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

NCT04853368 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: M19-7712020-005805-25
• Study Type: interventional
• Target: 48
• Locations: 7 countries
• Sites: 41

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.

Conditions

Cystic Fibrosis (CF)

Keywords

Cystic Fibrosis (CF); Galicaftor; Navocaftor; ABBV-119; ABBV-576

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• 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 Vital Capacity (FVC)

  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 Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)

  Day 1 (Baseline) through Day 29

• Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC)

  Day 1 (Baseline) through Day 29

Study Arms (4)

F508del Homozygous Cystic Fibrosis (CF) Participants

EXPERIMENTAL

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; Drug: Navocaftor; Drug: ABBV-119

F508del Heterozygous CF Participants (Active Drug Group)

EXPERIMENTAL

F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days).

Drug: Galicaftor; Drug: Navocaftor; Drug: ABBV-119

F508del Heterozygous CF Participants (Placebo Group)

PLACEBO COMPARATOR

F508del heterozygous CF participants receive placebo (28 days).

Drug: Placebo

F508del Homozygous and Heterozygous CF Participants

EXPERIMENTAL

F508del homozygous and heterozygous CF participants receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days.

Drug: ABBV-576; Drug: Galicaftor; Drug: Navocaftor

Interventions

ABBV-576 DRUG

Oral capsules

F508del Homozygous and Heterozygous CF Participants

Galicaftor DRUG

Oral capsules

Also known as: ABBV-2222

F508del Heterozygous CF Participants (Active Drug Group); F508del Homozygous Cystic Fibrosis (CF) Participants; F508del Homozygous and Heterozygous CF Participants

Placebo DRUG

Oral capsules

F508del Heterozygous CF Participants (Placebo Group)

Navocaftor DRUG

Oral capsules

Also known as: ABBV-3067

F508del Heterozygous CF Participants (Active Drug Group); F508del Homozygous Cystic Fibrosis (CF) Participants; F508del Homozygous and Heterozygous CF Participants

ABBV-119 DRUG

Oral capsules

F508del Heterozygous CF Participants (Active Drug Group); F508del Homozygous Cystic Fibrosis (CF) Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \- Clinically significant laboratory values at screening that would pose undue risk for the participant or interfere with safety assessments (per the investigator).

Sponsors & Collaborators

• AbbVie: lead

Study Sites (41)

Velocity Clinical Research /ID# 248675

Mobile, Alabama, 36608-1771, United States

Location

University of Southern California /ID# 249147

Los Angeles, California, 90030, United States

Location

Ventura County Medical Center /ID# 248586

Ventura, California, 93003-1651, United States

Location

Central FL Pulmonary Orlando /ID# 245432

Orlando, Florida, 32803, United States

Location

University of Kansas Health Sy /ID# 249056

Kansas City, Kansas, 66160-8500, United States

Location

Boston Children's Hospital /ID# 248646

Boston, Massachusetts, 02115, United States

Location

Harper University Hospital /ID# 248917

Detroit, Michigan, 48201, United States

Location

Washington University-School of Medicine /ID# 245393

St Louis, Missouri, 63110, United States

Location

Dartmouth-Hitchcock Medical Center /ID# 245706

Lebanon, New Hampshire, 03756, United States

Location

Dartmouth Hitchcock Manchester /ID# 248795

Manchester, New Hampshire, 03104-4125, United States

Location

Albany Medical College-Pulmonary /ID# 248838

Albany, New York, 12208-3504, United States

Location

Northwell Health/Long Island Jewish Hospital /ID# 248916

New Hyde Park, New York, 11042, United States

Location

New York Medical College /ID# 248640

Valhalla, New York, 10595, United States

Location

UH Cleveland Medical Center /ID# 245433

Cleveland, Ohio, 44106, United States

Location

ProMedica Toledo Harris McIntosh /ID# 248627

Toledo, Ohio, 43606-3845, United States

Location

University of Oklahoma HSC /ID# 249190

Oklahoma City, Oklahoma, 73104-5410, United States

Location

Penn State Health /ID# 248585

Hershey, Pennsylvania, 17033, United States

Location

Medical University of South Carolina /ID# 245403

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University Medical Center /ID# 245400

Nashville, Tennessee, 37232, United States

Location

The Univ Texas HSC at Tyler /ID# 248498

Tyler, Texas, 75708, United States

Location

Children's Hospital of Richmond at VCU /ID# 248561

Richmond, Virginia, 23298, United States

Location

Medical College of Wisconsin - Plank Rd /ID# 249079

Milwaukee, Wisconsin, 53226-3548, United States

Location

Royal Prince Alfred Hospital /ID# 228781

Camperdown, New South Wales, 2050, Australia

Location

Westmead Hospital /ID# 227281

Westmead, New South Wales, 2145, Australia

Location

Mater Misericordiae Limited /ID# 227279

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital /ID# 228486

Adelaide, South Australia, 5000, Australia

Location

Alfred Health /ID# 227283

Melbourne, Victoria, 3004, Australia

Location

Royal Children's Hospital /ID# 227280

Parkville, Victoria, 3052, Australia

Location

Institute for Respiratory Health /ID# 227624

Nedlands, Western Australia, 6009, Australia

Location

Uza /Id# 228533

Edegem, Antwerpen, 2650, Belgium

Location

UZ Brussel /ID# 226607

Jette, Brussels Capital, 1090, Belgium

Location

UZ Gent /ID# 226605

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

Universitair Ziekenhuis Leuven /ID# 226608

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Orszagos Koranyi Pulmonologiai Intezet /ID# 228810

Budapest, 1121, Hungary

Location

Erasmus Medisch Centrum /ID# 234254

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Academisch Medisch Centrum /ID# 234253

Amsterdam, 1105 AZ, Netherlands

Location

HagaZiekenhuis /ID# 234138

The Hague, 2545 AA, Netherlands

Location

Greenlane Clinical Centre /ID# 227282

Epsom, Auckland, 1051, New Zealand

Location

Christchurch Hospital /ID# 227335

Christchurch, Canterbury, 8011, New Zealand

Location

Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica /ID# 228044

Banská Bystrica, 975 17, Slovakia

Location

Univerzitna nemocnica Bratislava Nemocnica Ruzinov /ID# 228042

Bratislava, 821 06, Slovakia

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

GLPG2222

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: April 21, 2021
• Study Start: September 20, 2021
• Primary Completion: June 5, 2023
• Study Completion: June 5, 2023
• Last Updated: July 16, 2024
• Results First Posted: July 16, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• 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/

Locations

US (22); SL (2); NL (3); AU (7); NZ (2); HU (1); BE (4)