-term safety and tolerability of VX-659 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous or heterozygous for the F508del mutation.

Condition or Disease	Intervention/Treatment	Phase
Cystic Fibrosis	Drug: VX-659/TEZ/IVA; Drug: IVA	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 484 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Open-label Study Evaluating the Long Term Safety and Efficacy of VX-659 Combination Therapy in Subjects With Cystic Fibrosis Who Are Homozygous or Heterozygous for the F508del Mutation
• Actual Study Start Date: Jul 13, 2018
• Actual Primary Completion Date: Sep 9, 2020
• Actual Study Completion Date: Sep 9, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VX-659/TEZ/IVA TC Participants from parent studies VX17-659-102 (NCT03447249) or VX17-659-103 (NCT03460990) were administered VX-659 240 milligrams (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the TC treatment period for up to 96 weeks in the current study VX17-659-105.	Drug: VX-659/TEZ/IVA; Fixed-dose combination tablets for oral administration qd in the morning.; Other Names: VX-659/VX-661/VX-770 VX-659/tezacaftor/ivacaftor ; Drug: IVA; IVA tablet qd in the evening.; Other Names: VX-770 ivacaftor

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [From Day 1 up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First in the Current Study 659-105 (up to Week 100)]

Secondary Outcome Measures

1. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102 [From Baseline at Week 72 (Study 659-105)]

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

2. Absolute Change in ppFEV1 for Participants From the Parent Study 659-103 [From Baseline at Week 72 (Study 659-105)]

   FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

3. Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102 [From Baseline at Week 24 (Study 659-105)]

   Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

4. Absolute Change in SwCl for Participants From the Parent Study 659-103 [From Baseline at Week 24 (Study 659-105)]

   Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

5. Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102 [From Baseline up to Week 96 (Study 659-105)]

   PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.

6. Number of PEx for Participants From the Parent Study 659-103 [From Baseline up to Week 96 (Study 659-105)]

   PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported for overall participants from the parent study 659-103, that is combined for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.

7. Number of Participants With at Least One PEx for Participants From the Parent Study 659-102 [From Baseline up to Week 96 (Study 659-105)]

   PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the Kaplan-Meier (KM) method. However, because way less than 50% of participants had events, median time-to-first event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported separately for those in Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105). Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.

8. Number of Participants With at Least One PEx for Participants From the Parent Study 659-103 [From Baseline up to Week 96 (Study 659-105)]

   PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the KM method. However, because way less than 50% of participants had events, median time-to-first-event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported for all participants from the parent study 659-103, that is combined for those in the TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105). Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.

9. Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102 [From Baseline at Week 72 (Study 659-105)]

   BMI was defined as weight in kilograms (kg) divided by squared height in meters (m^2). The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

10. Absolute Change in BMI for Participants From the Parent Study 659-103 [From Baseline at Week 72 (Study 659-105)]

    BMI was defined as weight in kg divided by squared height in meters (m^2). The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

11. Absolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline) [From Baseline at Week 60 (Study 659-105)]

    BMI was defined as weight in kg divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

12. Absolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline) [From Baseline at Week 60 (Study 659-105)]

    BMI was defined as weight in kg divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

13. Absolute Change in Body Weight for Participants From the Parent Study 659-102 [From Baseline at Week 72 (Study 659-105)]

    The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

14. Absolute Change in Body Weight for Participants From the Parent Study 659-103 [From Baseline at Week 72 (Study 659-105)]

    The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

15. Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102 [From Baseline at Week 72 (Study 659-105)]

    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. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

16. Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103 [From Baseline at Week 72 (Study 659-105)]

    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. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Completed study drug treatment in a parent study; or had study drug interruption(s) in a parent study but completed study visits up to the last scheduled visit of the Treatment Period in the parent study.

Exclusion Criteria:

• History of drug intolerance in a parent study that would pose an additional risk to the subject in the opinion of the investigator.

• Current participation in an investigational drug trial (other than a parent study)

Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Stanford University	Palo Alto	California	United States	94304
3	Children's Hospital Colorado	Aurora	Colorado	United States	80045
4	Hartford Hospital	Hartford	Connecticut	United States	06102
5	Yale New Haven Medical Center	New Haven	Connecticut	United States	06511
6	University of Miami Miller School of Medicine	Miami	Florida	United States	33136
7	Nicklaus Children's Hospital	Miami	Florida	United States	33155
8	Orlando Health, Inc.- Arnold Palmer Hospital for Children (APH)	Orlando	Florida	United States	32806
9	Johns Hopkins All Children's Hospital Outpatient Care Center	Saint Petersburg	Florida	United States	33701
10	St. Luke's CF Center of Idaho	Boise	Idaho	United States	83712
11	Cystic Fibrosis Center of Chicago	Glenview	Illinois	United States	60025
12	Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants	Niles	Illinois	United States	60714
13	Indiana Clinical Research Center, IU Health University Hospital	Indianapolis	Indiana	United States	46202
14	The University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
15	University of Kentucky	Lexington	Kentucky	United States	40536
16	Kosair Charities Pediatric Clinical Research Unit	Louisville	Kentucky	United States	40202
17	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287
18	Boston Children's Hospital	Boston	Massachusetts	United States	02115
19	UMass Memorial Medical Center	Worcester	Massachusetts	United States	01655
20	Michigan Medicine	Ann Arbor	Michigan	United States	48109-5212
21	Spectrum Health Medical Group Adult Cystic Fibrosis Care Center	Grand Rapids	Michigan	United States	49546
22	University of Minnesota	Minneapolis	Minnesota	United States	55455
23	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
24	The Children's Mercy Hospital	Kansas City	Missouri	United States	64108
25	Washington University School of Medicine/ St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
26	Dartmouth Hitchcock, Manchester	Manchester	New Hampshire	United States	03104
27	Rutgers-Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08901
28	Albany Medical College	Albany	New York	United States	12208
29	CF Therapeutics Development Center of Western New York	Buffalo	New York	United States	14203
30	Northwell Health, Long Island Jewish Medical Center	New Hyde Park	New York	United States	11040
31	Columbia University Medical Center	New York	New York	United States	10032
32	SUNY Upstate Medical University	Syracuse	New York	United States	13210
33	Clinical Research of Charlotte	Charlotte	North Carolina	United States	28277
34	Duke University Medical Center	Durham	North Carolina	United States	27710
35	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
36	Santiago Reyes, M.D.	Oklahoma City	Oklahoma	United States	73112
37	Oregon Health & Science University	Portland	Oregon	United States	97239
38	Drexel University College of Medicine / Drexel Adult Cystic Fibrosis Center	Philadelphia	Pennsylvania	United States	19107
39	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
40	Sanford Children's Specialty Clinic	Sioux Falls	South Dakota	United States	57105
41	University of Tennessee Medical Center- Adult Cystic Fibrosis Clinic	Knoxville	Tennessee	United States	37920
42	Children's Foundation Research Center / Le Bonheur Children's Hospital	Memphis	Tennessee	United States	38103
43	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
44	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
45	Texas Children's Hospital	Houston	Texas	United States	77030
46	University of Utah/ Primary Children's Medical Center	Salt Lake City	Utah	United States	84132
47	Seattle Children's Hospital	Seattle	Washington	United States	98105
48	Providence Pediatric Pulmonary & Cystic Fibrosis Clinic	Spokane	Washington	United States	99204
49	Royal Adelaide Hospital	Adelaide		Australia
50	The Prince Charles Hospital	Chermside		Australia
51	Alfred Hospital	Melbourne		Australia
52	Institute for Respiratory Health, Sir Charles Gairdner Hospital	Nedlands		Australia
53	John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital	New Lambton		Australia
54	Telethon Kids Institute	Perth		Australia
55	Sydney Children's Hospital	Randwick		Australia
56	Lady Cilento Children's Hospital	South Brisbane		Australia
57	Stollery Children's Hospital	Edmonton		Canada
58	Queen Elizabeth II Health Sciences Center	Halifax		Canada
59	St. Michael's Hospital	Toronto		Canada
60	Juliane Marie Center, Rigshospitalet	Copenhagen		Denmark
61	Charite Paediatric Pulmonology Department	Berlin		Germany
62	Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen	Essen		Germany
63	Clinic of J.W. Goethe University	Frankfurt		Germany
64	Medizinische Hochschule Hannover	Hannover		Germany
65	Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin	Jena		Germany
66	Universitaetsklinkum Koeln, CF-Studienzentrum	Koeln		Germany
67	Universitatsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin	Lubeck		Germany
68	Pneumologische Praxis Pasing	Muenchen		Germany
69	Klinikum Innenstadt, University of Munich	München		Germany
70	Cork University Hospital	Cork		Ireland
71	Beaumont Hospital	Dublin		Ireland
72	Our Lady's Children's Hospital	Dublin		Ireland
73	St. Vincent's University Hospital	Dublin		Ireland
74	Temple Street Children's University Hospital	Dublin		Ireland
75	University Hospital Galway	Galway		Ireland
76	University Hospital Limerick	Limerick		Ireland
77	Lady Davis Carmel Medical Center	Haifa		Israel
78	Rambam Health Care Campus, Liver Unit	Haifa		Israel
79	Pediatrics Hadassah Medical Center	Jerusalem		Israel
80	Schneider Children's Medical Center	Petah Tikva		Israel
81	Sheba Medical Center	Tel HaShomer		Israel
82	Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY	Łomianki		Poland
83	Hospital Universitari Vall d Hebron	Barcelona		Spain
84	Hospital Universitari Vall d´Hebron Servicio de Broncoscopia	Barcelona		Spain
85	Hospital Universitario 12 de Octubre	Madrid		Spain
86	Hospital Universitario Infantil La Paz	Madrid		Spain
87	Parc Tauli Sabadell Hospital Universitari	Sabadell		Spain
88	Hospital Universitario Virgen del Rocio	Sevilla		Spain
89	Hospital Universitario y Politecnico La Fe	Valencia		Spain
90	Lindenhofspital - Quartier Bleu	Bern		Switzerland
91	Kinderspital Zuerich	Zürich		Switzerland
92	Papworth Hospital NHS Foundation Trust, Papworth Everard	Cambridge		United Kingdom
93	Clinical Research Facility, Queen Elizabeth University Hospital	Glasgow		United Kingdom
94	St. James University Hospital	Leeds		United Kingdom
95	Liverpool Head and Chest Hospital	Liverpool		United Kingdom
96	Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital	London		United Kingdom
97	Wythenshaw e Hospital	Manchester		United Kingdom
98	The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary	Newcastle Upon Tyne		United Kingdom
99	Wolfson Cystic Fibrosis Unit, City Campus	Nottingham		United Kingdom
100	All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough	Penarth		United Kingdom

Sponsors and Collaborators

• Vertex Pharmaceuticals Incorporated

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Oct 23, 2018
• Statistical Analysis Plan - Feb 4, 2020

More Information

Publications

None provided.

• Responsible Party: Vertex Pharmaceuticals Incorporated
• ClinicalTrials.gov Identifier: NCT03447262
• Other Study ID Numbers: VX17-659-105; 2017-004134-29
• First Posted: Feb 27, 2018
• Last Update Posted: Jan 25, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cystic Fibrosis; Fibrosis; Ivacaftor; VX-659

Study Results

Participant Flow

Recruitment Details	A total of 484 participants were enrolled from the parent studies VX17-659-102 (Study 659-102; NCT03447249) and VX17-659-103 (Study 659-103; NCT03460990). Out of which, 3 participants were enrolled but never dosed in the current study VX17-659-105 (Study 659-105). Therefore, the below results are presented for 481 participants.
Pre-assignment Detail	This study was conducted in cystic fibrosis (CF) participants aged 12 years or older who participated in parent studies 659-102 or 659-103. Eligible participants from the parent studies were enrolled in the current study 659-105.

Arm/Group Title	VX-659/TEZ/IVA Triple Combination (TC)
Arm/Group Description	Participants from the parent studies 659-102 or 659-103 were administered VX-659 240 milligrams (mg) once daily (qd)/TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) in the TC treatment period for up to 96 weeks in the current study 659-105.
Period Title: Overall Study
STARTED	481
COMPLETED	2
NOT COMPLETED	479

Baseline Characteristics

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants from parent studies 659-102 or 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Overall Participants	481
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.9 (9.7)
Sex: Female, Male (Count of Participants)
Female	219 45.5%
Male	262 54.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	14 2.9%
Not Hispanic or Latino	462 96%
Unknown or Not Reported	5 1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 0.6%
White	474 98.5%
More than one race	4 0.8%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame	From Day 1 up to 28 Days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First in the Current Study 659-105 (up to Week 100)

Outcome Measure Data

Analysis Population Description

Open label safety set (OL-SS) included all participants who received at least 1 dose of study drug in the current study 659-105.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants from parent studies 659-102 or 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	481
Participants With AEs	470 97.7%
Participants With SAEs	99 20.6%

2. Secondary Outcome

Title	Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 72 (Study 659-105)

Outcome Measure Data

Analysis Population Description

Open label full analysis set (OL-FAS) included all rolled over participants from the parent study 659-102 who received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received placebo (matched to VX-659/TEZ/IVA) or VX-659/TEZ/IVA in the parent study 659-102 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	371
Placebo - VX-659/TEZ/IVA	14.2 (7.8)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	10.3 (9.3)

3. Secondary Outcome

Title	Absolute Change in ppFEV1 for Participants From the Parent Study 659-103
Description	FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 72 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-103 who received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received TEZ/IVA or VX-659/TEZ/IVA in the parent study 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	110
TEZ/IVA - VX-659/TEZ/IVA	15.1 (11.9)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	11.5 (9.8)

4. Secondary Outcome

Title	Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102
Description	Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 24 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-102 who received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received placebo (matched to VX-659/TEZ/IVA) or VX-659/TEZ/IVA in the parent study 659-102 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	371
Placebo - VX-659/TEZ/IVA	-48.9 (20.4)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	-49.7 (20.1)

5. Secondary Outcome

Title	Absolute Change in SwCl for Participants From the Parent Study 659-103
Description	Sweat samples were collected using an approved collection device. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 24 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-103 who received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received TEZ/IVA or VX-659/TEZ/IVA in the parent study 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	110
TEZ/IVA - VX-659/TEZ/IVA	-45.7 (16.8)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	-53.5 (16.2)

6. Secondary Outcome

Title	Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102
Description	PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Time Frame	From Baseline up to Week 96 (Study 659-105)

Outcome Measure Data

Analysis Population Description

The cumulative TC efficacy set for PEx analysis included all participants who were randomized to VX-659/TEZ/IVA arm and received at least one dose of study drug during the parent study 659-102 and/or received at least one dose of study drug during the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received placebo (matched to VX-659/TEZ/IVA) or VX-659/TEZ/IVA in the parent study 659-102 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	375
Placebo - VX-659/TEZ/IVA	60
VX-659/TEZ/IVA - VX-659/TEZ/IVA	84

7. Secondary Outcome

Title	Number of PEx for Participants From the Parent Study 659-103
Description	PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The analysis was planned to be reported for overall participants from the parent study 659-103, that is combined for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Time Frame	From Baseline up to Week 96 (Study 659-105)

Outcome Measure Data

Analysis Population Description

The cumulative TC efficacy set for PEx analysis included all participants who were randomized to VX-659/TEZ/IVA arm and received at least one dose of study drug during the parent study 659-103 and/or received at least one dose of study drug during the current study 659-105.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received TEZ/IVA or VX-659/TEZ/IVA in the parent study 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	110
Number [PEx events]	39

8. Secondary Outcome

Title	Number of Participants With at Least One PEx for Participants From the Parent Study 659-102
Description	PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the Kaplan-Meier (KM) method. However, because way less than 50% of participants had events, median time-to-first event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported separately for those in Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-102 or/and VX-659/TEZ/IVA in the current study 659-105). Baseline was defined as the parent study baseline except for Placebo - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Time Frame	From Baseline up to Week 96 (Study 659-105)

Outcome Measure Data

Analysis Population Description

The cumulative TC efficacy set for PEx analysis included all participants who were randomized to VX-659/TEZ/IVA arm and received at least one dose of study drug during the parent study 659-102 and/or received at least one dose of study drug during the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received placebo (matched to VX-659/TEZ/IVA), TEZ/IVA or VX-659/TEZ/IVA in the parent studies 659-102 or 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	375
Placebo - VX-659/TEZ/IVA	43 8.9%
VX-659/TEZ/IVA - VX-659/TEZ/IVA	52 10.8%

9. Secondary Outcome

Title	Number of Participants With at Least One PEx for Participants From the Parent Study 659-103
Description	PEx was defined as treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for at least 4 sinopulmonary signs/symptoms. The time-to-first-PEx data were planned to be estimated using the KM method. However, because way less than 50% of participants had events, median time-to-first-event data were not estimable. Instead, the number of participants with at least one PEx event was assessed and reported for all participants from the parent study 659-103, that is combined for those in the TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and the VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in the parent study 659-103 or/and in the current study 659-105). Baseline was defined as the parent study baseline except for TEZ/IVA - VX-659/TEZ/IVA category, for which the baseline was defined as study 659-105 baseline.
Time Frame	From Baseline up to Week 96 (Study 659-105)

Outcome Measure Data

Analysis Population Description

The cumulative TC efficacy set for PEx analysis included all participants who were randomized to VX-659/TEZ/IVA arm and received at least one dose of study drug during the parent study 659-103 and/or received at least one dose of study drug during the current study 659-105.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received TEZ/IVA or VX-659/TEZ/IVA in the parent study 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	110
Number [participants]	28 5.8%

10. Secondary Outcome

Title	Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102
Description	BMI was defined as weight in kilograms (kg) divided by squared height in meters (m^2). The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 72 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-102 who received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received placebo (matched to VX-659/TEZ/IVA) or VX-659/TEZ/IVA in the parent study 659-102 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	371
Placebo - VX-659/TEZ/IVA	1.55 (1.35)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	1.43 (1.94)

11. Secondary Outcome

Title	Absolute Change in BMI for Participants From the Parent Study 659-103
Description	BMI was defined as weight in kg divided by squared height in meters (m^2). The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 72 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-103 who received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received TEZ/IVA or VX-659/TEZ/IVA in the parent study 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	110
TEZ/IVA - VX-659/TEZ/IVA	1.16 (1.68)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	0.90 (1.52)

12. Secondary Outcome

Title	Absolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline)
Description	BMI was defined as weight in kg divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 60 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-102 who were <=20 years old at parent study baseline and received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received placebo (matched to VX-659/TEZ/IVA) or VX-659/TEZ/IVA in the parent study 659-102 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	114
Placebo - VX-659/TEZ/IVA	0.22 (0.59)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	0.10 (0.44)

13. Secondary Outcome

Title	Absolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline)
Description	BMI was defined as weight in kg divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 60 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-103 who were <=20 years old at parent study baseline and received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received TEZ/IVA or VX-659/TEZ/IVA in the parent study 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	30
TEZ/IVA - VX-659/TEZ/IVA	NA (NA)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	NA (NA)

14. Secondary Outcome

Title	Absolute Change in Body Weight for Participants From the Parent Study 659-102
Description	The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 72 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-102 who received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received placebo (matched to VX-659/TEZ/IVA) or VX-659/TEZ/IVA in the parent study 659-102 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	371
Placebo - VX-659/TEZ/IVA	4.8 (4.4)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	4.3 (5.6)

15. Secondary Outcome

Title	Absolute Change in Body Weight for Participants From the Parent Study 659-103
Description	The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 72 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-103 who received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received TEZ/IVA or VX-659/TEZ/IVA in the parent study 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	110
TEZ/IVA - VX-659/TEZ/IVA	3.7 (4.9)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	3.2 (5.0)

16. Secondary Outcome

Title	Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102
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. The analysis was planned to be reported separately for Placebo - VX-659/TEZ/IVA category (participants who received placebo in the parent study 659-102 and VX-659/TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-102 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 72 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-102 who received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received placebo (matched to VX-659/TEZ/IVA) or VX-659/TEZ/IVA in the parent study 659-102 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	371
Placebo - VX-659/TEZ/IVA	16.7 (18.7)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	19.7 (17.4)

17. Secondary Outcome

Title	Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103
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. The analysis was planned to be reported separately for TEZ/IVA - VX-659/TEZ/IVA category (participants who received TEZ/IVA in the parent study 659-103 and VX-659-TEZ/IVA in the current study 659-105) and VX-659/TEZ/IVA - VX-659/TEZ/IVA category (participants who received VX-659/TEZ/IVA in both the parent study 659-103 and in the current study 659-105) as pre-specified in analysis plan. Baseline was defined as the parent study baseline.
Time Frame	From Baseline at Week 72 (Study 659-105)

Outcome Measure Data

Analysis Population Description

OL-FAS included all rolled over participants from the parent study 659-103 who received at least 1 dose of study drug in the current study 659-105. Here, "number analyzed" signifies participants who were evaluable for the specified category.

Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants who either received TEZ/IVA or VX-659/TEZ/IVA in the parent study 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
Measure Participants	110
TEZ/IVA - VX-659/TEZ/IVA	17.1 (18.2)
VX-659/TEZ/IVA - VX-659/TEZ/IVA	16.9 (17.3)

Adverse Events

Time Frame	From Day 1 up to 28 days After Last Dose of Study Drug or to the Completion of Study Participation Date, Whichever Occurs First in the Current Study 659-105 (up to Week 100)
Arm/Group Title	VX-659/TEZ/IVA TC
Arm/Group Description	Participants from parent studies 659-102 or 659-103 were administered VX-659 240 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the TC treatment period for up to 96 weeks in the current study 659-105.
All Cause Mortality
	VX-659/TEZ/IVA TC
	Affected / at Risk (%)	# Events
Total	2/481 (0.4%)
Serious Adverse Events
	VX-659/TEZ/IVA TC
	Affected / at Risk (%)	# Events
Total	99/481 (20.6%)
Cardiac disorders
Cardiac failure acute	1/481 (0.2%)
Restrictive cardiomyopathy	1/481 (0.2%)
Congenital, familial and genetic disorders
Cystic fibrosis related diabetes	1/481 (0.2%)
Ear and labyrinth disorders
Vertigo	1/481 (0.2%)
Gastrointestinal disorders
Abdominal pain	3/481 (0.6%)
Abdominal pain upper	1/481 (0.2%)
Constipation	2/481 (0.4%)
Distal intestinal obstruction syndrome	6/481 (1.2%)
Duodenitis	1/481 (0.2%)
Gastritis	1/481 (0.2%)
Gastrointestinal haemorrhage	1/481 (0.2%)
Intestinal obstruction	1/481 (0.2%)
Mechanical ileus	1/481 (0.2%)
Vomiting	1/481 (0.2%)
General disorders
Generalised oedema	1/481 (0.2%)
Systemic inflammatory response syndrome	1/481 (0.2%)
Hepatobiliary disorders
Autoimmune hepatitis	1/481 (0.2%)
Bile duct stone	1/481 (0.2%)
Biliary colic	1/481 (0.2%)
Cholangitis	1/481 (0.2%)
Cholecystitis	2/481 (0.4%)
Cholecystitis chronic	1/481 (0.2%)
Cholelithiasis	1/481 (0.2%)
Immune system disorders
Anaphylactic reaction	1/481 (0.2%)
Infections and infestations
Bacterial disease carrier	1/481 (0.2%)
Bronchitis bacterial	1/481 (0.2%)
H1N1 influenza	2/481 (0.4%)
Infective pulmonary exacerbation of cystic fibrosis	40/481 (8.3%)
Influenza	4/481 (0.8%)
Lower respiratory tract infection bacterial	1/481 (0.2%)
Mastoiditis	1/481 (0.2%)
Medical device site cellulitis	1/481 (0.2%)
Pneumonia	2/481 (0.4%)
Pneumonia pseudomonal	1/481 (0.2%)
Sepsis	1/481 (0.2%)
Tonsillitis	1/481 (0.2%)
Urinary tract infection	1/481 (0.2%)
Vascular device infection	2/481 (0.4%)
Injury, poisoning and procedural complications
Alcohol poisoning	1/481 (0.2%)
Contusion	1/481 (0.2%)
Craniocerebral injury	1/481 (0.2%)
Forearm fracture	1/481 (0.2%)
Intentional overdose	1/481 (0.2%)
Stoma site extravasation	1/481 (0.2%)
Toxicity to various agents	1/481 (0.2%)
Investigations
Alanine aminotransferase increased	4/481 (0.8%)
Aspartate aminotransferase increased	4/481 (0.8%)
Blood creatine phosphokinase increased	1/481 (0.2%)
Gamma-glutamyltransferase increased	2/481 (0.4%)
Pulmonary function test decreased	1/481 (0.2%)
Metabolism and nutrition disorders
Diabetes mellitus	1/481 (0.2%)
Diabetes mellitus inadequate control	1/481 (0.2%)
Hypoglycaemia	1/481 (0.2%)
Musculoskeletal and connective tissue disorders
Compartment syndrome	1/481 (0.2%)
Nervous system disorders
Seizure	2/481 (0.4%)
Syncope	1/481 (0.2%)
Product Issues
Device leakage	1/481 (0.2%)
Psychiatric disorders
Anxiety	1/481 (0.2%)
Breathing-related sleep disorder	1/481 (0.2%)
Delirium	1/481 (0.2%)
Suicidal ideation	1/481 (0.2%)
Renal and urinary disorders
Hydronephrosis	1/481 (0.2%)
Nephrolithiasis	3/481 (0.6%)
Pelvi-ureteric obstruction	1/481 (0.2%)
Respiratory, thoracic and mediastinal disorders
Granulomatous pneumonitis	1/481 (0.2%)
Haemoptysis	5/481 (1%)
Increased bronchial secretion	1/481 (0.2%)
Pleuritic pain	1/481 (0.2%)
Other (Not Including Serious) Adverse Events
	VX-659/TEZ/IVA TC
	Affected / at Risk (%)	# Events
Total	446/481 (92.7%)
Gastrointestinal disorders
Abdominal pain	42/481 (8.7%)
Abdominal pain upper	26/481 (5.4%)
Diarrhoea	42/481 (8.7%)
Nausea	36/481 (7.5%)
Vomiting	27/481 (5.6%)
General disorders
Fatigue	31/481 (6.4%)
Pyrexia	56/481 (11.6%)
Infections and infestations
Infective pulmonary exacerbation of cystic fibrosis	149/481 (31%)
Influenza	40/481 (8.3%)
Nasopharyngitis	97/481 (20.2%)
Sinusitis	30/481 (6.2%)
Upper respiratory tract infection	104/481 (21.6%)
Viral upper respiratory tract infection	38/481 (7.9%)
Investigations
Alanine aminotransferase increased	43/481 (8.9%)
Aspartate aminotransferase increased	42/481 (8.7%)
Blood creatine phosphokinase increased	37/481 (7.7%)
Nervous system disorders
Headache	51/481 (10.6%)
Respiratory, thoracic and mediastinal disorders
Cough	126/481 (26.2%)
Haemoptysis	39/481 (8.1%)
Nasal congestion	53/481 (11%)
Oropharyngeal pain	80/481 (16.6%)
Respiration abnormal	28/481 (5.8%)
Rhinorrhoea	40/481 (8.3%)
Sinus congestion	27/481 (5.6%)
Sputum increased	69/481 (14.3%)
Skin and subcutaneous tissue disorders
Rash	28/481 (5.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.