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

Study Overview
=================
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).

Official Title
-----------------
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy, Safety, and Tolerability of CTX-4430 Administered Orally Once-Daily for 48 Weeks in Adult Patients With Cystic Fibrosis

Conditions
-----------------
Cystic Fibrosis

Intervention / Treatment
-----------------
* Drug: CTX-4430
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg CTX-4430<br>Once daily oral capsule for 48 weeks | Drug: CTX-4430<br> <br> |
| Experimental: 100 mg CTX-4430<br>Once daily oral capsule for 48 weeks | Drug: CTX-4430<br> <br> |
| Placebo Comparator: Matching Placebo<br>Once daily oral capsule for 48 weeks | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Week 48 | 
| 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. | Week 48 | 
| Subjects Without a Pulmonary Exacerbation While in the Study | Subjects who did not experience a protocol-defined pulmonary exacerbation during the study | Week 48 | 
| Relative Change (Percent Change) From Baseline in ppFEV1 | Percent change from Baseline for ppFEV1 at 48 weeks was assessed. | Baseline, Week 48 | 
| 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 | Results were only calculated in subjects who had a verifiable result at the Baseline and Week 48 visits. | Baseline, Week 48 | 
| 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. | Baseline, Week 48 |