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

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

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.

Study Overview

• Status: Terminated
• Conditions: Cystic Fibrosis (CF)
• Intervention / Treatment: Drug: Placebo; Drug: Galicaftor; Drug: Navocaftor; Drug: ABBV-119; Drug: ABBV-576

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital /ID# 228781
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital /ID# 227281
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Misericordiae Limited /ID# 227279
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital /ID# 228486
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health /ID# 227283
    • Parkville, Victoria, Australia, 3052
      • Royal Children's Hospital /ID# 227280
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Institute for Respiratory Health /ID# 227624
• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Uza /Id# 228533
  • Bruxelles-Capitale
    • Jette, Bruxelles-Capitale, Belgium, 1090
      • UZ Brussel /ID# 226607
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • UZ Gent /ID# 226605
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Universitair Ziekenhuis Leuven /ID# 226608
• Hungary
  • Budapest, Hungary, 1121
    • Orszagos Koranyi Pulmonologiai Intezet /ID# 228810
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum /ID# 234253
  • Den Haag, Netherlands, 2545 AA
    • HagaZiekenhuis /ID# 234138
  • Zuid-Holland
    • Rotterdam, Zuid-Holland, Netherlands, 3015 GD
      • Erasmus Medisch Centrum /ID# 234254
• New Zealand
  • Auckland
    • Epsom, Auckland, New Zealand, 1051
      • Greenlane Clinical Centre /ID# 227282
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8011
      • Christchurch Hospital /ID# 227335
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica /ID# 228044
  • Bratislava, Slovakia, 821 06
    • Univerzitna nemocnica Bratislava Nemocnica Ruzinov /ID# 228042
• United Kingdom
  • Cambridge, United Kingdom, CB2 0AY
    • Royal Papworth Hospital NHS Foundation Trust /ID# 238629
  • Leeds, United Kingdom, LS9 7TF
    • Leeds Teaching Hospitals NHS Trust /ID# 238632
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS Foundation Trust /ID# 238628
  • London, United Kingdom, SW3 6NP
    • Royal Brompton and Harefield Hospitals /ID# 238635
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • University Hospital Southampton NHS Foundation Trust /ID# 238634
  • Lancashire
    • Manchester, Lancashire, United Kingdom, M13 9WL
      • Manchester University NHS Foundation Trust /ID# 238637
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
      • Nottingham University Hospitals NHS Trust /ID# 238636
  • Scotland
    • Glasgow, Scotland, United Kingdom, G12 0XH
      • NHS Greater Glasgow and Clyde /ID# 238630
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XN
      • Cardiff & Vale University Health Board /ID# 238631
• United States
  • Alabama
    • Mobile, Alabama, United States, 36608-1771
      • Velocity Clinical Research /ID# 248675
  • California
    • Los Angeles, California, United States, 90030
      • University of Southern California /ID# 249147
    • Ventura, California, United States, 93003-1651
      • Ventura County Medical Center /ID# 248586
  • Florida
    • Orlando, Florida, United States, 32803
      • Central FL Pulmonary Orlando /ID# 245432
  • Kansas
    • Kansas City, Kansas, United States, 66160-8500
      • University of Kansas Health Sy /ID# 249056
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital /ID# 248646
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Harper University Hospital /ID# 248917
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University-School of Medicine /ID# 245393
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center /ID# 245706
    • Manchester, New Hampshire, United States, 03104-4125
      • Dartmouth Hitchcock Manchester /ID# 248795
  • New York
    • Albany, New York, United States, 12208-3504
      • Albany Medical College-Pulmonary /ID# 248838
    • New Hyde Park, New York, United States, 11042
      • Northwell Health/Long Island Jewish Hospital /ID# 248916
    • Valhalla, New York, United States, 10595
      • New York Medical College /ID# 248640
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0585
      • University of Cincinnati /ID# 249646
    • Cleveland, Ohio, United States, 44106
      • UH Cleveland Medical Center /ID# 245433
    • Toledo, Ohio, United States, 43606-3845
      • ProMedica Toledo Harris McIntosh /ID# 248627
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104-5410
      • University of Oklahoma HSC /ID# 249190
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health /ID# 248585
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina /ID# 245403
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center /ID# 245400
  • Texas
    • Austin, Texas, United States, 78705-1000
      • Ascension Seton - Medical Park Tower /ID# 248643
    • Tyler, Texas, United States, 75708
      • The Univ Texas HSC at Tyler /ID# 248498
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Children's Hospital of Richmond at VCU /ID# 248561
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3548
      • Medical College of Wisconsin - Plank Rd /ID# 249079

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Galicaftor; Oral capsules; Drug: Navocaftor; Oral capsules; Drug: ABBV-119; Oral capsules
Experimental: F508del Heterozygous CF Participants (Active Drug Group); F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days).	Drug: Galicaftor; Oral capsules; Drug: Navocaftor; Oral capsules; Drug: ABBV-119; Oral capsules
Placebo Comparator: F508del Heterozygous CF Participants (Placebo Group); F508del heterozygous CF participants receive placebo (28 days).	Drug: Placebo; Oral capsules
Experimental: F508del Homozygous and Heterozygous CF Participants; F508del homozygous and heterozygous CF participants receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days.	Drug: Galicaftor; Oral capsules; Drug: Navocaftor; Oral capsules; Drug: ABBV-576; Oral capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts 1 and 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	Percent predicted forced expiratory volume in 1 second (ppFEV1).	Up to 29 days
Cohort 3: Absolute change in Sweat Chloride (SwCl).	Sweat chloride (SwCl) concentration is a biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function.	Up to 29 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts 1 and 2: Absolute Change From Baseline in Sweat Chloride (SwCl)	SwCl concentration is a biomarker of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel function.	Up to 29 days
Absolute Change From Baseline in Forced Vital Capacity [FVC]	Forced vital capacity (FVC).	Up to 29 days
Absolute Change From Baseline in Forced Expiratory Flow at Mid-Lung Capacity [FEF25-75]	Forced expiratory flow between 25% and 75% of exhaled volume (FEF25-75).	Up to 29 days
Relative Changes From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	Percent predicted forced expiratory volume in 1 second (ppFEV1).	Up to 29 days
Relative Changes From Baseline in Forced Vital Capacity [FVC]	Forced vital capacity (FVC).	Up to 29 days
Relative Changes From Baseline in Forced Expiratory Flow Between 25% and 75% of Exhaled Volume (FEF25-75)	Forced expiratory flow between 25% and 75% of exhaled volume (FEF25-75).	Up to 29 days
Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline	The CFQ-R 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. Participants will complete the CFQ-R electronically via a tablet device.	Up to 29 days
Cohort 3: Absolute Changes From Baseline in ppFEV1	Percent predicted forced expiratory volume in 1 second (ppFEV1).	Up to 29 days

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2021
• Primary Completion (Actual): June 5, 2023
• Study Completion (Actual): June 5, 2023

Study Registration Dates

• First Submitted: April 19, 2021
• First Submitted That Met QC Criteria: April 19, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Cystic Fibrosis (CF); Galicaftor; Navocaftor; ABBV-119; ABBV-576
• 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: M19-771; 2020-005805-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes