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

Detailed Description

Participants in Cohorts 1 and 3 will receive Open-label therapy. Participants in Cohorts 2 will receive Double-blinded therapy.

• 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 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
    • 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
    • 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 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).

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; Other Names: ABBV-2222; Drug: Navocaftor; Oral capsules; Other Names: ABBV-3067; 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; Other Names: ABBV-2222; Drug: Navocaftor; Oral capsules; Other Names: ABBV-3067; 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; Other Names: ABBV-2222; Drug: Navocaftor; Oral capsules; Other Names: ABBV-3067; 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 Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	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.	Day 1 (Baseline) through Day 29
Cohort 3: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L	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.	Day 1 (Baseline) through Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute Change From Baseline Through Day 29 in Forced Vital Capacity (FVC)	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.	Day 1 (Baseline) through Day 29
Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L	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.	Day 1 (Baseline) through Day 29
Absolute Change From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75)	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.	Day 1 (Baseline) through Day 29
Relative Changes From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)	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.	Day 1 (Baseline) through Day 29
Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC)	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.	Day 1 (Baseline) through Day 29
Relative Changes From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75)	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.	Day 1 (Baseline) through Day 29
Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline.	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.	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)	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.	Day 1 (Baseline) through Day 29

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): July 16, 2024
• Last Update Submitted That Met QC Criteria: July 15, 2024
• Last Verified: July 1, 2024

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