Clinical trial NCT04853368: 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
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cystic Fibrosis (CF)
Keywords: Cystic Fibrosis (CF)
Galicaftor
Navocaftor
ABBV-119
ABBV-576
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2021-04-21
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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).

Primary outcomes:
measure: Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: Day 1 (Baseline) through Day 29
measure: Cohort 3: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L
timeFrame: Day 1 (Baseline) through Day 29
Secondary outcomes:
measure: Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L
timeFrame: Day 1 (Baseline) through Day 29
measure: Absolute Change From Baseline Through Day 29 in Forced Vital Capacity (FVC)
timeFrame: Day 1 (Baseline) through Day 29
measure: Absolute Change From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75)
timeFrame: Day 1 (Baseline) through Day 29
measure: Relative Changes From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: Day 1 (Baseline) through Day 29
measure: Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC)
timeFrame: Day 1 (Baseline) through Day 29
measure: Relative Changes From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75)
timeFrame: Day 1 (Baseline) through Day 29
measure: Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline.
timeFrame: Day 1 (Baseline) through Day 29
measure: Cohort 3: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
timeFrame: Day 1 (Baseline) through Day 29
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Velocity Clinical Research /ID# 248675
state: Alabama
city: Los Angeles
country: United States
facility: University of Southern California /ID# 249147
state: California
city: Ventura
country: United States
facility: Ventura County Medical Center /ID# 248586
state: California
city: Orlando
country: United States
facility: Central FL Pulmonary Orlando /ID# 245432
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Health Sy /ID# 249056
state: Kansas
city: Boston
country: United States
facility: Boston Children's Hospital /ID# 248646
state: Massachusetts
city: Detroit
country: United States
facility: Harper University Hospital /ID# 248917
state: Michigan
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 245393
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center /ID# 245706
state: New Hampshire
city: Manchester
country: United States
facility: Dartmouth Hitchcock Manchester /ID# 248795
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical College-Pulmonary /ID# 248838
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health/Long Island Jewish Hospital /ID# 248916
state: New York
city: Valhalla
country: United States
facility: New York Medical College /ID# 248640
state: New York
city: Cleveland
country: United States
facility: UH Cleveland Medical Center /ID# 245433
state: Ohio
city: Toledo
country: United States
facility: ProMedica Toledo Harris McIntosh /ID# 248627
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma HSC /ID# 249190
state: Oklahoma
city: Hershey
country: United States
facility: Penn State Health /ID# 248585
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina /ID# 245403
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center /ID# 245400
state: Tennessee
city: Tyler
country: United States
facility: The Univ Texas HSC at Tyler /ID# 248498
state: Texas
city: Richmond
country: United States
facility: Children's Hospital of Richmond at VCU /ID# 248561
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin - Plank Rd /ID# 249079
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital /ID# 228781
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital /ID# 227281
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae Limited /ID# 227279
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital /ID# 228486
state: South Australia
city: Melbourne
country: Australia
facility: Alfred Health /ID# 227283
state: Victoria
city: Parkville
country: Australia
facility: Royal Children's Hospital /ID# 227280
state: Victoria
city: Nedlands
country: Australia
facility: Institute for Respiratory Health /ID# 227624
state: Western Australia
city: Edegem
country: Belgium
facility: Uza /Id# 228533
state: Antwerpen
city: Jette
country: Belgium
facility: UZ Brussel /ID# 226607
state: Bruxelles-Capitale
city: Gent
country: Belgium
facility: UZ Gent /ID# 226605
state: Oost-Vlaanderen
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven /ID# 226608
state: Vlaams-Brabant
city: Budapest
country: Hungary
facility: Orszagos Koranyi Pulmonologiai Intezet /ID# 228810
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum /ID# 234254
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum /ID# 234253
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis /ID# 234138
city: Epsom
country: New Zealand
facility: Greenlane Clinical Centre /ID# 227282
state: Auckland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital /ID# 227335
state: Canterbury
city: Banska Bystrica
country: Slovakia
facility: Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica /ID# 228044
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava Nemocnica Ruzinov /ID# 228042
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: