Cystic Fibrosis
Conditions
Brief summary
The primary objective of the study was to evaluate the safety of long-term VX-770 treatment in participants with cystic fibrosis (CF). The secondary objective of the study was to evaluate the efficacy of long-term VX-770 treatment in subjects with CF.
Detailed description
This open-label, rollover study of orally administered VX-770 was conducted in participants with CF to evaluate the safety and efficacy of long-term VX-770 treatment. Participants who were previously enrolled in Study 102 (VX08-770-102/NCT00909532) and Study 103 (VX08-770-103/NCT00909727), and met certain criteria were eligible to enroll in this study (Study 105/VX08-770-105/NCT01117012).
Interventions
DRUGIvacaftor
Sponsors
Cystic Fibrosis Foundation
Vertex Pharmaceuticals Incorporated
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants who have completed the assigned study treatment in Study 102 or Study 103 2. Participants who are females of childbearing potential must have a negative urine pregnancy test on Day 1 (first dose of VX-770) 3. Participants who are able to understand and comply with protocol requirements, restrictions, and instructions and likely to complete the study as planned, as judged by the investigator 4. Participants of child bearing potential and who are sexually active must meet the contraception requirements 5. Participants must sign the informed consent form (ICF), and where appropriate, assent must be obtained
Exclusion criteria
1. Participants with a history of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject 2. Participants with a history of study treatment intolerance as observed in their previous VX-770 study that, in the opinion of the investigator, might pose an additional risk in administering study drug to the subject 3. Participants who are pregnant, planning a pregnancy, breast-feeding, or not willing to follow contraception requirements 4. Participants taking any inhibitors or inducers of Cytochrome P450 3A4 (CYP3A4), including certain herbal medications (for example, St. John's Wort) and grapefruit/grapefruit juice
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | Study 105: Day 1 up to Week 168 | Adverse Event: any untoward medical occurrence in a participant during the study, including any unfavorable and unintended sign, symptom, or disease whether or not it was considered to be study drug related. This included any newly occurring event or previous condition that increased in severity or frequency after obtaining informed consent and assent (where applicable). SAE: medical event or condition, which resulted in any of following, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Non-Serious AEs included all AEs except SAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Study 105 Baseline in Percent Predicted FEV1 Through Week 96 | Study 105: Baseline through Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in Study 105. Absolute Change at Week 48 and Week 96 are reported. |
| Absolute Change From Study 105 Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 96 | Study 105: Baseline through Week 96 | The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Absolute Change at Week 48 and Week 96 are reported. |
| Annualized Rate of Decline From Study 105 Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 96 | Study 105: Baseline through Week 96 | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method. Baseline was defined as Study 105 Day 15. |
| Annualized Duration of Pulmonary Exacerbation Events | Study 105: Day 1 through Week 96 | — |
| Absolute Change From Study 105 Baseline in Weight Through Week 96 | Study 105: Baseline through Week 96 | Weight is a measurement of nutritional status. Absolute change in weight, measured in kilograms (kg), at Week 48 and Week 96 are reported. |
| Annualized Pulmonary Exacerbation Event Rate | Study 105: Day 1 through Week 96 | Annualized event rate was calculated by regression with negative binomial distribution. |
Countries
Australia, Canada, Czechia, France, Germany, Ireland, United Kingdom, United States
Participant flow
Recruitment details
Participants with Cystic Fibrosis (CF) who had completed the Study VX08-770-102 (Study 102/NCT00909532) and Study VX08-770-103 (Study 103/NCT00909727), were enrolled in this Study VX08-770-105 (Study 105/NCT01117012).
Pre-assignment details
A total of 192 subjects were enrolled. Efficacy results are presented as per the treatment received in previous study (Placebo/Ivacaftor \[VX-770\]).
Participants by arm
| Arm | Count |
|---|---|
| Placebo/VX-770 Participants who received placebo during the parent study (Study 102 or 103), received VX-770 150 mg tablet orally q12h. | 89 |
| VX-770/VX-770 Participants who received VX-770 during the parent study (Study 102 or 103), received VX-770 150 mg tablet orally q12h. | 103 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Undefined | 4 | 3 |
| Overall Study | Withdrawal by Subject | 3 | 0 |
Baseline characteristics
| Characteristic | Placebo/VX-770 | VX-770/VX-770 | Total |
|---|---|---|---|
| Age, Continuous | 22.0 years STANDARD_DEVIATION 10.94 | 23.2 years STANDARD_DEVIATION 11.55 | 22.6 years STANDARD_DEVIATION 11.26 |
| Sex: Female, Male Female | 44 Participants | 58 Participants | 102 Participants |
| Sex: Female, Male Male | 45 Participants | 45 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 190 / 192 |
| serious Total, serious adverse events | 70 / 192 |
Outcome results
Primary
Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Adverse Event: any untoward medical occurrence in a participant during the study, including any unfavorable and unintended sign, symptom, or disease whether or not it was considered to be study drug related. This included any newly occurring event or previous condition that increased in severity or frequency after obtaining informed consent and assent (where applicable). SAE: medical event or condition, which resulted in any of following, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolonged hospitalization, persistent/significant disability/incapacity, congenital anomaly/birth defect, important medical event. Non-Serious AEs included all AEs except SAEs.
Time frame: Study 105: Day 1 up to Week 168
Population: Safety Set included all participants who received at least 1 dose of study drug during Study 105.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| VX-770 | Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | Non-Serious AEs | 190 participants |
| VX-770 | Number of Participants With Non-Serious Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 70 participants |
Secondary
Absolute Change From Study 105 Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 96
The CFQ-R is a validated patient-reported outcome measuring health-related quality of life for subjects with cystic fibrosis. Respiratory domain assessed respiratory symptoms (for example, coughing, congestion, wheezing), score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. Absolute Change at Week 48 and Week 96 are reported.
Time frame: Study 105: Baseline through Week 96
Population: Full Analysis Set. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure and n signifies participants who were evaluable for specified categories for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-770 | Absolute Change From Study 105 Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 96 | Absolute Change at Week 48 (n = 86, 99) | 7.43 units on a scale | Standard Deviation 16.6 |
| VX-770 | Absolute Change From Study 105 Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 96 | Absolute Change at Week 96 (n = 77, 97) | 10.05 units on a scale | Standard Deviation 15.254 |
| VX-770/VX-770 | Absolute Change From Study 105 Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 96 | Absolute Change at Week 48 (n = 86, 99) | -1.94 units on a scale | Standard Deviation 16.55 |
| VX-770/VX-770 | Absolute Change From Study 105 Baseline in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 96 | Absolute Change at Week 96 (n = 77, 97) | 0.77 units on a scale | Standard Deviation 14.305 |
Secondary
Absolute Change From Study 105 Baseline in Percent Predicted FEV1 Through Week 96
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in Study 105. Absolute Change at Week 48 and Week 96 are reported.
Time frame: Study 105: Baseline through Week 96
Population: Full Analysis Set. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure and n signifies participants who were evaluable for specified categories for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-770 | Absolute Change From Study 105 Baseline in Percent Predicted FEV1 Through Week 96 | Absolute Change at Week 48 (n = 85, 99) | 9.2585 percent predicted of FEV1 | Standard Deviation 9.63822 |
| VX-770 | Absolute Change From Study 105 Baseline in Percent Predicted FEV1 Through Week 96 | Absolute Change at Week 96 (n = 76, 97) | 9.8194 percent predicted of FEV1 | Standard Deviation 11.22812 |
| VX-770/VX-770 | Absolute Change From Study 105 Baseline in Percent Predicted FEV1 Through Week 96 | Absolute Change at Week 48 (n = 85, 99) | -0.4422 percent predicted of FEV1 | Standard Deviation 8.62332 |
| VX-770/VX-770 | Absolute Change From Study 105 Baseline in Percent Predicted FEV1 Through Week 96 | Absolute Change at Week 96 (n = 76, 97) | 0.1581 percent predicted of FEV1 | Standard Deviation 9.01629 |
Secondary
Absolute Change From Study 105 Baseline in Weight Through Week 96
Weight is a measurement of nutritional status. Absolute change in weight, measured in kilograms (kg), at Week 48 and Week 96 are reported.
Time frame: Study 105: Baseline through Week 96
Population: Full Analysis Set. Here, number of participants analyzed signifies participants who were evaluable for this outcome measure and n signifies participants who were evaluable for specified categories for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| VX-770 | Absolute Change From Study 105 Baseline in Weight Through Week 96 | Absolute Change at Week 48 (n = 86, 99) | 4.03 kg | Standard Deviation 3.677 |
| VX-770 | Absolute Change From Study 105 Baseline in Weight Through Week 96 | Absolute Change at Week 96 (n = 76, 97) | 4.93 kg | Standard Deviation 5.577 |
| VX-770/VX-770 | Absolute Change From Study 105 Baseline in Weight Through Week 96 | Absolute Change at Week 48 (n = 86, 99) | 1.26 kg | Standard Deviation 3.844 |
| VX-770/VX-770 | Absolute Change From Study 105 Baseline in Weight Through Week 96 | Absolute Change at Week 96 (n = 76, 97) | 2.62 kg | Standard Deviation 5.909 |
Secondary
Annualized Duration of Pulmonary Exacerbation Events
Time frame: Study 105: Day 1 through Week 96
Population: Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VX-770 | Annualized Duration of Pulmonary Exacerbation Events | 10.89 Days per year | Standard Deviation 20.124 |
| VX-770/VX-770 | Annualized Duration of Pulmonary Exacerbation Events | 17.27 Days per year | Standard Deviation 30.974 |
Secondary
Annualized Pulmonary Exacerbation Event Rate
Annualized event rate was calculated by regression with negative binomial distribution.
Time frame: Study 105: Day 1 through Week 96
Population: Full Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VX-770 | Annualized Pulmonary Exacerbation Event Rate | 0.463 events per year |
| VX-770/VX-770 | Annualized Pulmonary Exacerbation Event Rate | 0.658 events per year |
Secondary
Annualized Rate of Decline From Study 105 Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 96
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. Predicted FEV1 (for age, gender, and height) was calculated using the Knudson method. Baseline was defined as Study 105 Day 15.
Time frame: Study 105: Baseline through Week 96
Population: Full Analysis Set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| VX-770 | Annualized Rate of Decline From Study 105 Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 96 | -0.30 percent predicted of FEV1 per year |
| VX-770/VX-770 | Annualized Rate of Decline From Study 105 Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1) Through Week 96 | -1.23 percent predicted of FEV1 per year |