Cystic Fibrosis
Conditions
Brief summary
This study is a Phase 2, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of CTX-4430 administered once-daily for 48 weeks for treatment of CF.
Detailed description
This study is a Phase 2, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of CTX-4430 administered once-daily for 48 weeks for treatment of CF. A total of 195 pulmonary CF patients that meet all the inclusion and no exclusion criteria and provide written informed consent will be randomized to receive 50 mg CTX-4430, 100 mg CTX-4430, or placebo in a 1:1:1 ratio. Follow-up visits will be conducted approximately every 4 weeks from Week 4 to Week 52 (4 weeks after completion of treatment).
Interventions
DRUGCTX-4430
DRUGPlacebo
Sponsors
Celtaxsys, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
No
Inclusion criteria
* Forced expiratory volume at one second (FEV1) ≥50 percent predicted at Screening * At least 1 pulmonary exacerbation in the 12 months before Screening
Exclusion criteria
* Pregnant or nursing women * Medical condition that is unstable, could be adversely impacted by participation in the study, or could impact assessment of the study results * History of organ transplantation * History of alcoholism or drug abuse within 2 years before Screening * Regular use of a high-dose NSAID within 60 days before Screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference From Placebo in Absolute Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted (ppFEV1) | Baseline, Week 48 | Difference from Placebo in absolute change from Baseline at Week 48 was assessed for FEV1 percent predicted. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Pulmonary Exacerbations Through 48 Weeks | Week 48 | Rate of protocol-defined pulmonary exacerbations reported through the Week 48/Early Termination visit will be annualized where a year is defined by 52 weeks and will be analyzed using a negative binomial regression. |
| Change From Baseline for C-reactive Protein (Hs-CRP) | Baseline, Week 48 | Results were only calculated in subjects who had a verifiable result at the Baseline and Week 48 visits. |
| Hazard Ratio Pulmonary Exacerbation While in the Study | Week 48 | Hazard Ratio of pulmonary exacerbation versus placebo for all subjects. Pulmonary exacerbations are defined as treatment with oral, inhaled, or intravenous antibiotic(s) for ≥4 of symptoms/signs per the modified Fuchs criteria. |
| Subjects Without a Pulmonary Exacerbation While in the Study | Week 48 | Subjects who did not experience a protocol-defined pulmonary exacerbation during the study |
| Relative Change (Percent Change) From Baseline in ppFEV1 | Baseline, Week 48 | Percent change from Baseline for ppFEV1 at 48 weeks was assessed. |
| Change From Baseline at 48 Weeks for Forced Vital Capacity Percent Predicted (FVC) and FEF25-75% (Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity) Percent Predicted | Baseline, Week 48 | — |
| Change From Baseline for Specified Biomarkers | Baseline, Week 48 | Results were only calculated in subjects who had a verifiable result at the Baseline and Week 48 visits. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Subjects Without a Pulmonary Exacerbation by Participants With ppFEV1 >75 at Baseline | Week 48 | Subjects who did not experience a protocol-defined pulmonary exacerbation during the study. |
| Number of Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | Week 48 | Rate of protocol-defined pulmonary exacerbations reported through the Week 48/Early Termination visit will be annualized where a year is defined by 52 weeks and will be analyzed using a negative binomial regression. |
| Hazard Ratio Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | Week 48 | Hazard Ratio pulmonary exacerbation versus placebo for all subjects taking CFTR-modulating therapy at Baseline |
| Subjects Without a Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | Week 48 | Subjects who did not experience a protocol-defined pulmonary exacerbation during the study. |
| Hazard Ratio Pulmonary Exacerbation for Participants With ppFEV1 >75 at Baseline | Week 48 | Hazard ratio of pulmonary exacerbation versus placebo for all subjects |
| Number of Pulmonary Exacerbation Per Year for Participants With ppFEV1 >75 at Baseline | Week 48 | Rate of protocol-defined pulmonary exacerbations reported through the Week 48/Early Termination visit will be annualized where a year is defined by 52 weeks and will be analyzed using a negative binomial regression. |
Countries
Belgium, Canada, France, Germany, Italy, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 100 mg CTX-4430 Once daily oral capsule for 48 weeks
CTX-4430 | 66 |
| 50 mg CTX-4430 Once daily oral capsule for 48 weeks
CTX-4430 | 67 |
| Matching Placebo Once daily oral capsule for 48 weeks
Placebo | 66 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Non-compliance with study drug | 1 | 2 | 4 |
| Overall Study | Physician Decision | 3 | 0 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 1 |
| Overall Study | Sponsor Request | 2 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 4 |
Baseline characteristics
| Characteristic | Total | 100 mg CTX-4430 | 50 mg CTX-4430 | Matching Placebo |
|---|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 2 Participants | 6 Participants | 4 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 187 Participants | 64 Participants | 61 Participants | 62 Participants |
| Age, Continuous | 23.7 years STANDARD_DEVIATION 3.43 | 24.3 years STANDARD_DEVIATION 3.24 | 23.7 years STANDARD_DEVIATION 3.64 | 23.2 years STANDARD_DEVIATION 3.38 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 5 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 192 Participants | 61 Participants | 65 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of Pulmonary Exacerbations in the year prior to Screening | 2.13 pulmonary Exacerbations/year STANDARD_DEVIATION 1.609 | 2.32 pulmonary Exacerbations/year STANDARD_DEVIATION 1.947 | 2.13 pulmonary Exacerbations/year STANDARD_DEVIATION 1.466 | 1.94 pulmonary Exacerbations/year STANDARD_DEVIATION 1.357 |
| On CFTR Modulator Therapy: No | 137 Participants | 45 Participants | 45 Participants | 47 Participants |
| On cystic fibrosis transmembrane conductance regulator (CFTR) Modulator Therapy: Yes | 62 Participants | 21 Participants | 22 Participants | 19 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 1 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 5 Participants | 3 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 190 Participants | 62 Participants | 62 Participants | 66 Participants |
| Sex: Female, Male Female | 101 Participants | 30 Participants | 38 Participants | 33 Participants |
| Sex: Female, Male Male | 98 Participants | 36 Participants | 29 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 67 | 0 / 66 |
| other Total, other adverse events | 66 / 66 | 67 / 67 | 65 / 66 |
| serious Total, serious adverse events | 27 / 66 | 26 / 67 | 21 / 66 |
Outcome results
Primary
Difference From Placebo in Absolute Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted (ppFEV1)
Difference from Placebo in absolute change from Baseline at Week 48 was assessed for FEV1 percent predicted.
Time frame: Baseline, Week 48
Population: Full Analysis Population - All subjects randomized to and receiving at least 1 dose of assigned treatment. The primary analysis was based upon the pooled results of the 100mg and 50mg doses.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 100 mg CTX-4430 | Difference From Placebo in Absolute Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted (ppFEV1) | -1.30 FEV1 percent predicted |
| 50 mg CTX-4430 | Difference From Placebo in Absolute Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted (ppFEV1) | -3.76 FEV1 percent predicted |
| Pooled CTX-4430 | Difference From Placebo in Absolute Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted (ppFEV1) | -2.53 FEV1 percent predicted |
| Matching Placebo | Difference From Placebo in Absolute Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted (ppFEV1) | -2.69 FEV1 percent predicted |
95% CI: [-1.34, 4.12]ANOVA
95% CI: [-3.78, 1.64]ANOVA
p-value: 0.4595% CI: [-2.2, 2.5]ANOVA
Secondary
Change From Baseline at 48 Weeks for Forced Vital Capacity Percent Predicted (FVC) and FEF25-75% (Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity) Percent Predicted
Time frame: Baseline, Week 48
Population: Full Analysis Population - All subjects randomized to and receiving at least 1 dose of assigned treatment. (Observed Data). The statistical analysis plans states the two active doses will be compared to placebo individually as well as pooled.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 100 mg CTX-4430 | Change From Baseline at 48 Weeks for Forced Vital Capacity Percent Predicted (FVC) and FEF25-75% (Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity) Percent Predicted | Forced vital capacity (FVC) percent predicted | -1.57 absolute change of percent predicted |
| 100 mg CTX-4430 | Change From Baseline at 48 Weeks for Forced Vital Capacity Percent Predicted (FVC) and FEF25-75% (Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity) Percent Predicted | Forced expiratory flow(FEF25-75%)percent predicted | -1.61 absolute change of percent predicted |
| 50 mg CTX-4430 | Change From Baseline at 48 Weeks for Forced Vital Capacity Percent Predicted (FVC) and FEF25-75% (Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity) Percent Predicted | Forced expiratory flow(FEF25-75%)percent predicted | -4.79 absolute change of percent predicted |
| 50 mg CTX-4430 | Change From Baseline at 48 Weeks for Forced Vital Capacity Percent Predicted (FVC) and FEF25-75% (Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity) Percent Predicted | Forced vital capacity (FVC) percent predicted | -2.06 absolute change of percent predicted |
| Pooled CTX-4430 | Change From Baseline at 48 Weeks for Forced Vital Capacity Percent Predicted (FVC) and FEF25-75% (Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity) Percent Predicted | Forced vital capacity (FVC) percent predicted | -1.82 absolute change of percent predicted |
| Pooled CTX-4430 | Change From Baseline at 48 Weeks for Forced Vital Capacity Percent Predicted (FVC) and FEF25-75% (Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity) Percent Predicted | Forced expiratory flow(FEF25-75%)percent predicted | -3.20 absolute change of percent predicted |
| Matching Placebo | Change From Baseline at 48 Weeks for Forced Vital Capacity Percent Predicted (FVC) and FEF25-75% (Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity) Percent Predicted | Forced vital capacity (FVC) percent predicted | -1.41 absolute change of percent predicted |
| Matching Placebo | Change From Baseline at 48 Weeks for Forced Vital Capacity Percent Predicted (FVC) and FEF25-75% (Forced Expiratory Flow During the Middle Half of the Forced Vital Capacity) Percent Predicted | Forced expiratory flow(FEF25-75%)percent predicted | -4.38 absolute change of percent predicted |
Secondary
Change From Baseline for C-reactive Protein (Hs-CRP)
Results were only calculated in subjects who had a verifiable result at the Baseline and Week 48 visits.
Time frame: Baseline, Week 48
Population: Full Analysis Population - All subjects randomized to and receiving at least 1 dose of assigned treatment and who had results at Baseline and Week 48. The statistical analysis plans states the two active doses will be compared to placebo individually as well as pooled.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 100 mg CTX-4430 | Change From Baseline for C-reactive Protein (Hs-CRP) | 2.16 mg/dL |
| 50 mg CTX-4430 | Change From Baseline for C-reactive Protein (Hs-CRP) | -0.33 mg/dL |
| Pooled CTX-4430 | Change From Baseline for C-reactive Protein (Hs-CRP) | 0.92 mg/dL |
| Matching Placebo | Change From Baseline for C-reactive Protein (Hs-CRP) | -1.87 mg/dL |
Secondary
Change From Baseline for Specified Biomarkers
Results were only calculated in subjects who had a verifiable result at the Baseline and Week 48 visits.
Time frame: Baseline, Week 48
Population: Full Analysis Population - All subjects randomized to and receiving at least 1 dose of assigned treatment and who had results at Baseline and Week 48. The statistical analysis plans states the two active doses will be compared to placebo individually as well as pooled.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 100 mg CTX-4430 | Change From Baseline for Specified Biomarkers | Sputum DNA | 0.06 log10(mcg/mL) |
| 100 mg CTX-4430 | Change From Baseline for Specified Biomarkers | Sputum Elastase | -0.02 log10(mcg/mL) |
| 50 mg CTX-4430 | Change From Baseline for Specified Biomarkers | Sputum Elastase | 0.17 log10(mcg/mL) |
| 50 mg CTX-4430 | Change From Baseline for Specified Biomarkers | Sputum DNA | 0.17 log10(mcg/mL) |
| Pooled CTX-4430 | Change From Baseline for Specified Biomarkers | Sputum DNA | 0.12 log10(mcg/mL) |
| Pooled CTX-4430 | Change From Baseline for Specified Biomarkers | Sputum Elastase | 0.08 log10(mcg/mL) |
| Matching Placebo | Change From Baseline for Specified Biomarkers | Sputum DNA | -0.05 log10(mcg/mL) |
| Matching Placebo | Change From Baseline for Specified Biomarkers | Sputum Elastase | -0.08 log10(mcg/mL) |
Secondary
Hazard Ratio Pulmonary Exacerbation While in the Study
Hazard Ratio of pulmonary exacerbation versus placebo for all subjects. Pulmonary exacerbations are defined as treatment with oral, inhaled, or intravenous antibiotic(s) for ≥4 of symptoms/signs per the modified Fuchs criteria.
Time frame: Week 48
Population: Full Analysis Population - All subjects randomized to and receiving at least 1 dose of assigned treatment. The statistical analysis plans states the two active doses will be compared to placebo individually as well as pooled.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg CTX-4430 | Hazard Ratio Pulmonary Exacerbation While in the Study | 0.88 hazard ratio |
| 50 mg CTX-4430 | Hazard Ratio Pulmonary Exacerbation While in the Study | 0.86 hazard ratio |
| Pooled CTX-4430 | Hazard Ratio Pulmonary Exacerbation While in the Study | 0.87 hazard ratio |
95% CI: [0.58, 1.34]Regression, Cox
95% CI: [0.56, 1.31]Regression, Cox
95% CI: [0.61, 1.25]Regression, Cox
Secondary
Number of Pulmonary Exacerbations Through 48 Weeks
Rate of protocol-defined pulmonary exacerbations reported through the Week 48/Early Termination visit will be annualized where a year is defined by 52 weeks and will be analyzed using a negative binomial regression.
Time frame: Week 48
Population: Full Analysis Population - All subjects randomized to and receiving at least 1 dose of assigned treatment. The statistical analysis plans states the two active doses will be compared to placebo individually as well as pooled.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 100 mg CTX-4430 | Number of Pulmonary Exacerbations Through 48 Weeks | 1.57 pulmonary exacerbations per year |
| 50 mg CTX-4430 | Number of Pulmonary Exacerbations Through 48 Weeks | 1.46 pulmonary exacerbations per year |
| Pooled CTX-4430 | Number of Pulmonary Exacerbations Through 48 Weeks | 1.51 pulmonary exacerbations per year |
| Matching Placebo | Number of Pulmonary Exacerbations Through 48 Weeks | 1.56 pulmonary exacerbations per year |
95% CI: [1.22, 2.02]
95% CI: [1.13, 1.89]
95% CI: [1.21, 2.01]
95% CI: [1.26, 1.81]
Secondary
Relative Change (Percent Change) From Baseline in ppFEV1
Percent change from Baseline for ppFEV1 at 48 weeks was assessed.
Time frame: Baseline, Week 48
Population: Full Analysis Population - All subjects randomized to and receiving at least 1 dose of assigned treatment. (Observed Data). The statistical analysis plans states the two active doses will be compared to placebo individually as well as pooled.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 100 mg CTX-4430 | Relative Change (Percent Change) From Baseline in ppFEV1 | -2.38 percent change from baseline |
| 50 mg CTX-4430 | Relative Change (Percent Change) From Baseline in ppFEV1 | -4.81 percent change from baseline |
| Pooled CTX-4430 | Relative Change (Percent Change) From Baseline in ppFEV1 | -3.60 percent change from baseline |
| Matching Placebo | Relative Change (Percent Change) From Baseline in ppFEV1 | -3.40 percent change from baseline |
Secondary
Subjects Without a Pulmonary Exacerbation While in the Study
Subjects who did not experience a protocol-defined pulmonary exacerbation during the study
Time frame: Week 48
Population: Full Analysis Population - All subjects randomized to and receiving at least 1 dose of assigned treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 100 mg CTX-4430 | Subjects Without a Pulmonary Exacerbation While in the Study | 25 Participants |
| 50 mg CTX-4430 | Subjects Without a Pulmonary Exacerbation While in the Study | 26 Participants |
| Pooled CTX-4430 | Subjects Without a Pulmonary Exacerbation While in the Study | 51 Participants |
| Matching Placebo | Subjects Without a Pulmonary Exacerbation While in the Study | 20 Participants |
Other Pre-specified
Hazard Ratio Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline
Hazard Ratio pulmonary exacerbation versus placebo for all subjects taking CFTR-modulating therapy at Baseline
Time frame: Week 48
Population: Population of subjects taking CFTR modulating therapy at Baseline. The statistical analysis plans states the two active doses will be compared to placebo individually as well as pooled.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg CTX-4430 | Hazard Ratio Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 0.73 hazard ratio |
| 50 mg CTX-4430 | Hazard Ratio Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 0.69 hazard ratio |
| Pooled CTX-4430 | Hazard Ratio Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 0.71 hazard ratio |
Other Pre-specified
Hazard Ratio Pulmonary Exacerbation for Participants With ppFEV1 >75 at Baseline
Hazard ratio of pulmonary exacerbation versus placebo for all subjects
Time frame: Week 48
Population: Population of subjects with Baseline ppFEV1 \>75. The statistical analysis plan states the two active doses will be compared to placebo individually as well as pooled.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 100 mg CTX-4430 | Hazard Ratio Pulmonary Exacerbation for Participants With ppFEV1 >75 at Baseline | 0.52 hazard ratio |
| 50 mg CTX-4430 | Hazard Ratio Pulmonary Exacerbation for Participants With ppFEV1 >75 at Baseline | 0.62 hazard ratio |
| Pooled CTX-4430 | Hazard Ratio Pulmonary Exacerbation for Participants With ppFEV1 >75 at Baseline | 0.57 hazard ratio |
95% CI: [0.25, 1.1]Regression, Cox
95% CI: [0.3, 1.27]Regression, Cox
95% CI: [0.31, 1.05]Regression, Cox
Post Hoc
Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48
Rate of protocol-defined pulmonary exacerbations reported through the Week 48/Early Termination visit will be annualized where a year is defined by 52 weeks and will be analyzed using a negative binomial regression.
Time frame: Week 48
Population: Subject's FEV1 percent predicted at screening are presented below.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| 100 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>50% | 1.5094 pulmonary exacerbations per year |
| 100 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>55% | 1.5006 pulmonary exacerbations per year |
| 100 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>60% | 1.2698 pulmonary exacerbations per year |
| 100 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>65% | 1.0473 pulmonary exacerbations per year |
| 100 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>70% | 0.9198 pulmonary exacerbations per year |
| 100 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>75% | 0.8417 pulmonary exacerbations per year |
| 50 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>75% | 1.2786 pulmonary exacerbations per year |
| 50 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>65% | 1.2523 pulmonary exacerbations per year |
| 50 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>50% | 1.4376 pulmonary exacerbations per year |
| 50 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>60% | 1.4446 pulmonary exacerbations per year |
| 50 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>55% | 1.4159 pulmonary exacerbations per year |
| 50 mg CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>70% | 1.1995 pulmonary exacerbations per year |
| Pooled CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>55% | 1.4576 pulmonary exacerbations per year |
| Pooled CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>60% | 1.3544 pulmonary exacerbations per year |
| Pooled CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>65% | 1.1452 pulmonary exacerbations per year |
| Pooled CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>75% | 1.0374 pulmonary exacerbations per year |
| Pooled CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>70% | 1.0504 pulmonary exacerbations per year |
| Pooled CTX-4430 | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>50% | 1.4731 pulmonary exacerbations per year |
| Matching Placebo | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>70% | 1.5365 pulmonary exacerbations per year |
| Matching Placebo | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>75% | 1.6125 pulmonary exacerbations per year |
| Matching Placebo | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>55% | 1.5425 pulmonary exacerbations per year |
| Matching Placebo | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>65% | 1.4489 pulmonary exacerbations per year |
| Matching Placebo | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>50% | 1.5297 pulmonary exacerbations per year |
| Matching Placebo | Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48 | Baseline FEV1>60% | 1.4728 pulmonary exacerbations per year |
Other Pre-specified
Number of Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline
Rate of protocol-defined pulmonary exacerbations reported through the Week 48/Early Termination visit will be annualized where a year is defined by 52 weeks and will be analyzed using a negative binomial regression.
Time frame: Week 48
Population: Population of subjects taking CFTR modulating therapy at Baseline. The statistical analysis plans states the two active doses will be compared to placebo individually as well as pooled.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 100 mg CTX-4430 | Number of Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 1.24 pulmonary exacerbations per year |
| 50 mg CTX-4430 | Number of Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 1.08 pulmonary exacerbations per year |
| Pooled CTX-4430 | Number of Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 1.16 pulmonary exacerbations per year |
| Matching Placebo | Number of Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 1.45 pulmonary exacerbations per year |
Other Pre-specified
Number of Pulmonary Exacerbation Per Year for Participants With ppFEV1 >75 at Baseline
Rate of protocol-defined pulmonary exacerbations reported through the Week 48/Early Termination visit will be annualized where a year is defined by 52 weeks and will be analyzed using a negative binomial regression.
Time frame: Week 48
Population: Population of subjects with Baseline ppFEV1 \>75. The statistical analysis plans states the two active doses will be compared to placebo individually as well as combined. The statistical analysis plans states the two active doses will be compared to placebo individually as well as pooled.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 100 mg CTX-4430 | Number of Pulmonary Exacerbation Per Year for Participants With ppFEV1 >75 at Baseline | 0.84 pulmonary exacerbations per year |
| 50 mg CTX-4430 | Number of Pulmonary Exacerbation Per Year for Participants With ppFEV1 >75 at Baseline | 1.28 pulmonary exacerbations per year |
| Pooled CTX-4430 | Number of Pulmonary Exacerbation Per Year for Participants With ppFEV1 >75 at Baseline | 1.04 pulmonary exacerbations per year |
| Matching Placebo | Number of Pulmonary Exacerbation Per Year for Participants With ppFEV1 >75 at Baseline | 1.61 pulmonary exacerbations per year |
95% CI: [0.49, 1.44]
95% CI: [0.84, 1.96]
95% CI: [1.07, 2.42]
95% CI: [0.74, 1.46]
Other Pre-specified
Subjects Without a Pulmonary Exacerbation by Participants With ppFEV1 >75 at Baseline
Subjects who did not experience a protocol-defined pulmonary exacerbation during the study.
Time frame: Week 48
Population: Population of subjects with Baseline ppFEV1 \>75.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 100 mg CTX-4430 | Subjects Without a Pulmonary Exacerbation by Participants With ppFEV1 >75 at Baseline | 11 Participants |
| 50 mg CTX-4430 | Subjects Without a Pulmonary Exacerbation by Participants With ppFEV1 >75 at Baseline | 12 Participants |
| Pooled CTX-4430 | Subjects Without a Pulmonary Exacerbation by Participants With ppFEV1 >75 at Baseline | 23 Participants |
| Matching Placebo | Subjects Without a Pulmonary Exacerbation by Participants With ppFEV1 >75 at Baseline | 6 Participants |
Other Pre-specified
Subjects Without a Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline
Subjects who did not experience a protocol-defined pulmonary exacerbation during the study.
Time frame: Week 48
Population: Population of subjects taking CFTR modulating therapy at Baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 100 mg CTX-4430 | Subjects Without a Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 10 Participants |
| 50 mg CTX-4430 | Subjects Without a Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 10 Participants |
| Pooled CTX-4430 | Subjects Without a Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 20 Participants |
| Matching Placebo | Subjects Without a Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline | 6 Participants |