Study to Evaluate Adverse Events and Change in Disease Activity With Oral Capsules of Galicaftor/Navocaftor/ABBV-119 or Galicaftor/Navocaftor/ABBV-576 Combination Therapies in Adult Participants With Cystic Fibrosis
- Conditions
- Cystic Fibrosis (CF)
- Interventions
- Registration Number
- NCT04853368
- Lead Sponsor
- AbbVie
- Brief Summary
Cystic Fibrosis (CF) is a rare, life-threatening, genetic disease that affects the lungs and digestive system, significantly impairing the quality of life, with those affected having a median age of death at 40. The main objective of this study is to assess how safe and effective is the combination therapy of galicaftor/navocaftor/ABBV-119 or Galicaftor/Navocaftor/ABBV-576 in adult participants with CF who are homozygous or heterozygous for the F508del mutation in each arm.
Galicaftor/Navocaftor/ABBV-119 combination therapy and Galicaftor/Navocaftor/ABBV-576 is being developed as an investigational drug for the treatment of CF. Study doctors place participants in 1 of the 4 groups, called treatment arms. Each group receives a different treatment. Around 90 adult participants with a diagnosis of CF will be enrolled in the study around approximately 35 sites worldwide.
Participants in arm 1 will receive oral capsules of galicaftor/navocaftor dual combination for 28 days followed by galicaftor/navocaftor/ABBV-119 triple combination for 28 days. Participants in arms 2 and 3 will receive the galicaftor/navocaftor/ABBV-119 triple combination or placebo for 28 days. Participants in arm 4 will receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days. For all study arms, ABBV-576, galicaftor, navocaftor, will be given once daily and ABBV-119 twice a day.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
- Detailed Description
Participants in Cohorts 1 and 3 will receive Open-label therapy. Participants in Cohorts 2 will receive Double-blinded therapy.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 48
- Confirmed clinical diagnosis of cystic fibrosis (CF).
- Arm 1 participants with genotype homozygous for the F508del CF transmembrane conductance regulator (CFTR) mutation and not receiving elexacaftor/tezacaftor/ivacaftor (ETI) treatment .
- Arm 2 and 3 participants with genotype heterozygous for the F508del CFTR mutation and a minimal function mutation and not receiving ETI treatment.
- Arm 4 participants with genotype either homozygous or heterozygous for the F508del mutation. Participants must be receiving stable ETI treatment.
- Percent predicted forced expiratory volume in 1 second (ppFEV1) >= 40% and <=90% of predicted normal for age, gender and height at screening.
- For arms 1 and 2: sweat chloride (SwCl) >= 60 mmol/L at screening. For participants who participated in Study M19-530, it is acceptable to use a SwCl value that the central lab provided in Study M19-530 to establish eligibility.
- Weight >= 35 kg at screening and Day -28 for arm 1 or day 1 for arms 2 to 4.
- Clinically significant laboratory values at screening that would pose undue risk for the participant or interfere with safety assessments (per the investigator).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description F508del Heterozygous CF Participants (Placebo Group) Placebo F508del heterozygous CF participants receive placebo (28 days). F508del Heterozygous CF Participants (Active Drug Group) Navocaftor F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days). F508del Heterozygous CF Participants (Active Drug Group) ABBV-119 F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days). F508del Homozygous and Heterozygous CF Participants Galicaftor F508del homozygous and heterozygous CF participants receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days. F508del Homozygous Cystic Fibrosis (CF) Participants ABBV-119 F508del homozygous cystic fibrosis (CF) participants receive galicaftor/navocaftor dual combination (28 days) followed by galicaftor/navocaftor/ABBV-119 triple combination therapy (28 days). F508del Homozygous and Heterozygous CF Participants Navocaftor F508del homozygous and heterozygous CF participants receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days. F508del Homozygous Cystic Fibrosis (CF) Participants Navocaftor F508del homozygous cystic fibrosis (CF) participants receive galicaftor/navocaftor dual combination (28 days) followed by galicaftor/navocaftor/ABBV-119 triple combination therapy (28 days). F508del Homozygous and Heterozygous CF Participants ABBV-576 F508del homozygous and heterozygous CF participants receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days. F508del Heterozygous CF Participants (Active Drug Group) Galicaftor F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days). F508del Homozygous Cystic Fibrosis (CF) Participants Galicaftor F508del homozygous cystic fibrosis (CF) participants receive galicaftor/navocaftor dual combination (28 days) followed by galicaftor/navocaftor/ABBV-119 triple combination therapy (28 days).
- Primary Outcome Measures
Name Time Method Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Day 1 (Baseline) through Day 29 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration and is used as a measure of lung function. Mixed-effect model with repeated measures (MMRM) was used for the analyses.
Cohort 3: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L Day 1 (Baseline) through Day 29 Sweat collection was performed to evaluate sweat chloride concentration. SwCl is a biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) activity. Persons with CF have higher levels of chloride in their sweat. MMRM was used for the analysis.
- Secondary Outcome Measures
Name Time Method Relative Changes From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Day 1 (Baseline) through Day 29 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration and is used as a measure of lung function. MMRM was used for the analyses. Note: The primary analysis of ppFEV1 using MMRM excludes data that are inconsistent with baseline in terms of the timing of bronchodilator or airway clearance regimen.
Cohort 3: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Day 1 (Baseline) through Day 29 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration and is used as a measure of lung function. MMRM was used for the analyses. Note: The primary analysis of ppFEV1 using MMRM excludes data that are inconsistent with baseline in terms of the timing of bronchodilator or airway clearance regimen.
Absolute Change From Baseline Through Day 29 in Forced Vital Capacity (FVC) Day 1 (Baseline) through Day 29 FVC is the total amount of air exhaled during forced expiratory volume (FEV) test and is a lung function test that is measured during spirometry. MMRM was used for the analyses.
Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L Day 1 (Baseline) through Day 29 Sweat collection was performed to evaluate sweat chloride concentration. SwCl is a biomarker of CFTR activity. Persons with CF have higher levels of chloride in their sweat. MMRM was used for the analysis.
Absolute Change From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) Day 1 (Baseline) through Day 29 FEF25-75 is a lung function test that is measured during spirometry, and is defined as the forced expiratory flow between 25% and 75% of vital capacity (mid-lung capacity). MMRM was used for analyses.
Relative Changes From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) Day 1 (Baseline) through Day 29 FEF25-75 is a lung function test that is measured during spirometry, and is defined as the forced expiratory flow between 25% and 75% of vital capacity (mid-lung capacity). MMRM was used for analyses.
Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC) Day 1 (Baseline) through Day 29 FVC is the total amount of air exhaled during FEV test and is a lung function test that is measured during spirometry. MMRM was used for the analyses.
Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline. Day 1 (Baseline) through Day 29 The CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score is designed for use in participants with a diagnosis of cystic fibrosis and is designed to measure impact on overall health, daily life, perceived well-being, and symptoms. CFQ-R has a total of 50 questions. Questions 40, 41, 42, 44, 45, 46, scored 1, 2, 3, or 4, from worst to best, were used to calculate the respiratory domain score. The scaled score for the domain is calculated as 100 × (mean scores of all non-missing questions - 1) / 3, ranging from 0 to 100. If more than 3 questions in the domain have missing scores, the scaled score was set as missing. Note: The LS mean is estimated using the linear regression on the change in CFQ-R from baseline to day 29. The higher CFQ-R respiratory score indicates better health. A positive change in CFQ-R respiratory score since baseline indicates improved health quality, while a negative change indicates a decreased health quality.
Trial Locations
- Locations (41)
University of Southern California /ID# 249147
🇺🇸Los Angeles, California, United States
UH Cleveland Medical Center /ID# 245433
🇺🇸Cleveland, Ohio, United States
Boston Children's Hospital /ID# 248646
🇺🇸Boston, Massachusetts, United States
Institute for Respiratory Health /ID# 227624
🇦🇺Nedlands, Western Australia, Australia
University of Kansas Health Sy /ID# 249056
🇺🇸Kansas City, Kansas, United States
Dartmouth-Hitchcock Medical Center /ID# 245706
🇺🇸Lebanon, New Hampshire, United States
Medical University of South Carolina /ID# 245403
🇺🇸Charleston, South Carolina, United States
Alfred Health /ID# 227283
🇦🇺Melbourne, Victoria, Australia
Universitair Ziekenhuis Leuven /ID# 226608
🇧🇪Leuven, Vlaams-Brabant, Belgium
HagaZiekenhuis /ID# 234138
🇳🇱Den Haag, Netherlands
Univerzitna nemocnica Bratislava Nemocnica Ruzinov /ID# 228042
🇸🇰Bratislava, Slovakia
Uza /Id# 228533
🇧🇪Edegem, Antwerpen, Belgium
Dartmouth Hitchcock Manchester /ID# 248795
🇺🇸Manchester, New Hampshire, United States
University of Oklahoma HSC /ID# 249190
🇺🇸Oklahoma City, Oklahoma, United States
Harper University Hospital /ID# 248917
🇺🇸Detroit, Michigan, United States
Vanderbilt University Medical Center /ID# 245400
🇺🇸Nashville, Tennessee, United States
Velocity Clinical Research /ID# 248675
🇺🇸Mobile, Alabama, United States
Central FL Pulmonary Orlando /ID# 245432
🇺🇸Orlando, Florida, United States
Ventura County Medical Center /ID# 248586
🇺🇸Ventura, California, United States
New York Medical College /ID# 248640
🇺🇸Valhalla, New York, United States
Northwell Health/Long Island Jewish Hospital /ID# 248916
🇺🇸New Hyde Park, New York, United States
Washington University-School of Medicine /ID# 245393
🇺🇸Saint Louis, Missouri, United States
ProMedica Toledo Harris McIntosh /ID# 248627
🇺🇸Toledo, Ohio, United States
Penn State Health /ID# 248585
🇺🇸Hershey, Pennsylvania, United States
Royal Prince Alfred Hospital /ID# 228781
🇦🇺Camperdown, New South Wales, Australia
Medical College of Wisconsin - Plank Rd /ID# 249079
🇺🇸Milwaukee, Wisconsin, United States
The Univ Texas HSC at Tyler /ID# 248498
🇺🇸Tyler, Texas, United States
Children's Hospital of Richmond at VCU /ID# 248561
🇺🇸Richmond, Virginia, United States
Westmead Hospital /ID# 227281
🇦🇺Westmead, New South Wales, Australia
Mater Misericordiae Limited /ID# 227279
🇦🇺South Brisbane, Queensland, Australia
Royal Adelaide Hospital /ID# 228486
🇦🇺Adelaide, South Australia, Australia
UZ Gent /ID# 226605
🇧🇪Gent, Oost-Vlaanderen, Belgium
UZ Brussel /ID# 226607
🇧🇪Jette, Bruxelles-Capitale, Belgium
Orszagos Koranyi Pulmonologiai Intezet /ID# 228810
🇭🇺Budapest, Hungary
Erasmus Medisch Centrum /ID# 234254
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Academisch Medisch Centrum /ID# 234253
🇳🇱Amsterdam, Netherlands
Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica /ID# 228044
🇸🇰Banska Bystrica, Slovakia
Greenlane Clinical Centre /ID# 227282
🇳🇿Epsom, Auckland, New Zealand
Christchurch Hospital /ID# 227335
🇳🇿Christchurch, Canterbury, New Zealand
Albany Medical College-Pulmonary /ID# 248838
🇺🇸Albany, New York, United States
Royal Children's Hospital /ID# 227280
🇦🇺Parkville, Victoria, Australia