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Trial record 2 of 2 for:    CTX-4430 | Cystic Fibrosis

EMPIRE CF: A Phase 2 Study to Evaluate the Efficacy, Safety, and Tolerability of CTX-4430 in Adult Cystic Fibrosis (CF) Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02443688
Recruitment Status : Completed
First Posted : May 14, 2015
Results First Posted : July 25, 2019
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Celtaxsys, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Cystic Fibrosis
Interventions Drug: CTX-4430
Drug: Placebo
Enrollment 200
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 100 mg CTX-4430 50 mg CTX-4430 Matching Placebo
Hide Arm/Group Description

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

Placebo

Period Title: Overall Study
Started 66 67 67
Completed 54 58 55
Not Completed 12 9 12
Reason Not Completed
Adverse Event             2             3             2
Lost to Follow-up             1             0             0
Physician Decision             3             0             1
Pregnancy             0             0             1
Withdrawal by Subject             3             3             4
Non-compliance with study drug             1             2             4
Sponsor Request             2             1             0
Arm/Group Title 100 mg CTX-4430 50 mg CTX-4430 Matching Placebo Total
Hide Arm/Group Description

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

Placebo

Total of all reporting groups
Overall Number of Baseline Participants 66 67 66 199
Hide Baseline Analysis Population Description
One subject in the matching placebo cohort was randomized but did not take any study drug. Therefore, the matching placebo group has 66 subjects listed instead of 67 subjects making it a total of 199 subjects who received study drug.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 67 participants 66 participants 199 participants
<=18 years
2
   3.0%
6
   9.0%
4
   6.1%
12
   6.0%
Between 18 and 65 years
64
  97.0%
61
  91.0%
62
  93.9%
187
  94.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 66 participants 67 participants 66 participants 199 participants
24.3  (3.24) 23.7  (3.64) 23.2  (3.38) 23.7  (3.43)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 67 participants 66 participants 199 participants
Female
30
  45.5%
38
  56.7%
33
  50.0%
101
  50.8%
Male
36
  54.5%
29
  43.3%
33
  50.0%
98
  49.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 67 participants 66 participants 199 participants
Hispanic or Latino
5
   7.6%
2
   3.0%
0
   0.0%
7
   3.5%
Not Hispanic or Latino
61
  92.4%
65
  97.0%
66
 100.0%
192
  96.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 67 participants 66 participants 199 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   1.5%
3
   4.5%
0
   0.0%
4
   2.0%
White
62
  93.9%
62
  92.5%
66
 100.0%
190
  95.5%
More than one race
3
   4.5%
2
   3.0%
0
   0.0%
5
   2.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
On cystic fibrosis transmembrane conductance regulator (CFTR) Modulator Therapy: Yes  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 67 participants 66 participants 199 participants
21
  31.8%
22
  32.8%
19
  28.8%
62
  31.2%
On CFTR Modulator Therapy: No  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 66 participants 67 participants 66 participants 199 participants
45
  68.2%
45
  67.2%
47
  71.2%
137
  68.8%
Number of Pulmonary Exacerbations in the year prior to Screening  
Mean (Standard Deviation)
Unit of measure:  Pulmonary Exacerbations/year
Number Analyzed 66 participants 67 participants 66 participants 199 participants
2.32  (1.947) 2.13  (1.466) 1.94  (1.357) 2.13  (1.609)
1.Primary Outcome
Title Difference From Placebo in Absolute Change From Baseline in Forced Expiratory Volume in 1 Second Percent Predicted (ppFEV1)
Hide Description Difference from Placebo in absolute change from Baseline at Week 48 was assessed for FEV1 percent predicted.
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

The average of the Week 48 absolute change from Baseline in FEV1 percent predicted for the two CTX-4430 doses.
Once daily oral capsule for 48 weeks
Overall Number of Participants Analyzed 66 67 133 66
Mean (95% Confidence Interval)
Unit of Measure: FEV1 percent predicted
-1.30
(-3.22 to 0.62)
-3.76
(-5.65 to -1.86)
-2.53
(-3.88 to -1.18)
-2.69
(-4.63 to -0.75)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 100 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments Single Group Difference from Placebo Mean Change from Baseline with 95% confidence interval (CI)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.39
Confidence Interval (2-Sided) 95%
-1.34 to 4.12
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 50 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments Single Group Difference from Placebo Mean Change from Baseline with 95% CI
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.07
Confidence Interval (2-Sided) 95%
-3.78 to 1.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Pooled CTX-4430
Comments [Not Specified]
Type of Statistical Test Superiority
Comments Difference from placebo of pooled arms (100mg CTX-4430 and 50mg CTX-4430) in change from baseline in ppFEV1 at Week 48.
Statistical Test of Hypothesis P-Value 0.45
Comments 0.1 alpha level (2-sided) prespecified
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-2.20 to 2.50
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.2
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Pulmonary Exacerbations Through 48 Weeks
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 66 67 133 66
Mean (95% Confidence Interval)
Unit of Measure: pulmonary exacerbations per year
1.57
(1.22 to 2.02)
1.46
(1.13 to 1.89)
1.51
(1.26 to 1.81)
1.56
(1.21 to 2.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 100 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments Single Group Rate with 95% CI
Method of Estimation Estimation Parameter see Estimation Comment below
Estimated Value 1.57
Confidence Interval (2-Sided) 95%
1.22 to 2.02
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.20
Estimation Comments Estimated using negative binomial distribution by treatment group unadjusted for multiple comparisons.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 50 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments Single Group Rate with 95% CI
Method of Estimation Estimation Parameter see Estimation Comment below
Estimated Value 1.46
Confidence Interval (2-Sided) 95%
1.13 to 1.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.19
Estimation Comments Estimated using negative binomial distribution by treatment group unadjusted for multiple comparisons.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Matching Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Single Group Rate with 95% CI
Method of Estimation Estimation Parameter see Estimation Comment below
Estimated Value 1.56
Confidence Interval (2-Sided) 95%
1.21 to 2.01
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.20
Estimation Comments Estimated using negative binomial distribution by treatment group unadjusted for multiple comparisons.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments Pooled Group Rate with 95% CI
Method of Estimation Estimation Parameter see Estimation Comment below
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
1.26 to 1.81
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.14
Estimation Comments Estimated using negative binomial distribution unadjusted for multiple comparisons.
3.Secondary Outcome
Title Hazard Ratio Pulmonary Exacerbation While in the Study
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results
Overall Number of Participants Analyzed 66 67 133
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: hazard ratio
0.88
(0.576 to 1.339)
0.86
(0.563 to 1.308)
0.87
(0.605 to 1.246)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 100 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments 95% 2-sided confidence interval for the Hazard Ratio relative to Placebo unadjusted for multiple comparisons
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.88
Confidence Interval (2-Sided) 95%
0.58 to 1.34
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 50 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments 95% 2-sided confidence interval for the Hazard Ratio relative to Placebo unadjusted for multiple comparisons
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.56 to 1.31
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 100 mg CTX-4430, 50 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments 95% 2-sided confidence interval for the Hazard Ratio Relative to Placebo unadjusted for multiple comparisons
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.61 to 1.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.16
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Subjects Without a Pulmonary Exacerbation While in the Study
Hide Description Subjects who did not experience a protocol-defined pulmonary exacerbation during the study
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population - All subjects randomized to and receiving at least 1 dose of assigned treatment.
Arm/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 66 67 133 66
Measure Type: Count of Participants
Unit of Measure: Participants
25
  37.9%
26
  38.8%
51
  38.3%
20
  30.3%
5.Secondary Outcome
Title Relative Change (Percent Change) From Baseline in ppFEV1
Hide Description Percent change from Baseline for ppFEV1 at 48 weeks was assessed.
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 59 59 118 57
Mean (95% Confidence Interval)
Unit of Measure: percent change from baseline
-2.38
(-5.37 to 0.60)
-4.81
(-7.84 to -1.79)
-3.60
(-5.72 to -1.47)
-3.40
(-6.59 to -0.22)
6.Secondary Outcome
Title 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
Hide Description [Not Specified]
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 59 59 118 57
Mean (95% Confidence Interval)
Unit of Measure: absolute change of percent predicted
Forced vital capacity (FVC) percent predicted
-1.57
(-3.37 to 0.23)
-2.06
(-3.88 to -0.25)
-1.82
(-3.10 to -0.54)
-1.41
(-3.32 to 0.51)
Forced expiratory flow(FEF25-75%)percent predicted
-1.61
(-4.26 to 1.03)
-4.79
(-7.46 to -2.11)
-3.20
(-5.08 to -1.32)
-4.38
(-7.20 to -1.57)
7.Secondary Outcome
Title Change From Baseline for Specified Biomarkers
Hide Description Results were only calculated in subjects who had a verifiable result at the Baseline and Week 48 visits.
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 66 67 133 66
Mean (95% Confidence Interval)
Unit of Measure: log10(mcg/mL)
Sputum DNA Number Analyzed 33 participants 42 participants 75 participants 42 participants
0.06
(-0.13 to 0.25)
0.17
(0.01 to 0.34)
0.12
(-0.01 to 0.24)
-0.05
(-0.22 to 0.12)
Sputum Elastase Number Analyzed 33 participants 43 participants 76 participants 41 participants
-0.02
(-0.20 to 0.16)
0.17
(0.02 to 0.33)
0.08
(-0.04 to 0.20)
-0.08
(-0.25 to 0.08)
8.Secondary Outcome
Title Change From Baseline for C-reactive Protein (Hs-CRP)
Hide Description Results were only calculated in subjects who had a verifiable result at the Baseline and Week 48 visits.
Time Frame Baseline, Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 51 55 106 51
Mean (95% Confidence Interval)
Unit of Measure: mg/dL
2.16
(-1.84 to 6.16)
-0.33
(-4.21 to 3.56)
0.92
(-1.87 to 3.70)
-1.87
(-5.91 to 2.17)
9.Other Pre-specified Outcome
Title Number of Pulmonary Exacerbation Per Year for Participants With ppFEV1 >75 at Baseline
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 22 25 47 24
Mean (95% Confidence Interval)
Unit of Measure: pulmonary exacerbations per year
0.84
(0.49 to 1.44)
1.28
(0.84 to 1.96)
1.04
(0.74 to 1.46)
1.61
(1.07 to 2.42)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 100 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments Single Group Rate with 95% CI
Method of Estimation Estimation Parameter see Estimation Comment below
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.49 to 1.44
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.23
Estimation Comments Estimated using negative binomial distribution by treatment group unadjusted for multiple comparisons.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 50 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments Single Group Rate with 95% CI
Method of Estimation Estimation Parameter see Estimation Comment below
Estimated Value 1.28
Confidence Interval (2-Sided) 95%
0.84 to 1.96
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.28
Estimation Comments Estimated using negative binomial distribution by treatment group unadjusted for multiple comparisons.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Matching Placebo
Comments [Not Specified]
Type of Statistical Test Other
Comments Single Group Rate with 95% CI
Method of Estimation Estimation Parameter see Estimation Comment below
Estimated Value 1.61
Confidence Interval (2-Sided) 95%
1.07 to 2.42
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.34
Estimation Comments Estimated using negative binomial distribution by treatment group unadjusted for multiple comparisons.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Pooled CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments Group Rate with 95% CI
Method of Estimation Estimation Parameter see Estimation Comment below
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.74 to 1.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.18
Estimation Comments Estimated using negative binomial distribution by treatment group unadjusted for multiple comparisons.
10.Other Pre-specified Outcome
Title Hazard Ratio Pulmonary Exacerbation for Participants With ppFEV1 >75 at Baseline
Hide Description Hazard ratio of pulmonary exacerbation versus placebo for all subjects
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results.
Overall Number of Participants Analyzed 22 25 47
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: hazard ratio
0.52
(0.245 to 1.101)
0.62
(0.304 to 1.274)
0.57
(0.307 to 1.051)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 100 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments 95% 2-sided confidence interval for the Hazard Ratio Relative to Placebo unadjusted for multiple comparisons
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.25 to 1.10
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 50 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments 95% 2-sided confidence interval for the Hazard Ratio Relative to Placebo unadjusted for multiple comparisons
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.30 to 1.27
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 100 mg CTX-4430, 50 mg CTX-4430
Comments [Not Specified]
Type of Statistical Test Other
Comments 95% 2-sided confidence interval for the Hazard Ratio Relative to Placebo unadjusted for multiple comparisons
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.31 to 1.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.18
Estimation Comments [Not Specified]
11.Other Pre-specified Outcome
Title Subjects Without a Pulmonary Exacerbation by Participants With ppFEV1 >75 at Baseline
Hide Description Subjects who did not experience a protocol-defined pulmonary exacerbation during the study.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Population of subjects with Baseline ppFEV1 >75.
Arm/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results.

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 22 25 47 24
Measure Type: Count of Participants
Unit of Measure: Participants
11
  50.0%
12
  48.0%
23
  48.9%
6
  25.0%
12.Other Pre-specified Outcome
Title Number of Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results.

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 21 22 43 19
Mean (95% Confidence Interval)
Unit of Measure: pulmonary exacerbations per year
1.24
(0.78 to 1.96)
1.08
(0.67 to 1.74)
1.16
(0.83 to 1.61)
1.45
(0.91 to 2.31)
13.Other Pre-specified Outcome
Title Hazard Ratio Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline
Hide Description Hazard Ratio pulmonary exacerbation versus placebo for all subjects taking CFTR-modulating therapy at Baseline
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results
Overall Number of Participants Analyzed 21 22 43
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: hazard ratio
0.73
(0.328 to 1.641)
0.69
(0.313 to 1.514)
0.71
(0.359 to 1.408)
14.Other Pre-specified Outcome
Title Subjects Without a Pulmonary Exacerbation by Subjects if Taking CFTR-Modulator Therapy at Baseline
Hide Description Subjects who did not experience a protocol-defined pulmonary exacerbation during the study.
Time Frame Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Population of subjects taking CFTR modulating therapy at Baseline.
Arm/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 21 22 43 19
Measure Type: Count of Participants
Unit of Measure: Participants
10
  47.6%
10
  45.5%
20
  46.5%
6
  31.6%
15.Post-Hoc Outcome
Title Number of Pulmonary Exacerbation by Baseline FEV1 Percent Predicted at Week 48
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Subject's FEV1 percent predicted at screening are presented below.
Arm/Group Title 100 mg CTX-4430 50 mg CTX-4430 Pooled CTX-4430 Matching Placebo
Hide Arm/Group Description:

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral 100mg and 50mg pooled results

Once daily oral capsule for 48 weeks

Placebo

Overall Number of Participants Analyzed 66 67 133 66
Mean (95% Confidence Interval)
Unit of Measure: pulmonary exacerbations per year
Baseline FEV1>50% Number Analyzed 62 participants 65 participants 127 participants 63 participants
1.5094
(1.1549 to 1.9727)
1.4376
(1.0991 to 1.8803)
1.4731
(1.2187 to 1.7806)
1.5297
(1.1708 to 1.9986)
Baseline FEV1>55% Number Analyzed 53 participants 60 participants 113 participants 55 participants
1.5006
(1.1265 to 1.9989)
1.4159
(1.0760 to 1.8633)
1.4576
(1.1952 to 1.7777)
1.5425
(1.1643 to 2.0435)
Baseline FEV1>60% Number Analyzed 43 participants 52 participants 95 participants 43 participants
1.2698
(0.9181 to 1.7561)
1.4446
(1.0907 to 1.9133)
1.3544
(1.0928 to 1.6785)
1.4728
(1.0795 to 2.0094)
Baseline FEV1>65% Number Analyzed 35 participants 40 participants 75 participants 39 participants
1.0473
(0.7170 to 1.5298)
1.2523
(0.9018 to 1.7390)
1.1452
(0.8912 to 1.4716)
1.4489
(1.0540 to 1.9918)
Baseline FEV1>70% Number Analyzed 29 participants 31 participants 60 participants 32 participants
0.9198
(0.5930 to 1.4269)
1.1995
(0.8250 to 1.7440)
1.0504
(0.7871 to 1.4018)
1.5365
(1.0912 to 2.1636)
Baseline FEV1>75% Number Analyzed 22 participants 25 participants 47 participants 24 participants
0.8417
(0.4913 to 1.4418)
1.2786
(0.8358 to 1.9560)
1.0374
(0.7361 to 1.4619)
1.6125
(1.0728 to 2.4237)
Time Frame Baseline up to 28 days after the subject's last dose of study medication where the last dose is 48 weeks or early discontinuation of study drug.
Adverse Event Reporting Description An adverse event (AE) is any untoward medical occurrence in a subject administered a pharmaceutical product and does not necessarily have a causal relationship with this product. For purposes of this trial, AEs will be reported from the signing of the study informed consent (ICF) through study completion or early termination. A Treatment-Emergent AE is an AE that occurs after the first dose of study medication.
 
Arm/Group Title 100 mg CTX-4430 50 mg CTX-4430 Matching Placebo
Hide Arm/Group Description

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

CTX-4430

Once daily oral capsule for 48 weeks

Placebo

All-Cause Mortality
100 mg CTX-4430 50 mg CTX-4430 Matching Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/66 (0.00%)   0/67 (0.00%)   0/66 (0.00%) 
Hide Serious Adverse Events
100 mg CTX-4430 50 mg CTX-4430 Matching Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   27/66 (40.91%)   26/67 (38.81%)   21/66 (31.82%) 
Blood and lymphatic system disorders       
Haemolytic Anaemia * 1  0/66 (0.00%)  0/67 (0.00%)  1/66 (1.52%) 
Gastrointestinal disorders       
Distal intestinal obstruction syndrome * 1  1/66 (1.52%)  1/67 (1.49%)  0/66 (0.00%) 
Vomiting * 1  0/66 (0.00%)  1/67 (1.49%)  0/66 (0.00%) 
Infections and infestations       
Appendicitis * 1  1/66 (1.52%)  0/67 (0.00%)  0/66 (0.00%) 
Cellulitis * 1  1/66 (1.52%)  0/67 (0.00%)  0/66 (0.00%) 
Chronic Sinusitis * 1  0/66 (0.00%)  1/67 (1.49%)  0/66 (0.00%) 
Infective pulmonary exacerbation of cystic fibrosis * 1  21/66 (31.82%)  23/67 (34.33%)  19/66 (28.79%) 
Lower respiratory tract infection fungal * 1  1/66 (1.52%)  0/67 (0.00%)  0/66 (0.00%) 
Nocardiosis * 1  0/66 (0.00%)  0/67 (0.00%)  1/66 (1.52%) 
Pneumonia mycoplasmal * 1  0/66 (0.00%)  1/67 (1.49%)  0/66 (0.00%) 
Pyelonephritis * 1  0/66 (0.00%)  1/67 (1.49%)  0/66 (0.00%) 
Rhinovirus infection * 1  0/66 (0.00%)  0/67 (0.00%)  1/66 (1.52%) 
Scedosporium infection * 1  0/66 (0.00%)  0/67 (0.00%)  1/66 (1.52%) 
Sepsis * 1  1/66 (1.52%)  0/67 (0.00%)  0/66 (0.00%) 
Sinusitis * 1  1/66 (1.52%)  0/67 (0.00%)  0/66 (0.00%) 
Injury, poisoning and procedural complications       
Lower limb fracture * 1  0/66 (0.00%)  1/67 (1.49%)  0/66 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Borderline serous tumour of ovary * 1  0/66 (0.00%)  1/67 (1.49%)  0/66 (0.00%) 
Renal and urinary disorders       
Calculus ureteric * 1  0/66 (0.00%)  0/67 (0.00%)  1/66 (1.52%) 
Respiratory, thoracic and mediastinal disorders       
Acute Respiratory Failure * 1  0/66 (0.00%)  1/67 (1.49%)  0/66 (0.00%) 
Cough * 1  0/66 (0.00%)  0/67 (0.00%)  1/66 (1.52%) 
Haemoptysis * 1  1/66 (1.52%)  1/67 (1.49%)  2/66 (3.03%) 
Nasal septum deviation * 1  1/66 (1.52%)  0/67 (0.00%)  0/66 (0.00%) 
Surgical and medical procedures       
Antibiotic therapy * 1  2/66 (3.03%)  0/67 (0.00%)  0/66 (0.00%) 
Therapeutic embolisation * 1  0/66 (0.00%)  0/67 (0.00%)  1/66 (1.52%) 
Therapy Change * 1  1/66 (1.52%)  0/67 (0.00%)  0/66 (0.00%) 
1
Term from vocabulary, MedDRA (18.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
100 mg CTX-4430 50 mg CTX-4430 Matching Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   66/66 (100.00%)   67/67 (100.00%)   65/66 (98.48%) 
Gastrointestinal disorders       
Diarrhoea * 1  5/66 (7.58%)  9/67 (13.43%)  4/66 (6.06%) 
Nausea * 1  8/66 (12.12%)  5/67 (7.46%)  5/66 (7.58%) 
Abdominal pain upper * 1  3/66 (4.55%)  7/67 (10.45%)  5/66 (7.58%) 
Vomiting * 1  3/66 (4.55%)  1/67 (1.49%)  4/66 (6.06%) 
Abdominal pain * 1  4/66 (6.06%)  3/67 (4.48%)  4/66 (6.06%) 
Constipation * 1  1/66 (1.52%)  4/67 (5.97%)  3/66 (4.55%) 
General disorders       
Fatigue * 1  9/66 (13.64%)  9/67 (13.43%)  7/66 (10.61%) 
Pyrexia * 1  8/66 (12.12%)  6/67 (8.96%)  7/66 (10.61%) 
Chest discomfort * 1  8/66 (12.12%)  3/67 (4.48%)  7/66 (10.61%) 
Infections and infestations       
Infective pulmonary exacerbation of cystic fibrosis * 1  43/66 (65.15%)  45/67 (67.16%)  49/66 (74.24%) 
Nasopharyngitis * 1  14/66 (21.21%)  11/67 (16.42%)  13/66 (19.70%) 
Sinusitis * 1  6/66 (9.09%)  3/67 (4.48%)  5/66 (7.58%) 
Gastroenteritis * 1  4/66 (6.06%)  1/67 (1.49%)  2/66 (3.03%) 
Influenza * 1  5/66 (7.58%)  3/67 (4.48%)  4/66 (6.06%) 
Rhinitis * 1  3/66 (4.55%)  4/67 (5.97%)  2/66 (3.03%) 
Upper respiratory tract infection * 1  4/66 (6.06%)  4/67 (5.97%)  5/66 (7.58%) 
Investigations       
Alanine aminotransferase increased * 1  4/66 (6.06%)  0/67 (0.00%)  2/66 (3.03%) 
Forced expiratory volume decreased * 1  5/66 (7.58%)  4/67 (5.97%)  4/66 (6.06%) 
Sputum Abnormal * 1  0/66 (0.00%)  4/67 (5.97%)  1/66 (1.52%) 
Weight decreased * 1  1/66 (1.52%)  4/67 (5.97%)  4/66 (6.06%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  5/66 (7.58%)  3/67 (4.48%)  1/66 (1.52%) 
Back pain * 1  1/66 (1.52%)  4/67 (5.97%)  1/66 (1.52%) 
Nervous system disorders       
Headache * 1  9/66 (13.64%)  16/67 (23.88%)  7/66 (10.61%) 
Respiratory, thoracic and mediastinal disorders       
Cough * 1  29/66 (43.94%)  27/67 (40.30%)  21/66 (31.82%) 
Haemoptysis * 1  12/66 (18.18%)  17/67 (25.37%)  11/66 (16.67%) 
Sputum increased * 1  7/66 (10.61%)  13/67 (19.40%)  11/66 (16.67%) 
Oropharyngeal pain * 1  9/66 (13.64%)  7/67 (10.45%)  4/66 (6.06%) 
Nasal congestion * 1  8/66 (12.12%)  7/67 (10.45%)  9/66 (13.64%) 
Dyspnoea * 1  5/66 (7.58%)  6/67 (8.96%)  5/66 (7.58%) 
Epistaxis * 1  3/66 (4.55%)  4/67 (5.97%)  1/66 (1.52%) 
Paranasal sinus hypersecretion * 1  0/66 (0.00%)  5/67 (7.46%)  1/66 (1.52%) 
Rales * 1  4/66 (6.06%)  1/67 (1.49%)  1/66 (1.52%) 
Rhinorrhoea * 1  5/66 (7.58%)  6/67 (8.96%)  2/66 (3.03%) 
Sinus congestion * 1  2/66 (3.03%)  5/67 (7.46%)  5/66 (7.58%) 
Skin and subcutaneous tissue disorders       
Rash * 1  6/66 (9.09%)  3/67 (4.48%)  1/66 (1.52%) 
1
Term from vocabulary, MedDRA (18.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

PI is free to publish results of the study after (1) the first multi-center publication or (2) 24 months after close of the study, whichever occurs first.

Proposed publications are to be submitted to the sponsor for review and comment for a period of at least 90 days (which may be extended under certain circumstances related to protection of intellectual property as well as for deletion of any Confidential Information).

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Clincal Operations
Organization: Celtaxsys, Inc.
Phone: 4702060153 ext 123
EMail: sbirnbaum@celtaxsys.com
Layout table for additonal information
Responsible Party: Celtaxsys, Inc.
ClinicalTrials.gov Identifier: NCT02443688    
Other Study ID Numbers: CTX-4430-CF-201
First Submitted: May 8, 2015
First Posted: May 14, 2015
Results First Submitted: April 29, 2019
Results First Posted: July 25, 2019
Last Update Posted: September 4, 2019