Cystic Fibrosis MedDRA version: 20.0 Level: PT Classification code 10011763 Term: Cystic fibrosis lung System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: PT Classification code 10011762 Term: Cystic fibrosis System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: CTX-4430
Product Code: CTX-4430
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: acebilustat
CAS Number: 943764-99-
Sponsors
Celtaxsys Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients are eligible to participate in the study if they meet all of the following inclusion criteria: 1. 18 to 30 years of age inclusive at the time of Screening 2. Documented, confirmed diagnosis of pulmonary CF (defined as follows): • CF signs and symptoms AND • Either 2 CFTR mutations on genetic testing OR sweat chloride =60 mEq/L 3. Medically stable, in the Investigator’s opinion 4. At least 1 pulmonary exacerbation, based on the Investigator’s judgment, in the 12 months before Screening 5. Resolution of any pulmonary exacerbation of CF at least 14 days before Screening, in the Investigator’s opinion 6. On a stable regimen of CF treatments with no change for at least 14 days before Screening and between Screening and Baseline 7. If on ivacaftor or ivacaftor-lumacaftor combination, on a stable regimen for at least 8 weeks before Baseline 8. No clinical or radiological evidence, per the Investigator’s site procedures, of clinically significant lung abnormalities (e.g., major atelectasis, pneumothorax) 9. FEV1 =50 percent predicted at Screening 10. Resting oxygen saturation >92% on room air 11. Body mass index (BMI) =17.0 kg/m2 12. No smoking (including electronic cigarettes) for at least 6 months before Screening and agreement not to use such products for the duration of the study 13. Females of childbearing potential must have a negative pregnancy test at Screening (unless surgically sterile) and must agree to use an effective contraception method from screening throughout the duration of the study 14. Able to perform spirometry according to European Respiratory Society/American Thoracic Society guidance 15. Able to swallow investigational product (IP) whole 16. Able to comply with the study procedures, in the opinion of the Investigator 17. Has provided informed consent to participate in the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 195 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Patients are eligible to participate in this study if they meet none of the following exclusion criteria: 1. In the opinion of the Investigator, any significant clinical/laboratory/radiological/spirometric sign of unstable or unexpectedly deteriorating respiratory disease within 14 days before Screening or between Screening and Baseline (These clinical/laboratory/radiological/ spirometric signs include, but are not limited to, features suggestive of a pulmonary exacerbation as suggested by the modified Fuchs’ criteria.) 2. A medical condition that is unstable, could be adversely impacted by participation in the study, or could impact assessment of the study results, in the opinion of the Investigator 3. History of organ transplantation 4. History of either alcoholism or drug abuse in the opinion of the investigator 5. Clinically significant hemoptysis (e.g., > approximately 30 cc per episode, or clinically significant in the Investigator’s opinion) within 180 days before Screening 6. Colonization with organisms associated with a more rapid decline in respiratory function in CF patients (e.g. all Burkholderia species, Mycobacterium abscessus). Subjects with a history of a positive culture could be considered free of colonization if she/he has had 6 subsequent respiratory tract cultures negative for these bacteria within the past 24 months prior to Screening, with one of these cultures obtained within 6 months prior to Screening 7. Active allergic bronchopulmonary aspergillosis at Screening or at Baseline 8. Any clinically significant ECG abnormality, in the Investigator’s opinion 9. Positive serology for HIV-1 or HIV-2 antibody, hepatitis C virus antibody, or hepatitis B surface antigen at Screening 10. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =2x the upper limit of normal (ULN) at Screening 11. Bilirubin >1.25 x ULN at Screening. Subjects with known Gilbert’s syndrome can be included with bilirubin >1.25 x ULN 12. Any subject with cirrhosis of the liver 13. Any subject with portal hypertension 14. Neutrophil count 3 times per week) of a high-dose NSAID (e.g., >1.6 g ibuprofen/day) within 60 days before Screening or between Screening and Baseline 19. Participation in a clinical trial for any medical/device product within 30 days before Screening (participation in a noninterventional or observational study is permitted) 20. Pregnant or nursing women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Efficacy: Analysis of change from Baseline to Week 48 in FEV1 percent predicted Safety: AE recording ; Timepoint(s) of evaluation of this end point: Safety, AE recording: screening, baseline and at weeks 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52. Efficacy, spirometry: screening, baseline and at weeks 4, 8, 12, 16, 24, 32, 40, 48, 52. ; Main Objective: - To evaluate the safety and tolerability of CTX-4430 administered orally once-daily to cystic fibrosis (CF) patients for 48 weeks - To evaluate the efficacy of CTX-4430 administered orally once-daily to CF patients for 48 weeks as determined by the absolute change from Baseline in FEV1 (forced expiratory volume in 1 second) percent predicted ; Secondary Objective: 1. Efficacy evaluation of CTX-4430 as determined by the relative change from Baseline in FEV1 percent predicted 2. Evaluation of the effect of orally administered CTX-4430 on FVC % predicted and FEF25-75% predicted 3. Evaluation of the effect of orally administered CTX-4430 on time to first pulmonary exacerbation while in the study 3.1 Evaluation of the effect of orally administered CTX-4430 on the number of pulmonary exacerbations 3.2 Evaluation of the effect of orally administered CTX-4430 on specified biomarkers (sputum DNA and elastase and serum hs-CRP) Exploratory Objectives: - Effect evaluation of orally administered CTX-4430 on sputum bacterial density - Population PK of orally administered CTX-4430 after first dose and at steady state - Change from Baseline evaluation in subject’s health-related QOL while on CTX-4430 administered orally 1x daily for 48 w | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): CLINICAL ENDPOINTS - spirometry-based secondary endpoints will be analyzed using the same methods as the primary endpoint. For time points prior to 48 weeks, only descriptive statistics will be presented. - Pulmonary exacerbations: time to first pulmonary exacerbation and number of pulmonary exacerbations. BIOMARKER ENDPOINTS - sputum DNA and elastase, serum hs-CRP EXPLORATORY ENDPOINTS - pharmacokinetics - sputum bacterial density (P aeruginosa, Burkholderia cepacia complex, Achromobacter xylosoxidans, Stenotrophomonas maltophilia, and Staphylococcus aureus (including methicillin–resistant S aureus and small colony variants of S aureus [CFUs]) - change from Baseline in subject’s health-related quality of life (HRQOL): Cystic Fibrosis Questionnaire ; Timepoint(s) of evaluation of this end point: PHARMACOKINETICS - PK sampling: predose and at 1, 2, 4, and 6 hours postdose, at baseline and steady state (week 4 and/or week 8) CLINICAL ENDPOINTS - spirometry-based secondary endpoints: screening, baseline and at weeks 4 , 8, 12, 16, 24, 32, 40, 48, 52. - Pulmonary exacerbations checklist: baseline and at weeks 4 , 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 BIOMARKER ENDPOINTS - Sputum (DNA + elastase): baseline and at weeks 8, 24, 48 - serum hs-CRP: baseline and at weeks 4, 8, 12, 24, 32, 40, 48 and 52 EXPLORATORY ENDPOINTS - sputum bacterial density: baseline and at weeks 8, 24, 48 - health-related quality of life, Cystic Fibrosis Questionnaire: baseline and at weeks 12, 24, 48 | — |
Countries
Belgium, Canada, France, Germany, Italy, United Kingdom, United States
Contacts
Public ContactProject Management
Chiltern International Limited
Outcome results
None listed