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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: CTX-4430

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).

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Hôpital Erasme
  • Leuven, Belgium
    • UZ Leuven
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • University of Calgary
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
• France
  • Dunkerque, France
    • Centre Hospitalier de Dunkerque
  • Grenoble, France
    • Hôpital Albert Michallon
  • Montpellier, France, Cedex 5
    • Hopital Arnaud de Villeneuve
  • Paris, France
    • Hôpital Cochin
  • Pierre Benite, France
    • CH Lyon Sud
• Germany
  • Berlin, Germany, 10117
    • Charite' University
  • Donaustauf, Germany
    • Krankenhaus Donaustauf
  • Dresden, Germany
    • Carl-Gustav-Klinikum Dresden, Mukoviszidose Centrum "Christiane Herzog"
  • Essen, Germany
    • Ruhrlandklinik Essen
  • Frankfurt, Germany
    • Klinikum der Johann Wolfgang Goethe-Universität
  • Frankfurt, Germany
    • Institut für klinische Forschung Pneumologie
  • Hannover, Germany
    • Medizinische Hochschule Hannover
  • Jena, Germany, 07740
    • Universitätsklinikum Jena CF Centre
  • München-Pasing, Germany
    • Lungenärztliche Praxis München-Pasing
  • Stuttgart, Germany
    • Klinikum Stuttgart CF Ambulanz
• Italy
  • Ancona, Italy
    • Ospedali Riuniti di Ancona
  • Catania, Italy
    • Azienda Ospedaliero Universitaria
  • Florence, Italy
    • Azienda Ospedaliera A Meyer
  • Rome, Italy
    • IRCCS Ospedale Pediatrico Bambino
  • Verona, Italy
    • Ospedale Civile Maggiore
• United Kingdom
  • Belfast, United Kingdom
    • Belfast City Hospital
  • Bristol, United Kingdom, BS2 8HW
    • Bristol Royal Infirmary
  • Cardiff, United Kingdom, CF64 2XX
    • LLandough Hospital
  • Leeds, United Kingdom, LS97TF
    • St James's University Hospital
  • Liverpool, United Kingdom
    • Liverpool Heart and Chest Hospital
  • London, United Kingdom
    • Royal Brompton Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • Manchester, United Kingdom
    • University Hospital of South Manchester
  • Newcastle Upon Tyne, United Kingdom
    • Royal Victoria Infirmary
  • Southampton, United Kingdom
    • University Hospital Southampton
  • Stoke on Trent, United Kingdom
    • Royal Stoke University Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Providence Health and Services
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Banner University of Arizona Medical Center
  • California
    • Los Angeles, California, United States, 90027
      • Childrens Hospital Los Angeles
    • Palo Alto, California, United States, 94304
      • Pediatric Pulmonary and Cystic Fibrosis Clinic, Stanford University
    • Sacramento, California, United States, 95817
      • University of California Davis Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Orlando, Florida, United States, 32803
      • Central Florida Pulmonary Group
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Peoria, Illinois, United States, 61637
      • St. Francis Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maine
    • Portland, Maine, United States, 04106
      • Maine Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 49286
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital
    • Grand Rapids, Michigan, United States, 49546
      • Spectrum Health Butterworth Campus
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Syracuse, New York, United States, 13210
      • Suny Upstate Medical University
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • UC Cincinnati Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19104
      • Drexel University
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Universiy of Tennessee Medical Center UHS
  • Texas
    • Austin, Texas, United States, 78723
      • Dell Children's Medical Center
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Hospital
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

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

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Week 48
Hazard Ratio Pulmonary Exacerbation for Participants With ppFEV1 >75 at Baseline	Hazard ratio of pulmonary exacerbation versus placebo for all subjects	Week 48
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.	Week 48
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.	Week 48
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	Week 48
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.	Week 48

Collaborators and Investigators

• Sponsor: Celtaxsys, Inc.
• Investigators: Principal Investigator: Steven Rowe, MD, University of Alabama at Birmingham, USA; Principal Investigator: Stuart Elborn, MD, Royal Brompton Hospital, London UK

Study record dates

Study Major Dates

• Study Start (Actual): October 30, 2015
• Primary Completion (Actual): April 20, 2018
• Study Completion (Actual): May 16, 2018

Study Registration Dates

• First Submitted: May 8, 2015
• First Submitted That Met QC Criteria: May 11, 2015
• First Posted (Estimate): May 14, 2015

Study Record Updates

• Last Update Posted (Actual): September 4, 2019
• Last Update Submitted That Met QC Criteria: August 22, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis
• Other Study ID Numbers: CTX-4430-CF-201