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)

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.

participants in cohorts 1 and 3 will receive open-label therapy. participants in cohorts 2 will receive double-blinded therapy.

Eligibility criteria:
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).

Keywords: cystic fibrosis (cf) galicaftor navocaftor abbv-119 abbv-576