A Phase 2 Study of Galicaftor/Navocaftor/ABBV-119 or Galicaftor/Navocaftor/ABBV-576 Combination Therapies in Subjects With Cystic Fibrosis Who Are Homozygous or Heterozygous for the F508del Mutation
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Enrollment
- 48
- Locations
- 41
- Primary Endpoint
- Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •Clinically significant laboratory values at screening that would pose undue risk for the participant or interfere with safety assessments (per the investigator).
Arms & Interventions
F508del Homozygous Cystic Fibrosis (CF) Participants
F508del homozygous cystic fibrosis (CF) participants receive galicaftor/navocaftor dual combination (28 days) followed by galicaftor/navocaftor/ABBV-119 triple combination therapy (28 days).
Intervention: Galicaftor (Drug)
F508del Homozygous Cystic Fibrosis (CF) Participants
F508del homozygous cystic fibrosis (CF) participants receive galicaftor/navocaftor dual combination (28 days) followed by galicaftor/navocaftor/ABBV-119 triple combination therapy (28 days).
Intervention: Navocaftor (Drug)
F508del Homozygous Cystic Fibrosis (CF) Participants
F508del homozygous cystic fibrosis (CF) participants receive galicaftor/navocaftor dual combination (28 days) followed by galicaftor/navocaftor/ABBV-119 triple combination therapy (28 days).
Intervention: ABBV-119 (Drug)
F508del Heterozygous CF Participants (Active Drug Group)
F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days).
Intervention: Galicaftor (Drug)
F508del Heterozygous CF Participants (Active Drug Group)
F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days).
Intervention: Navocaftor (Drug)
F508del Heterozygous CF Participants (Active Drug Group)
F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days).
Intervention: ABBV-119 (Drug)
F508del Heterozygous CF Participants (Placebo Group)
F508del heterozygous CF participants receive placebo (28 days).
Intervention: Placebo (Drug)
F508del Homozygous and Heterozygous CF Participants
F508del homozygous and heterozygous CF participants receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days.
Intervention: ABBV-576 (Drug)
F508del Homozygous and Heterozygous CF Participants
F508del homozygous and heterozygous CF participants receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days.
Intervention: Galicaftor (Drug)
F508del Homozygous and Heterozygous CF Participants
F508del homozygous and heterozygous CF participants receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days.
Intervention: Navocaftor (Drug)
Outcomes
Primary Outcomes
Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time Frame: 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
Time Frame: 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 Outcomes
- Relative Changes From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)(Day 1 (Baseline) through Day 29)
- 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)
- Absolute Change From Baseline Through Day 29 in Forced Vital Capacity (FVC)(Day 1 (Baseline) through Day 29)
- Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L(Day 1 (Baseline) through Day 29)
- Absolute Change From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75)(Day 1 (Baseline) through Day 29)
- Relative Changes From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75)(Day 1 (Baseline) through Day 29)
- Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC)(Day 1 (Baseline) through Day 29)
- Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline.(Day 1 (Baseline) through Day 29)