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TerminatedNCT03447262Updated Jan 25, 2022Results posted

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

A Phase 3 interventional study of VX-659/TEZ/IVA and IVA in Cystic Fibrosis, sponsored by Vertex Pharmaceuticals Incorporated. Terminated at 100 sites in 11 countries. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2022-01-25.

Sponsored by Vertex Pharmaceuticals Incorporated · Phase 3, Interventional, and Treatment

Why this study was terminated
At Sponsor's Discretion
Phase
Phase 3
Study type
Interventional
Enrollment
484
Allocation
Not applicable
Ages
12 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Cystic Fibrosis
03

Who can participate

Ages eligible
12 Years and older
Sexes eligible
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

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.

04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
484 participants (actual)

Study arms

  • 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 · Drug: IVA

Interventions

  • DrugVX-659/TEZ/IVA

    Fixed-dose combination tablets for oral administration qd in the morning.

    Also known as: VX-659/VX-661/VX-770, VX-659/tezacaftor/ivacaftor

  • DrugIVA

    IVA tablet qd in the evening.

    Also known as: VX-770, ivacaftor

05

What researchers measure

Primary outcomes

  1. 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)

Secondary outcomes

  1. Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102

    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)

  2. Absolute Change in ppFEV1 for Participants From the Parent Study 659-103

    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)

  3. Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102

    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)

  4. Absolute Change in SwCl for Participants From the Parent Study 659-103

    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)

  5. Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102

    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)

  6. Number of PEx for Participants From the Parent Study 659-103

    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)

  7. Number of Participants With at Least One PEx for Participants From the Parent Study 659-102

    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)

  8. Number of Participants With at Least One PEx for Participants From the Parent Study 659-103

    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)

  9. Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102

    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)

  10. Absolute Change in BMI for Participants From the Parent Study 659-103

    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)

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

    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)

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

    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)

  13. Absolute Change in Body Weight for Participants From the Parent Study 659-102

    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)

  14. Absolute Change in Body Weight for Participants From the Parent Study 659-103

    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)

  15. Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102

    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)

  16. Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103

    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)

06

Results

Posted Jan 25, 2022

Participant flow

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.

Participant flow — Overall Study
MilestoneVX-659/TEZ/IVA Triple Combination (TC)
Started481
Completed2
Not completed479
Withdrew: Adverse event7
Withdrew: Withdrawal of consent (not due to ae)2
Withdrew: Commercial drug is available for participant9
Withdrew: Death2
Withdrew: Study termination by sponsor455
Withdrew: Other4

Outcome measures

PrimarySafety 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)
Reported as:
Number · participants
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
participantsVX-659/TEZ/IVA TC
Participants With AEs470
Participants With SAEs99
SecondaryAbsolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102

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)
Reported as:
Mean · percentage points
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for Participants From the Parent Study 659-102
percentage pointsVX-659/TEZ/IVA TC
Placebo - VX-659/TEZ/IVA14.2 ± 7.8
VX-659/TEZ/IVA - VX-659/TEZ/IVA10.3 ± 9.3
SecondaryAbsolute Change in ppFEV1 for Participants From the Parent Study 659-103

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)
Reported as:
Mean · percentage points
Absolute Change in ppFEV1 for Participants From the Parent Study 659-103
percentage pointsVX-659/TEZ/IVA TC
TEZ/IVA - VX-659/TEZ/IVA15.1 ± 11.9
VX-659/TEZ/IVA - VX-659/TEZ/IVA11.5 ± 9.8
SecondaryAbsolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102

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)
Reported as:
Mean · millimole per liter (mmol/L)
Absolute Change in Sweat Chloride (SwCl) for Participants From the Parent Study 659-102
millimole per liter (mmol/L)VX-659/TEZ/IVA TC
Placebo - VX-659/TEZ/IVA-48.9 ± 20.4
VX-659/TEZ/IVA - VX-659/TEZ/IVA-49.7 ± 20.1
SecondaryAbsolute Change in SwCl for Participants From the Parent Study 659-103

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)
Reported as:
Mean · mmol/L
Absolute Change in SwCl for Participants From the Parent Study 659-103
mmol/LVX-659/TEZ/IVA TC
TEZ/IVA - VX-659/TEZ/IVA-45.7 ± 16.8
VX-659/TEZ/IVA - VX-659/TEZ/IVA-53.5 ± 16.2
SecondaryNumber of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102

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)
Reported as:
Number · PEx events
Number of Pulmonary Exacerbations (PEx) for Participants From the Parent Study 659-102
PEx eventsVX-659/TEZ/IVA TC
Placebo - VX-659/TEZ/IVA60
VX-659/TEZ/IVA - VX-659/TEZ/IVA84
SecondaryNumber of PEx for Participants From the Parent Study 659-103

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)
Reported as:
Number · PEx events
Number of PEx for Participants From the Parent Study 659-103
PEx eventsVX-659/TEZ/IVA TC
Number of PEx for Participants From the Parent Study 659-10339
SecondaryNumber of Participants With at Least One PEx for Participants From the Parent Study 659-102

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)
Reported as:
Number · participants
Number of Participants With at Least One PEx for Participants From the Parent Study 659-102
participantsVX-659/TEZ/IVA TC
Placebo - VX-659/TEZ/IVA43
VX-659/TEZ/IVA - VX-659/TEZ/IVA52
SecondaryNumber of Participants With at Least One PEx for Participants From the Parent Study 659-103

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)
Reported as:
Number · participants
Number of Participants With at Least One PEx for Participants From the Parent Study 659-103
participantsVX-659/TEZ/IVA TC
Number of Participants With at Least One PEx for Participants From the Parent Study 659-10328
SecondaryAbsolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102

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)
Reported as:
Mean · kilogram per meter square (kg/m^2)
Absolute Change in Body Mass Index (BMI) for Participants From the Parent Study 659-102
kilogram per meter square (kg/m^2)VX-659/TEZ/IVA TC
Placebo - VX-659/TEZ/IVA1.55 ± 1.35
VX-659/TEZ/IVA - VX-659/TEZ/IVA1.43 ± 1.94
SecondaryAbsolute Change in BMI for Participants From the Parent Study 659-103

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)
Reported as:
Mean · kg/m^2
Absolute Change in BMI for Participants From the Parent Study 659-103
kg/m^2VX-659/TEZ/IVA TC
TEZ/IVA - VX-659/TEZ/IVA1.16 ± 1.68
VX-659/TEZ/IVA - VX-659/TEZ/IVA0.90 ± 1.52
SecondaryAbsolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline)

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)
Reported as:
Mean · z-score
Absolute Change in BMI Z-score for Participants From the Parent Study 659-102 (Participants <=20 Years Old at Parent Study Baseline)
z-scoreVX-659/TEZ/IVA TC
Placebo - VX-659/TEZ/IVA0.22 ± 0.59
VX-659/TEZ/IVA - VX-659/TEZ/IVA0.10 ± 0.44
SecondaryAbsolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline)

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)
Reported as:
Mean · z-score
Absolute Change in BMI Z-score for Participants From The Parent Study 659-103 (Participants <=20 Years Old at Parent Study Baseline)
z-scoreVX-659/TEZ/IVA TC
TEZ/IVA - VX-659/TEZ/IVANA ± NA
VX-659/TEZ/IVA - VX-659/TEZ/IVANA ± NA
SecondaryAbsolute Change in Body Weight for Participants From the Parent Study 659-102

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)
Reported as:
Mean · kg
Absolute Change in Body Weight for Participants From the Parent Study 659-102
kgVX-659/TEZ/IVA TC
Placebo - VX-659/TEZ/IVA4.8 ± 4.4
VX-659/TEZ/IVA - VX-659/TEZ/IVA4.3 ± 5.6
SecondaryAbsolute Change in Body Weight for Participants From the Parent Study 659-103

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)
Reported as:
Mean · kg
Absolute Change in Body Weight for Participants From the Parent Study 659-103
kgVX-659/TEZ/IVA TC
TEZ/IVA - VX-659/TEZ/IVA3.7 ± 4.9
VX-659/TEZ/IVA - VX-659/TEZ/IVA3.2 ± 5.0
SecondaryAbsolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102

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)
Reported as:
Mean · units on a scale
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for Participants From the Parent Study 659-102
units on a scaleVX-659/TEZ/IVA TC
Placebo - VX-659/TEZ/IVA16.7 ± 18.7
VX-659/TEZ/IVA - VX-659/TEZ/IVA19.7 ± 17.4
SecondaryAbsolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103

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)
Reported as:
Mean · units on a scale
Absolute Change in CFQ-R Respiratory Domain Score for Participants From the Parent Study 659-103
units on a scaleVX-659/TEZ/IVA TC
TEZ/IVA - VX-659/TEZ/IVA17.1 ± 18.2
VX-659/TEZ/IVA - VX-659/TEZ/IVA16.9 ± 17.3

Adverse events

Collected over 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). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
VX-659/TEZ/IVA TC2/481 (0.4%)99/481 (20.6%)446/481 (92.7%)
Most frequent serious events
Showing 10 of 68
Most frequent serious events
EventVX-659/TEZ/IVA TC
Infective pulmonary exacerbation of cystic fibrosisInfections and infestations40/481
Distal intestinal obstruction syndromeGastrointestinal disorders6/481
HaemoptysisRespiratory, thoracic and mediastinal disorders5/481
InfluenzaInfections and infestations4/481
Alanine aminotransferase increasedInvestigations4/481
Aspartate aminotransferase increasedInvestigations4/481
Abdominal painGastrointestinal disorders3/481
NephrolithiasisRenal and urinary disorders3/481
ConstipationGastrointestinal disorders2/481
CholecystitisHepatobiliary disorders2/481
Most frequent other events
Showing 10 of 26
Most frequent other events
EventVX-659/TEZ/IVA TC
Infective pulmonary exacerbation of cystic fibrosisInfections and infestations149/481
CoughRespiratory, thoracic and mediastinal disorders126/481
Upper respiratory tract infectionInfections and infestations104/481
NasopharyngitisInfections and infestations97/481
Oropharyngeal painRespiratory, thoracic and mediastinal disorders80/481
Sputum increasedRespiratory, thoracic and mediastinal disorders69/481
PyrexiaGeneral disorders56/481
Nasal congestionRespiratory, thoracic and mediastinal disorders53/481
HeadacheNervous system disorders51/481
Alanine aminotransferase increasedInvestigations43/481

Baseline characteristics

Age, Continuous
Age, Continuous(years)VX-659/TEZ/IVA TC
Mean26.9 ± 9.7
Sex: Female, Male
Sex: Female, Male(Participants)VX-659/TEZ/IVA TC
Female219
Male262
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)VX-659/TEZ/IVA TC
Hispanic or Latino14
Not Hispanic or Latino462
Unknown or Not Reported5
Race (NIH/OMB)
Race (NIH/OMB)(Participants)VX-659/TEZ/IVA TC
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American3
White474
More than one race4
Unknown or Not Reported0
07

Study locations

100 sites
  • University of Alabama at Birmingham
    Birmingham, Alabama 35233, United States
  • Stanford University
    Palo Alto, California 94304, United States
  • Children's Hospital Colorado
    Aurora, Colorado 80045, United States
  • Hartford Hospital
    Hartford, Connecticut 06102, United States
  • Yale New Haven Medical Center
    New Haven, Connecticut 06511, United States
  • University of Miami Miller School of Medicine
    Miami, Florida 33136, United States
  • Nicklaus Children's Hospital
    Miami, Florida 33155, United States
  • Orlando Health, Inc.- Arnold Palmer Hospital for Children (APH)
    Orlando, Florida 32806, United States
  • Johns Hopkins All Children's Hospital Outpatient Care Center
    Saint Petersburg, Florida 33701, United States
  • St. Luke's CF Center of Idaho
    Boise, Idaho 83712, United States
  • Cystic Fibrosis Center of Chicago
    Glenview, Illinois 60025, United States
  • Advocate Children's Hospital - Park Ridge / North Suburban Pulmonary and Critical Care Consultants
    Niles, Illinois 60714, United States
  • Indiana Clinical Research Center, IU Health University Hospital
    Indianapolis, Indiana 46202, United States
  • The University of Iowa Hospitals and Clinics
    Iowa City, Iowa 52242, United States
  • University of Kentucky
    Lexington, Kentucky 40536, United States
  • Kosair Charities Pediatric Clinical Research Unit
    Louisville, Kentucky 40202, United States
  • Johns Hopkins Hospital
    Baltimore, Maryland 21287, United States
  • Boston Children's Hospital
    Boston, Massachusetts 02115, United States
  • UMass Memorial Medical Center
    Worcester, Massachusetts 01655, United States
  • Michigan Medicine
    Ann Arbor, Michigan 48109-5212, United States
  • Spectrum Health Medical Group Adult Cystic Fibrosis Care Center
    Grand Rapids, Michigan 49546, United States
  • University of Minnesota
    Minneapolis, Minnesota 55455, United States
  • University of Mississippi Medical Center
    Jackson, Mississippi 39216, United States
  • The Children's Mercy Hospital
    Kansas City, Missouri 64108, United States
  • Washington University School of Medicine/ St. Louis Children's Hospital
    Saint Louis, Missouri 63110, United States
  • Dartmouth Hitchcock, Manchester
    Manchester, New Hampshire 03104, United States
  • Rutgers-Robert Wood Johnson Medical School
    New Brunswick, New Jersey 08901, United States
  • Albany Medical College
    Albany, New York 12208, United States
  • CF Therapeutics Development Center of Western New York
    Buffalo, New York 14203, United States
  • Northwell Health, Long Island Jewish Medical Center
    New Hyde Park, New York 11040, United States
  • Columbia University Medical Center
    New York, New York 10032, United States
  • SUNY Upstate Medical University
    Syracuse, New York 13210, United States
  • Clinical Research of Charlotte
    Charlotte, North Carolina 28277, United States
  • Duke University Medical Center
    Durham, North Carolina 27710, United States
  • Cincinnati Children's Hospital
    Cincinnati, Ohio 45229, United States
  • Santiago Reyes, M.D.
    Oklahoma City, Oklahoma 73112, United States
  • Oregon Health & Science University
    Portland, Oregon 97239, United States
  • Drexel University College of Medicine / Drexel Adult Cystic Fibrosis Center
    Philadelphia, Pennsylvania 19107, United States
  • Children's Hospital of Pittsburgh of UPMC
    Pittsburgh, Pennsylvania 15224, United States
  • Sanford Children's Specialty Clinic
    Sioux Falls, South Dakota 57105, United States
  • University of Tennessee Medical Center- Adult Cystic Fibrosis Clinic
    Knoxville, Tennessee 37920, United States
  • Children's Foundation Research Center / Le Bonheur Children's Hospital
    Memphis, Tennessee 38103, United States
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37232, United States
  • Cook Children's Medical Center
    Fort Worth, Texas 76104, United States
  • Texas Children's Hospital
    Houston, Texas 77030, United States
  • University of Utah/ Primary Children's Medical Center
    Salt Lake City, Utah 84132, United States
  • Seattle Children's Hospital
    Seattle, Washington 98105, United States
  • Providence Pediatric Pulmonary & Cystic Fibrosis Clinic
    Spokane, Washington 99204, United States
  • Royal Adelaide Hospital
    Adelaide, Australia
  • The Prince Charles Hospital
    Chermside, Australia
  • Alfred Hospital
    Melbourne, Australia
  • Institute for Respiratory Health, Sir Charles Gairdner Hospital
    Nedlands, Australia
  • John Hunter Hospital & Hunter Medical Research Institute and John Hunter Children's Hospital
    New Lambton, Australia
  • Telethon Kids Institute
    Perth, Australia
  • Sydney Children's Hospital
    Randwick, Australia
  • Lady Cilento Children's Hospital
    South Brisbane, Australia
  • Stollery Children's Hospital
    Edmonton, Canada
  • Queen Elizabeth II Health Sciences Center
    Halifax, Canada
  • St. Michael's Hospital
    Toronto, Canada
  • Juliane Marie Center, Rigshospitalet
    Copenhagen, Denmark
  • Charite Paediatric Pulmonology Department
    Berlin, Germany
  • Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
    Essen, Germany
  • Clinic of J.W. Goethe University
    Frankfurt, Germany
  • Medizinische Hochschule Hannover
    Hannover, Germany
  • Mukeviszidose-Zentrum am Universitatsklinikum Jena, Klinik fuer Kinder- und Jugendmedizin
    Jena, Germany
  • Universitaetsklinkum Koeln, CF-Studienzentrum
    Koeln, Germany
  • Universitatsklinikum Schleswig-Holstein, Klinik für Kinder- und Jugendmedizin
    Lubeck, Germany
  • Pneumologische Praxis Pasing
    Muenchen, Germany
  • Klinikum Innenstadt, University of Munich
    München, Germany
  • Cork University Hospital
    Cork, Ireland
  • Beaumont Hospital
    Dublin, Ireland
  • Our Lady's Children's Hospital
    Dublin, Ireland
  • St. Vincent's University Hospital
    Dublin, Ireland
  • Temple Street Children's University Hospital
    Dublin, Ireland
  • University Hospital Galway
    Galway, Ireland
  • University Hospital Limerick
    Limerick, Ireland
  • Lady Davis Carmel Medical Center
    Haifa, Israel
  • Rambam Health Care Campus, Liver Unit
    Haifa, Israel
  • Pediatrics Hadassah Medical Center
    Jerusalem, Israel
  • Schneider Children's Medical Center
    Petah Tikva, Israel
  • Sheba Medical Center
    Tel HaShomer, Israel
  • Klinika Mukowiscydozy IMD Oddozial Chorob Pluc Szpzoz IM. Dzieci WarszaWY
    Łomianki, Poland
  • Hospital Universitari Vall d Hebron
    Barcelona, Spain
  • Hospital Universitari Vall d´Hebron Servicio de Broncoscopia
    Barcelona, Spain
  • Hospital Universitario 12 de Octubre
    Madrid, Spain
  • Hospital Universitario Infantil La Paz
    Madrid, Spain
  • Parc Tauli Sabadell Hospital Universitari
    Sabadell, Spain
  • Hospital Universitario Virgen del Rocio
    Sevilla, Spain
  • Hospital Universitario y Politecnico La Fe
    Valencia, Spain
  • Lindenhofspital - Quartier Bleu
    Bern, Switzerland
  • Kinderspital Zuerich
    Zürich, Switzerland
  • Papworth Hospital NHS Foundation Trust, Papworth Everard
    Cambridge, United Kingdom
  • Clinical Research Facility, Queen Elizabeth University Hospital
    Glasgow, United Kingdom
  • St. James University Hospital
    Leeds, United Kingdom
  • Liverpool Head and Chest Hospital
    Liverpool, United Kingdom
  • Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
    London, United Kingdom
  • Wythenshaw e Hospital
    Manchester, United Kingdom
  • The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
    Newcastle Upon Tyne, United Kingdom
  • Wolfson Cystic Fibrosis Unit, City Campus
    Nottingham, United Kingdom
  • All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
    Penarth, United Kingdom
08

References and documents

Publications

  • Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3. PubMed 33331662 ↗

Study documents

  • Study protocol · Oct 23, 2018
  • Statistical analysis plan · Feb 4, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03447262
Lead sponsor
Vertex Pharmaceuticals Incorporated
Responsible party
Sponsor
First posted
Feb 27, 2018
Start date
Jul 13, 2018
Primary completion
Sep 9, 2020
Completion
Sep 9, 2020
Results posted
Jan 25, 2022
Last update
Jan 25, 2022

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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