Cystic Fibrosis (CF)
Conditions
Keywords
Cystic Fibrosis (CF), Galicaftor, Navocaftor, ABBV-119, ABBV-576
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.
Interventions
DRUGABBV-576
Oral capsules
DRUGGalicaftor
Oral capsules
DRUGPlacebo
Oral capsules
DRUGNavocaftor
Oral capsules
DRUGABBV-119
Oral capsules
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | Day 1 (Baseline) through Day 29 | 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. |
| Cohort 3: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L | Day 1 (Baseline) through Day 29 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | Day 1 (Baseline) through Day 29 | 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. |
| Relative Changes From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | Day 1 (Baseline) through Day 29 | 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. |
| Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC) | Day 1 (Baseline) through Day 29 | 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. |
| Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L | Day 1 (Baseline) through Day 29 | 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. |
| Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline. | Day 1 (Baseline) through Day 29 | 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. |
| Cohort 3: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | Day 1 (Baseline) through Day 29 | 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. |
| Relative Changes From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | Day 1 (Baseline) through Day 29 | 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. |
| Absolute Change From Baseline Through Day 29 in Forced Vital Capacity (FVC) | Day 1 (Baseline) through Day 29 | 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. |
Countries
Australia, Belgium, Hungary, Netherlands, New Zealand, Slovakia, United States
Participant flow
Pre-assignment details
In this 2-part study, Cystic Fibrosis (CF) participants either homozygous or heterozygous for F508del mutation were placed in cohorts based on genotype and treatment status of ETI therapy. In Part 1, Cohort 1(Day -29 to -1) (C1) completed Galicaftor + Navocaftor (G+N) dual combination therapy for 28 days (d) and automatically started Part 2. In Part 2, C1(d1 - 29) and C2(d1 - 29) received G+N+ABBV-119 triple combination, and C3(d1 -29) received G+N+ABBV-576 triple combination for 28d
Participants by arm
| Arm | Count |
|---|---|
| C1 (d -29 to -1) Dual Combo: G + N, and C1 (d1 - 29) Triple Combo: G + N + ABBV-119 for F508del Homo Cohort 1 (Day -29 to -1):
F508del Homozygous cystic fibrosis (CF) participants received Galicaftor/Navocaftor dual combination therapy:
Galicaftor: 300 mg QD, Oral capsules
Navocaftor: 50 mg QD, Oral capsules
Cohort 1 (Day 1 to 29):
F508del Homozygous cystic fibrosis CF participants from Cohort 1 (Day -29 to -2) dual combination who received Galicaftor/Navocaftor dual combination followed by Galicaftor/Navocaftor/ABBV-119 triple combination therapy:
Galicaftor: 300 mg QD, Oral capsules
Navocaftor: 50 mg QD, Oral capsules
ABBV-119: 210 mg BID, Oral capsules | 24 |
| Cohort 2 (d1 - 29) Triple Combo: G + N + ABBV-119 for F508del Heterozygous F508del Heterozygous CF participants received Galicaftor/Navocaftor/ABBV-119 triple combination therapy(Day 1 - 29).
Galicaftor: 300 mg QD, Oral capsules
Navocaftor: 50 mg QD, Oral capsules
ABBV-119: 210 mg BID, Oral capsules | 9 |
| Cohort 2 (d1 - 29) Placebo for F508del Heterozygous F508del Heterozygous CF participants received placebo (Day 1 - 29).
Placebo: Oral capsules | 4 |
| Cohort 3 (d1 - 29) Triple Combo: G + N + ABBV-576 for F508del Homozygous F508del Homozygous CF participants receive Galicaftor/Navocaftor/ABBV-576 triple combination therapy (Day 1 - 29).
Galicaftor: 300 mg QD, Oral capsules
Navocaftor: 50 mg QD, Oral capsules
ABBV-576: 5 mg QD, Oral capsules | 9 |
| Cohort 3 (d1 - 29) Triple Combo: G + N + ABBV-576 for F508del Heterozygous F508del Heterozygous CF participants received Galicaftor/nNavocaftor/ABBV-576 triple combination therapy (Day 1 - 29).
Galicaftor: 300 mg QD, Oral capsules
Navocaftor: 50 mg QD, Oral capsules
ABBV-576: 5 mg QD, Oral capsules | 2 |
| Total | 48 |
Baseline characteristics
| Characteristic | Cohort 2 (d1 - 29) Triple Combo: G + N + ABBV-119 for F508del Heterozygous | Cohort 2 (d1 - 29) Placebo for F508del Heterozygous | C1 (d -29 to -1) Dual Combo: G + N, and C1 (d1 - 29) Triple Combo: G + N + ABBV-119 for F508del Homo | Cohort 3 (d1 - 29) Triple Combo: G + N + ABBV-576 for F508del Homozygous | Cohort 3 (d1 - 29) Triple Combo: G + N + ABBV-576 for F508del Heterozygous | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 4 Participants | 24 Participants | 9 Participants | 2 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 4 Participants | 24 Participants | 9 Participants | 1 Participants | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) (%) at Baseline (Day 1) Cohort 1 (Day 1 - 29) | — | — | 57.0 percent predicted FEV1 (%) STANDARD_DEVIATION 14.63 | — | — | 57.0 percent predicted FEV1 (%) STANDARD_DEVIATION 14.63 |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) (%) at Baseline (Day 1) Cohort 2 (Day 1 - 29) | 62.9 percent predicted FEV1 (%) STANDARD_DEVIATION 18.27 | 67.3 percent predicted FEV1 (%) STANDARD_DEVIATION 19.97 | — | — | — | 64.2 percent predicted FEV1 (%) STANDARD_DEVIATION 18.07 |
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) (%) at Baseline (Day 1) Cohort 3 (Day 1 - 29) | — | — | — | 57.0 percent predicted FEV1 (%) STANDARD_DEVIATION 19.77 | 51.0 percent predicted FEV1 (%) STANDARD_DEVIATION 5.66 | 55.9 percent predicted FEV1 (%) STANDARD_DEVIATION 17.94 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 4 Participants | 24 Participants | 9 Participants | 2 Participants | 47 Participants |
| Region of Enrollment Australia | 5 participants | 2 participants | 8 participants | 1 participants | 0 participants | 16 participants |
| Region of Enrollment Hungary | 1 participants | 0 participants | 6 participants | 0 participants | 0 participants | 7 participants |
| Region of Enrollment Netherlands | 1 participants | 1 participants | 1 participants | 0 participants | 0 participants | 3 participants |
| Region of Enrollment New Zealand | 2 participants | 1 participants | 5 participants | 0 participants | 0 participants | 8 participants |
| Region of Enrollment Slovakia | 0 participants | 0 participants | 4 participants | 0 participants | 0 participants | 4 participants |
| Region of Enrollment United States | 0 participants | 0 participants | 0 participants | 8 participants | 2 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 9 Participants | 2 Participants | 2 Participants | 17 Participants |
| Sex: Female, Male Male | 6 Participants | 3 Participants | 15 Participants | 7 Participants | 0 Participants | 31 Participants |
| Sweat Chloride (SwCl) in mmol/L at Baseline (Day 1) Cohort 3 Cohort 1 (Day 1 - 29) | — | — | 76.71 mmol/L STANDARD_DEVIATION 13.127 | — | — | 76.71 mmol/L STANDARD_DEVIATION 13.127 |
| Sweat Chloride (SwCl) in mmol/L at Baseline (Day 1) Cohort 3 Cohort 2 (Day1 - 29) | 93.61 mmol/L STANDARD_DEVIATION 12.437 | 98.38 mmol/L STANDARD_DEVIATION 9.978 | — | — | — | 95.08 mmol/L STANDARD_DEVIATION 11.543 |
| Sweat Chloride (SwCl) in mmol/L at Baseline (Day 1) Cohort 3 Cohort 3 (Day 1 - 29) | — | — | — | 42.94 mmol/L STANDARD_DEVIATION 10.333 | 26.50 mmol/L STANDARD_DEVIATION 4.95 | 39.95 mmol/L STANDARD_DEVIATION 11.494 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 | 0 / 9 | 0 / 4 | 0 / 9 | 0 / 2 |
| other Total, other adverse events | 4 / 24 | 10 / 24 | 4 / 9 | 2 / 4 | 7 / 9 | 2 / 2 |
| serious Total, serious adverse events | 0 / 24 | 1 / 24 | 0 / 9 | 0 / 4 | 1 / 9 | 0 / 2 |
Outcome results
Primary
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.
Time frame: Day 1 (Baseline) through Day 29
Population: The Per-Protocol (PP) Population includes all enrolled subjects (randomized subjects for Cohort 2) who carry the intended CFTR mutation based on central lab report and received at least one dose of the Triple Therapy or placebo.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | Cohort 3: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L | 24 Milli-mole/Liter (mmol/L) |
| Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous | Cohort 3: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L | 40 Milli-mole/Liter (mmol/L) |
Primary
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.
Time frame: Day 1 (Baseline) through Day 29
Population: The Per-Protocol (PP) Population includes all enrolled subjects (randomized subjects for Cohort 2) who carry the intended CFTR mutation based on central lab report and received at least one dose of the Triple Therapy or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 2.2 percent predicted FEV1 (%ppFEV1) | Standard Deviation 3.68 |
| Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous | Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 2.6 percent predicted FEV1 (%ppFEV1) | Standard Deviation 5.62 |
| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous | Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | -2.0 percent predicted FEV1 (%ppFEV1) | Standard Deviation 6.63 |
p-value: 0.25490% CI: [-2.07, 4.67]Mixed Models Analysis
p-value: 0.40290% CI: [-5.07, 6.77]Mixed Models Analysis
p-value: 0.00290% CI: [1.22, 4.04]Mixed Models Analysis
Secondary
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.
Time frame: Day 1 (Baseline) through Day 29
Population: The Per-Protocol (PP) Population includes all enrolled subjects (randomized subjects for Cohort 2) who carry the intended CFTR mutation based on central lab report and received at least one dose of the Triple Therapy or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | Absolute Change From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | 0.067 Liters/second (L/sec) | Standard Deviation 0.2038 |
| Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous | Absolute Change From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | 0.134 Liters/second (L/sec) | Standard Deviation 0.2506 |
| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous | Absolute Change From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | -0.082 Liters/second (L/sec) | Standard Deviation 0.1947 |
| Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Homozygous | Absolute Change From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | -0.329 Liters/second (L/sec) | Standard Deviation 0.378 |
| Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Heterozygous | Absolute Change From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | -0.263 Liters/second (L/sec) | — |
p-value: 0.01790% CI: [0.0209, 0.1568]Mixed Models Analysis
p-value: 0.16990% CI: [-0.1814, 0.288]Mixed Models Analysis
p-value: 0.2390% CI: [-0.1809, 0.4527]Mixed Models Analysis
Secondary
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.
Time frame: Day 1 (Baseline) through Day 29
Population: The Per-Protocol (PP) Population includes all enrolled subjects (randomized subjects for Cohort 2) who carry the intended CFTR mutation based on central lab report and received at least one dose of the Triple Therapy or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | Absolute Change From Baseline Through Day 29 in Forced Vital Capacity (FVC) | 0.10 Liters (L) | Standard Deviation 0.256 |
| Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous | Absolute Change From Baseline Through Day 29 in Forced Vital Capacity (FVC) | 0.05 Liters (L) | Standard Deviation 0.269 |
| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous | Absolute Change From Baseline Through Day 29 in Forced Vital Capacity (FVC) | -0.07 Liters (L) | Standard Deviation 0.297 |
| Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Homozygous | Absolute Change From Baseline Through Day 29 in Forced Vital Capacity (FVC) | -0.22 Liters (L) | Standard Deviation 0.318 |
| Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Heterozygous | Absolute Change From Baseline Through Day 29 in Forced Vital Capacity (FVC) | -0.28 Liters (L) | — |
Comparison: Cohort 2: Difference between Triple Therapy and Placebop-value: 0.35290% CI: [-0.332, 0.212]Mixed Models Analysis
p-value: 0.00390% CI: [0.059, 0.219]Mixed Models Analysis
p-value: 0.47590% CI: [-0.162, 0.15]Mixed Models Analysis
Secondary
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.
Time frame: Day 1 (Baseline) through Day 29
Population: The Per-Protocol (PP) Population includes all enrolled subjects (randomized subjects for Cohort 2) who carry the intended CFTR mutation based on central lab report and received at least one dose of the Triple Therapy or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline. | 5.56 score on a scale | Standard Deviation 15.93 |
| Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous | Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline. | 10.32 score on a scale | Standard Deviation 19.092 |
| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous | Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline. | -5.56 score on a scale | Standard Deviation 21.754 |
| Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Homozygous | Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline. | -9.26 score on a scale | Standard Deviation 22.453 |
| Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Heterozygous | Absolute Change in CF Questionnaire-Revised (CFQ-R) Respiratory Domain Score From Baseline. | -22.22 score on a scale | — |
p-value: 0.05790% CI: [-0.26, 11.37]Mixed Models Analysis
p-value: 0.08890% CI: [-2.18, 19.4]Mixed Models Analysis
p-value: 0.14290% CI: [-6.9, 29.25]Mixed Models Analysis
Secondary
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.
Time frame: Day 1 (Baseline) through Day 29
Population: The Per-Protocol (PP) Population includes all enrolled subjects (randomized subjects for Cohort 2) who carry the intended CFTR mutation based on central lab report and received at least one dose of the Triple Therapy or placebo.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | Cohort 3: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | -5.7 % ppFEV1 |
| Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous | Cohort 3: Absolute Change From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | -9.0 % ppFEV1 |
Secondary
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.
Time frame: Day 1 (Baseline) through Day 29
Population: The Per-Protocol (PP) Population includes all enrolled subjects (randomized subjects for Cohort 2) who carry the intended CFTR mutation based on central lab report and received at least one dose of the Triple Therapy or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L | 5.7 mmol/L | Standard Deviation 10.78 |
| Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous | Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L | -11.5 mmol/L | Standard Deviation 16.61 |
| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous | Cohorts 1 and 2: Absolute Change From Baseline Through Day 29 in Sweat Chloride (SwCl) in mmol/L | 2.5 mmol/L | Standard Deviation 4.56 |
p-value: 0.02290% CI: [1.07, 9.92]Mixed Models Analysis
p-value: 0.04390% CI: [-27.59, -0.62]Mixed Models Analysis
Secondary
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.
Time frame: Day 1 (Baseline) through Day 29
Population: The Per-Protocol (PP) Population includes all enrolled subjects (randomized subjects for Cohort 2) who carry the intended CFTR mutation based on central lab report and received at least one dose of the Triple Therapy or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | Relative Changes From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | 4.553 Liters/second (L/sec) | Standard Deviation 13.2453 |
| Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous | Relative Changes From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | 8.701 Liters/second (L/sec) | Standard Deviation 12.9781 |
| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous | Relative Changes From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | -6.449 Liters/second (L/sec) | Standard Deviation 25.1954 |
| Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Homozygous | Relative Changes From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | -8.288 Liters/second (L/sec) | Standard Deviation 24.409 |
| Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Heterozygous | Relative Changes From Baseline Through Day 29 in Forced Expiratory Flow at Mid-Lung Capacity (FEF25-75) | -25.784 Liters/second (L/sec) | — |
p-value: 0.01890% CI: [1.4443, 11.5056]Mixed Models Analysis
p-value: 0.21490% CI: [-7.1464, 19.1844]Mixed Models Analysis
p-value: 0.28690% CI: [-15.186, 29.766]Mixed Models Analysis
Secondary
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.
Time frame: Day 1 (Baseline) through Day 29
Population: The Per-Protocol (PP) Population includes all enrolled subjects (randomized subjects for Cohort 2) who carry the intended CFTR mutation based on central lab report and received at least one dose of the Triple Therapy or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC) | 3.75 Liters (L) | Standard Deviation 7.006 |
| Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous | Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC) | 1.07 Liters (L) | Standard Deviation 6.524 |
| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous | Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC) | -2.06 Liters (L) | Standard Deviation 8.004 |
| Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Homozygous | Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC) | -6.01 Liters (L) | Standard Deviation 8.782 |
| Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Heterozygous | Relative Changes From Baseline Through Day 29 in Forced Vital Capacity (FVC) | -16.91 Liters (L) | — |
p-value: <0.00190% CI: [2.19, 6.524]Mixed Models Analysis
p-value: 0.39690% CI: [-4.449, 3.268]Mixed Models Analysis
p-value: 0.30590% CI: [-8.724, 4.732]Mixed Models Analysis
Secondary
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.
Time frame: Day 1 (Baseline) through Day 29
Population: The Per-Protocol (PP) Population includes all enrolled subjects (randomized subjects for Cohort 2) who carry the intended CFTR mutation based on central lab report and received at least one dose of the Triple Therapy or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | Relative Changes From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 3.8 % ppFEV1 | Standard Deviation 6.07 |
| Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + ABBV-119 for F508del Heterozygous | Relative Changes From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | 3.3 % ppFEV1 | Standard Deviation 8.15 |
| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous | Relative Changes From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | -4.9 % ppFEV1 | Standard Deviation 12.25 |
| Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Homozygous | Relative Changes From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | -9.1 % ppFEV1 | Standard Deviation 5.12 |
| Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Heterozygous | Relative Changes From Baseline Through Day 29 in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | -19.1 % ppFEV1 | — |
p-value: 0.00290% CI: [2.04, 6.78]Mixed Models Analysis
p-value: 0.3590% CI: [-4.42, 6.97]Mixed Models Analysis
p-value: 0.41290% CI: [-8.75, 11.34]Mixed Models Analysis