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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04853368




Registration number
NCT04853368
Ethics application status
Date submitted
19/04/2021
Date registered
21/04/2021
Date last updated
22/06/2023

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2020-005805-25
Secondary ID [2] 0 0
M19-771
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic Fibrosis (CF) 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Cystic fibrosis
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Inflammatory and Immune System 0 0 0 0
Connective tissue diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABBV-576
Treatment: Drugs - Galicaftor
Treatment: Drugs - Placebo
Treatment: Drugs - Navocaftor
Treatment: Drugs - ABBV-119

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).

Experimental: F508del Heterozygous CF Participants (Active Drug Group) - F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days).

Placebo Comparator: F508del Heterozygous CF Participants (Placebo Group) - F508del heterozygous CF participants receive placebo (28 days).

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


Treatment: Drugs: ABBV-576
Oral capsules

Treatment: Drugs: Galicaftor
Oral capsules

Treatment: Drugs: Placebo
Oral capsules

Treatment: Drugs: Navocaftor
Oral capsules

Treatment: Drugs: ABBV-119
Oral capsules
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cohorts 1 and 2: Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Timepoint [1] 0 0
Up to 29 days
Primary outcome [2] 0 0
Cohort 3: Absolute change in Sweat Chloride (SwCl).
Timepoint [2] 0 0
Up to 29 days
Secondary outcome [1] 0 0
Cohorts 1 and 2: Absolute Change From Baseline in Sweat Chloride (SwCl)
Timepoint [1] 0 0
Up to 29 days
Secondary outcome [2] 0 0
Absolute Change From Baseline in Forced Vital Capacity [FVC]
Timepoint [2] 0 0
Up to 29 days
Secondary outcome [3] 0 0
Absolute Change From Baseline in Forced Expiratory Flow at Mid-Lung Capacity [FEF25-75]
Timepoint [3] 0 0
Up to 29 days
Secondary outcome [4] 0 0
Relative Changes From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Timepoint [4] 0 0
Up to 29 days
Secondary outcome [5] 0 0
Relative Changes From Baseline in Forced Vital Capacity [FVC]
Timepoint [5] 0 0
Up to 29 days
Secondary outcome [6] 0 0
Relative Changes From Baseline in Forced Expiratory Flow Between 25% and 75% of Exhaled Volume (FEF25-75)
Timepoint [6] 0 0
Up to 29 days
Secondary outcome [7] 0 0
Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline
Timepoint [7] 0 0
Up to 29 days
Secondary outcome [8] 0 0
Cohort 3: Absolute Changes From Baseline in ppFEV1
Timepoint [8] 0 0
Up to 29 days

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/06/2023
Sample size
Target
Accrual to date
Final
48
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital /ID# 228781 - Camperdown
Recruitment hospital [2] 0 0
Westmead Hospital /ID# 227281 - Westmead
Recruitment hospital [3] 0 0
Mater Misericordiae Limited /ID# 227279 - South Brisbane
Recruitment hospital [4] 0 0
Royal Adelaide Hospital /ID# 228486 - Adelaide
Recruitment hospital [5] 0 0
Alfred Health /ID# 227283 - Melbourne
Recruitment hospital [6] 0 0
Royal Children's Hospital /ID# 227280 - Parkville
Recruitment hospital [7] 0 0
Institute for Respiratory Health /ID# 227624 - Nedlands
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3004 - Melbourne
Recruitment postcode(s) [6] 0 0
3052 - Parkville
Recruitment postcode(s) [7] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New Hampshire
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oklahoma
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
South Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Tennessee
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Virginia
Country [17] 0 0
United States of America
State/province [17] 0 0
Wisconsin
Country [18] 0 0
Belgium
State/province [18] 0 0
Antwerpen
Country [19] 0 0
Belgium
State/province [19] 0 0
Bruxelles-Capitale
Country [20] 0 0
Belgium
State/province [20] 0 0
Oost-Vlaanderen
Country [21] 0 0
Belgium
State/province [21] 0 0
Vlaams-Brabant
Country [22] 0 0
Hungary
State/province [22] 0 0
Budapest
Country [23] 0 0
Netherlands
State/province [23] 0 0
Zuid-Holland
Country [24] 0 0
Netherlands
State/province [24] 0 0
Amsterdam
Country [25] 0 0
Netherlands
State/province [25] 0 0
Den Haag
Country [26] 0 0
New Zealand
State/province [26] 0 0
Auckland
Country [27] 0 0
New Zealand
State/province [27] 0 0
Canterbury
Country [28] 0 0
Slovakia
State/province [28] 0 0
Banska Bystrica
Country [29] 0 0
Slovakia
State/province [29] 0 0
Bratislava
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Hampshire
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Lancashire
Country [32] 0 0
United Kingdom
State/province [32] 0 0
Nottinghamshire
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Scotland
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Wales
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Cambridge
Country [36] 0 0
United Kingdom
State/province [36] 0 0
Leeds
Country [37] 0 0
United Kingdom
State/province [37] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04853368
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ABBVIE INC.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04853368