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

Primary Purpose

Cystic Fibrosis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

TEZ/IVA

IVA

About this trial

This is an interventional treatment trial for Cystic Fibrosis

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Part A:

Subjects entering the Treatment Cohort must meet all of the following criteria:
Elect to enroll in the Treatment Cohort
Completed study drug Treatment Period in a parent study (NCT02070744, NCT02347657, NCT02516410, NCT02392234, NCT02412111) or study drug treatment and the Safety Follow up Visit for subjects from NCT02508207.
Willing to remain on a stable CF regimen through the Safety Follow-up Visit.
Subjects re-enrolling in the Part A Treatment Cohort must meet all of the following criteria:
- Previously received at least 4 weeks of study drug before discontinuing in Part A of Study NCT02565914 to participate in another qualified Vertex study.
- Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part A Study NCT02565914.
Subjects entering the Part A Observational Cohort must meet the following criteria:
- <18 years of age (age on the date of informed consent/assent in the parent study)
- Completed study drug Treatment Period in a parent study or study drug treatment and the Safety Follow up Visit for subjects from NCT02508207, but do not elect to enroll in the NCT02565914 Treatment Cohort; or
- Received at least 4 weeks of study drug treatment and completed visits up to the last scheduled visit of the Treatment Period of a parent study (and the Safety Follow up Visit for subjects from NCT02508207), but do not meet eligibility criteria for enrollment into the Treatment Cohort

Part B:

Subjects who meet all of the following inclusion criteria will be eligible for Part B.

Did not withdraw consent from the parent study or Part A of Study NCT02565914.
Completed study drug treatment during the Treatment Period in Part A of - Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Study NCT02565914.

Subjects re enrolling in Part B must meet all of the following criteria:

Previously received at least 4 weeks of study drug before discontinuing Study NCT02565914 to participate in another qualified Vertex study, which is defined as a Vertex study of investigational CFTR modulators that allows participation of subjects in Study NCT02565914.
Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part B.
Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit in Part B.

Part C:

Subjects who meet all of the following inclusion criteria will be eligible for Part C.
Did not withdraw consent from Part B of Study NCT02565914.
Completed study drug treatment during Part B of NCT02565914.
Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Part C.

Exclusion Criteria:

History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject.
Pregnant and nursing females.
Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements.
History of drug intolerance in the parent study that would pose an additional risk to the subject.
Participation in an investigational drug trial (including studies investigating VX-661/ivacaftor or lumacaftor/ivacaftor) other than the parent studies of NCT02565914 or other eligible Vertex studies investigating VX-661 in combination with ivacaftor, or use of a commercially available CFTR modulator.

Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TEZ/IVA

Arm Description

Part A: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 103,106,107,108,109 and 111 were administered TEZ 100 milligram (mg)/IVA 150 mg fixed-dose tablet in the morning and IVA 150 mg mono tablet in the evening for 96 weeks. Part B: Participants who received either TEZ/IVA, IVA monotherapy or Placebo in parent studies 106,108,109,112 and 114 were 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. Part C: Participants who received TEZ/IVA, IVA monotherapy or Placebo in parent studies 106,108, and 114 were administered TEZ 100 mg/IVA 150 mg fixed dose tablet in the morning and IVA 150 mg mono tablet in the evening for 192 weeks.

Outcomes

Primary Outcome Measures

Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs

Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Secondary Outcome Measures

Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set

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.

Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set

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.

Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set

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.

Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set

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.

Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set

Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set

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.

Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set

Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set

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.

Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set

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.

Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set

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.

Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set

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.

Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set

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.

Part A: Absolute Change in Body Mass Index (BMI) for 103/110 Efficacy Set

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.

Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set

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.

Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set

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.

Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set

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.

Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set

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.

Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set

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.

Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/110 Efficacy Set

Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set

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.

Part A: Absolute Change in Body Weight for 108/110 Efficacy Set

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.

Part A: Absolute Change in Body Weight for 103/110 Efficacy Set

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.

Part A: Absolute Change in Body Weight for 111/110 Efficacy Set

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.

Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set

Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set

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.

Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set

Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set

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.

Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set

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.

Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set

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.

Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA)

Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Part B: Absolute Change in Body Mass Index (BMI)

BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).

Part B: Absolute Change in BMI Z-score

Part B: Number of Pulmonary Exacerbation (PEx) Events

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.

Full Information

NCT ID

NCT02565914

First Posted

September 18, 2015

Last Updated

September 1, 2023

Sponsor

Vertex Pharmaceuticals Incorporated

1. Study Identification

Unique Protocol Identification Number

NCT02565914

Brief Title

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

Official Title

A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long Term Treatment With VX-661 in Combination With Ivacaftor in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous or Heterozygous for the F508del-CFTR Mutation

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

August 2015 (Actual)

Primary Completion Date

May 2019 (Actual)

Study Completion Date

December 5, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vertex Pharmaceuticals Incorporated

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a Phase 3, multicenter, open-label, 3-part rollover study in subjects with CF who are homozygous or heterozygous for the F508del-CFTR mutation and who participated in studies VX13-661-103 (Study 103, NCT02070744), VX14-661-106 (Study 106, NCT02347657), VX14-661-107 (Study 107, NCT02516410), VX14-661-108 (Study 108, NCT02392234), VX14-661-109 (Study 109, NCT02412111), VX14-661-111 (Study 111, NCT02508207), VX15-661-112 (NCT02730208), and VX16-661-114 (NCT03150719). The study is designed to evaluate the safety and efficacy of long-term treatment of VX-661 in combination with ivacaftor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1131 (Actual)

8. Arms, Groups, and Interventions

Arm Title

TEZ/IVA

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

TEZ/IVA

Other Intervention Name(s)

VX-661/VX-770, tezacaftor/ivacaftor

Intervention Description

Fixed dose tablet for oral administration.

Intervention Type

Drug

Intervention Name(s)

IVA

Other Intervention Name(s)

VX-770, ivacaftor

Intervention Description

Tablet for oral administration.

Primary Outcome Measure Information:

Title

Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time Frame

Day 1 up to Week 100

Title

Part B: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs

Time Frame

Day 1 up to Week 100

Title

Part C: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Time Frame

Day 1 up to Week 196

Secondary Outcome Measure Information:

Title

Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set

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

Title

Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set

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

Title

Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 106/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 108/110 Efficacy Set

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

Title

Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 103/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Relative Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for 111/110 Efficacy Set

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

Title

Part A: Number of Pulmonary Exacerbation (PEx) Events for 106/110 PEx Analysis Set

Description

Time Frame

From Baseline up to Study 110 Week 96

Title

Part A: Number of Pulmonary Exacerbation (PEx) Events for 108/110 PEx Analysis Set

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

Title

Part A: Absolute Change in Body Mass Index (BMI) for 106/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Body Mass Index (BMI) for 108/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Body Mass Index (BMI) for 103/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Body Mass Index (BMI) for Study 111/110 Efficacy Set

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

Title

Part A: Absolute Change in BMI Z-score for 106/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in BMI Z-score for 108/110 Efficacy Set

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

Title

Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 106/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change From Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 108/110 Efficacy Set

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

Title

Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 103/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Body Weight for Study 106/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Body Weight for 108/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Body Weight for 103/110 Efficacy Set

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

Title

Part A: Absolute Change in Body Weight for 111/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Body Weight Z-score for 106/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Body Weight Z-score for 108/110 Efficacy Set

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

Title

Part A: Absolute Change in Height Z-score for 106/110 Efficacy Set

Description

Time Frame

From Baseline at Study 110 Week 96

Title

Part A: Absolute Change in Height Z-score for 108/110 Efficacy Set

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

Title

Part A: Time-to-first Pulmonary Exacerbation (PEx) for 106/110 PEx Analysis Set

Description

Time Frame

96 weeks

Title

Part A: Time-to-first Pulmonary Exacerbation (PEx) for 108/110 PEx Analysis Set

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

Title

Part A: Plasma Concentrations of TEZ, TEZ Metabolite (M1-TEZ), Ivacaftor (IVA) and Ivacaftor Metabolite (M1-IVA)

Time Frame

Week 24

Title

Part B: Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

Description

FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.

Time Frame

From Baseline at Study 110 Week 96

Title

Part B: Absolute Change in Body Mass Index (BMI)

Description

BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).

Time Frame

From Baseline at Week 96

Title

Part B: Absolute Change in BMI Z-score

Description

Time Frame

From Baseline at Week 96

Title

Part B: Number of Pulmonary Exacerbation (PEx) Events

Description

Pulmonary exacerbation was defined as the treatment with new or changed antibiotic therapy (intravenous, inhaled, or oral) for greater than or equal to 4 sinopulmonary signs/symptoms.

Time Frame

From Baseline up to Week 96

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Part A: Participants entering the Treatment Cohort must meet all of the following criteria: Elect to enroll in the Treatment Cohort Completed study drug Treatment Period in a parent study (NCT02070744, NCT02347657, NCT02516410, NCT02392234, NCT02412111) or study drug treatment and the Safety Follow up Visit for participants from NCT02508207. Willing to remain on a stable CF regimen through the Safety Follow-up Visit. Participants re-enrolling in the Part A Treatment Cohort must meet all of the following criteria: Previously received at least 4 weeks of study drug before discontinuing in Part A of Study NCT02565914 to participate in another qualified Vertex study. Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part A Study NCT02565914. Participants entering the Part A Observational Cohort must meet the following criteria: <18 years of age (age on the date of informed consent/assent in the parent study) Completed study drug Treatment Period in a parent study or study drug treatment and the Safety Follow up Visit for subjects from NCT02508207, but do not elect to enroll in the NCT02565914 Treatment Cohort; or Received at least 4 weeks of study drug treatment and completed visits up to the last scheduled visit of the Treatment Period of a parent study (and the Safety Follow up Visit for participants from NCT02508207), but do not meet eligibility criteria for enrollment into the Treatment Cohort Part B: Participants who meet all of the following inclusion criteria will be eligible for Part B. Did not withdraw consent from the parent study or Part A of Study NCT02565914. Completed study drug treatment during the Treatment Period in Part A of - Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Study NCT02565914. Participants re enrolling in Part B must meet all of the following criteria: Previously received at least 4 weeks of study drug before discontinuing Study NCT02565914 to participate in another qualified Vertex study, which is defined as a Vertex study of investigational CFTR modulators that allows participation of participants in Study NCT02565914. Completed the last required visit of another qualified Vertex study before or during the Returning Visit in Part B. Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit in Part B. Part C: Participants who meet all of the following inclusion criteria will be eligible for Part C. Did not withdraw consent from Part B of Study NCT02565914. Completed study drug treatment during Part B of NCT02565914. Willing to remain on a stable CF medication (and supplement) regimen through the 96 week visit of Part C. Exclusion Criteria: History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject. Pregnant and nursing females. Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements. History of drug intolerance in the parent study that would pose an additional risk to the subject. Participation in an investigational drug trial (including studies investigating VX-661/ivacaftor or lumacaftor/ivacaftor) other than the parent studies of NCT02565914 or other eligible Vertex studies investigating VX-661 in combination with ivacaftor, or use of a commercially available CFTR modulator. Other protocol defined Inclusion/Exclusion criteria may apply.

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Gent

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Toronto

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Ontario

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Montréal

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Copenhagen

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Benite Cedex

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Bordeaux Cedex

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Bron Cedex

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France

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Lille

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Marseilles

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Montpellier Cedex 5

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France

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Paris Cedex 14

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France

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Paris Cedex 15

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France

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Paris

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France

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Rennes Cedex

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France

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Roscoff Cedex

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France

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Rouen Cedex

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France

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Berlin

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Germany

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Bochum

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Germany

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Erlangen

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Essen

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Frankfurt

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Germany

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Giesen

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Hannöver

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Heidelberg

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Munchen

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Tuebingen

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Dublin 4

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Ireland

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Dublin

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Limerick

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Ireland

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Haifa

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NAP

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Israel

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Haifa

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Israel

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Jerusalem

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Israel

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Petah Tikva

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Israel

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Tel Hashomer

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Israel

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Ancona

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Italy

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Genova

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Italy

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Milano

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Italy

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Orbassano

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Italy

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Palermo

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Italy

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Potenza

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Italy

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Roma

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Italy

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Rome

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Italy

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Torino

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Italy

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Verona

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Italy

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Amsterdam

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Netherlands

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Den Haag

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Netherlands

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Heidelberglaan

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Nijmegen

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Rotterdam

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Barcelona

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Madrid

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Sabadell

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Sevilla

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Valencia

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Goteborg

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Sweden

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Stockholm

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Sweden

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Uppsala

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Sweden

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Bern

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Switzerland

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Zurich

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Switzerland

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Leeds

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West Yorkshire

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United Kingdom

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Belfast

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United Kingdom

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Birmingham

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United Kingdom

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Exeter

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Glasgow

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Leeds

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Liverpool

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London

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Manchester

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Newcastle Upon Tyne

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United Kingdom

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Penarth

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United Kingdom

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Sheffield

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United Kingdom

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Southampton

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United Kingdom

City

Stoke-on-Trent

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United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

33581080

Citation

Flume PA, Biner RF, Downey DG, Brown C, Jain M, Fischer R, De Boeck K, Sawicki GS, Chang P, Paz-Diaz H, Rubin JL, Yang Y, Hu X, Pasta DJ, Millar SJ, Campbell D, Wang X, Ahluwalia N, Owen CA, Wainwright CE; VX14-661-110 study group. Long-term safety and efficacy of tezacaftor-ivacaftor in individuals with cystic fibrosis aged 12 years or older who are homozygous or heterozygous for Phe508del CFTR (EXTEND): an open-label extension study. Lancet Respir Med. 2021 Jul;9(7):733-746. doi: 10.1016/S2213-2600(20)30510-5. Epub 2021 Feb 10. Erratum In: Lancet Respir Med. 2021 Apr;9(4):e38.

Results Reference

derived

Learn more about this trial

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

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