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

Cystic Fibrosis (CF) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04853368
• Other study ID #: M19-771
• Secondary ID: 2020-005805-25
• Status: Terminated
• Phase: Phase 2
• Start date: September 20, 2021
• Est. completion date: June 5, 2023

Study information

• Verified date: June 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 48
• Est. completion date: June 5, 2023
• Est. primary completion date: June 5, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Cystic Fibrosis
• Cystic Fibrosis (CF)
• Fibrosis

Intervention

Drug:
• ABBV-576
Oral capsules
• Galicaftor
Oral capsules
• Placebo
Oral capsules
• Navocaftor
Oral capsules
• ABBV-119
Oral capsules

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital /ID# 228486	Adelaide	South Australia
Australia	Royal Prince Alfred Hospital /ID# 228781	Camperdown	New South Wales
Australia	Alfred Health /ID# 227283	Melbourne	Victoria
Australia	Institute for Respiratory Health /ID# 227624	Nedlands	Western Australia
Australia	Royal Children's Hospital /ID# 227280	Parkville	Victoria
Australia	Mater Misericordiae Limited /ID# 227279	South Brisbane	Queensland
Australia	Westmead Hospital /ID# 227281	Westmead	New South Wales
Belgium	Uza /Id# 228533	Edegem	Antwerpen
Belgium	UZ Gent /ID# 226605	Gent	Oost-Vlaanderen
Belgium	UZ Brussel /ID# 226607	Jette	Bruxelles-Capitale
Belgium	Universitair Ziekenhuis Leuven /ID# 226608	Leuven	Vlaams-Brabant
Hungary	Orszagos Koranyi Pulmonologiai Intezet /ID# 228810	Budapest
Netherlands	Academisch Medisch Centrum /ID# 234253	Amsterdam
Netherlands	HagaZiekenhuis /ID# 234138	Den Haag
Netherlands	Erasmus Medisch Centrum /ID# 234254	Rotterdam	Zuid-Holland
New Zealand	Christchurch Hospital /ID# 227335	Christchurch	Canterbury
New Zealand	Greenlane Clinical Centre /ID# 227282	Epsom	Auckland
Slovakia	Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica /ID# 228044	Banska Bystrica
Slovakia	Univerzitna nemocnica Bratislava Nemocnica Ruzinov /ID# 228042	Bratislava
United Kingdom	Royal Papworth Hospital NHS Foundation Trust /ID# 238629	Cambridge
United Kingdom	Cardiff & Vale University Health Board /ID# 238631	Cardiff	Wales
United Kingdom	NHS Greater Glasgow and Clyde /ID# 238630	Glasgow	Scotland
United Kingdom	Leeds Teaching Hospitals NHS Trust /ID# 238632	Leeds
United Kingdom	King's College Hospital NHS Foundation Trust /ID# 238628	London
United Kingdom	Royal Brompton and Harefield Hospitals /ID# 238635	London
United Kingdom	Manchester University NHS Foundation Trust /ID# 238637	Manchester	Lancashire
United Kingdom	Nottingham University Hospitals NHS Trust /ID# 238636	Nottingham	Nottinghamshire
United Kingdom	University Hospital Southampton NHS Foundation Trust /ID# 238634	Southampton	Hampshire
United States	Albany Medical College-Pulmonary /ID# 248838	Albany	New York
United States	Ascension Seton - Medical Park Tower /ID# 248643	Austin	Texas
United States	Boston Children's Hospital /ID# 248646	Boston	Massachusetts
United States	Medical University of South Carolina /ID# 245403	Charleston	South Carolina
United States	University of Cincinnati /ID# 249646	Cincinnati	Ohio
United States	UH Cleveland Medical Center /ID# 245433	Cleveland	Ohio
United States	Harper University Hospital /ID# 248917	Detroit	Michigan
United States	Penn State Health /ID# 248585	Hershey	Pennsylvania
United States	University of Kansas Health Sy /ID# 249056	Kansas City	Kansas
United States	Dartmouth-Hitchcock Medical Center /ID# 245706	Lebanon	New Hampshire
United States	University of Southern California /ID# 249147	Los Angeles	California
United States	Dartmouth Hitchcock Manchester /ID# 248795	Manchester	New Hampshire
United States	Medical College of Wisconsin - Plank Rd /ID# 249079	Milwaukee	Wisconsin
United States	Velocity Clinical Research /ID# 248675	Mobile	Alabama
United States	Vanderbilt University Medical Center /ID# 245400	Nashville	Tennessee
United States	Northwell Health/Long Island Jewish Hospital /ID# 248916	New Hyde Park	New York
United States	University of Oklahoma HSC /ID# 249190	Oklahoma City	Oklahoma
United States	Central FL Pulmonary Orlando /ID# 245432	Orlando	Florida
United States	Children's Hospital of Richmond at VCU /ID# 248561	Richmond	Virginia
United States	Washington University-School of Medicine /ID# 245393	Saint Louis	Missouri
United States	ProMedica Toledo Harris McIntosh /ID# 248627	Toledo	Ohio
United States	The Univ Texas HSC at Tyler /ID# 248498	Tyler	Texas
United States	New York Medical College /ID# 248640	Valhalla	New York
United States	Ventura County Medical Center /ID# 248586	Ventura	California

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Hungary,  Netherlands,  New Zealand,  Slovakia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	Absolute Change From Baseline in Forced Vital Capacity [FVC]	Forced vital capacity (FVC).	Up to 29 days
Secondary	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
Secondary	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
Secondary	Relative Changes From Baseline in Forced Vital Capacity [FVC]	Forced vital capacity (FVC).	Up to 29 days
Secondary	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
Secondary	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
Secondary	Cohort 3: Absolute Changes From Baseline in ppFEV1	Percent predicted forced expiratory volume in 1 second (ppFEV1).	Up to 29 days