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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-005805-25 | EudraCT Number |
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Strategic considerations
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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.
Participants in Cohorts 1 and 3 will receive Open-label therapy. Participants in Cohorts 2 will receive Double-blinded therapy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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). |
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| F508del Heterozygous CF Participants (Active Drug Group) | Experimental | F508del heterozygous CF participants receive galicaftor/navocaftor/ABBV-119 combination therapy (28 days). |
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| F508del Heterozygous CF Participants (Placebo Group) | Placebo Comparator | F508del heterozygous CF participants receive placebo (28 days). |
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| F508del Homozygous and Heterozygous CF Participants | Experimental | F508del homozygous and heterozygous CF participants receive galicaftor/navocaftor/ABBV-576 triple combination therapy for 28 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ABBV-576 | Drug | Oral capsules |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 (Baseline) through Day 29 |
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Inclusion Criteria:
Exclusion Criteria:
- Clinically significant laboratory values at screening that would pose undue risk for the participant or interfere with safety assessments (per the investigator).
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| Name | Affiliation | Role |
|---|---|---|
| ABBVIE INC. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Velocity Clinical Research /ID# 248675 | Mobile | Alabama | 36608-1771 | United States | ||
| University of Southern California /ID# 249147 |
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
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/
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
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| ID | Title | Description |
|---|---|---|
| FG000 | C1(d-29 to -1) Dual Combo G + N | F508del Homozygous cystic fibrosis (CF) participants received Galicaftor/ Navocaftor dual combination (Day -29 to -1). Galicaftor: 300 mg QD, Oral capsules Navocaftor: 50 mg QD, Oral capsules |
| FG001 | C1(d1 - 29) Triple Combo G + N + ABBV-119 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part 1 (Day -29 to -1) |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 26, 2022 | Jun 3, 2024 |
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| Galicaftor |
| Drug |
Oral capsules |
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| Placebo | Drug | Oral capsules |
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| Navocaftor | Drug | Oral capsules |
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| ABBV-119 | Drug | Oral capsules |
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| 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. |
| Day 1 (Baseline) through Day 29 |
| 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. | Day 1 (Baseline) through Day 29 |
| 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. | Day 1 (Baseline) through Day 29 |
| 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. | Day 1 (Baseline) through Day 29 |
| 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. | Day 1 (Baseline) through Day 29 |
| 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. | Day 1 (Baseline) through Day 29 |
| 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. | Day 1 (Baseline) through Day 29 |
| Los Angeles |
| California |
| 90030 |
| United States |
| Ventura County Medical Center /ID# 248586 | Ventura | California | 93003-1651 | United States |
| Central FL Pulmonary Orlando /ID# 245432 | Orlando | Florida | 32803 | United States |
| University of Kansas Health Sy /ID# 249056 | Kansas City | Kansas | 66160-8500 | United States |
| Boston Children's Hospital /ID# 248646 | Boston | Massachusetts | 02115 | United States |
| Harper University Hospital /ID# 248917 | Detroit | Michigan | 48201 | United States |
| Washington University-School of Medicine /ID# 245393 | St Louis | Missouri | 63110 | United States |
| Dartmouth-Hitchcock Medical Center /ID# 245706 | Lebanon | New Hampshire | 03756 | United States |
| Dartmouth Hitchcock Manchester /ID# 248795 | Manchester | New Hampshire | 03104-4125 | United States |
| Albany Medical College-Pulmonary /ID# 248838 | Albany | New York | 12208-3504 | United States |
| Northwell Health/Long Island Jewish Hospital /ID# 248916 | New Hyde Park | New York | 11042 | United States |
| New York Medical College /ID# 248640 | Valhalla | New York | 10595 | United States |
| UH Cleveland Medical Center /ID# 245433 | Cleveland | Ohio | 44106 | United States |
| ProMedica Toledo Harris McIntosh /ID# 248627 | Toledo | Ohio | 43606-3845 | United States |
| University of Oklahoma HSC /ID# 249190 | Oklahoma City | Oklahoma | 73104-5410 | United States |
| Penn State Health /ID# 248585 | Hershey | Pennsylvania | 17033 | United States |
| Medical University of South Carolina /ID# 245403 | Charleston | South Carolina | 29425 | United States |
| Vanderbilt University Medical Center /ID# 245400 | Nashville | Tennessee | 37232 | United States |
| The Univ Texas HSC at Tyler /ID# 248498 | Tyler | Texas | 75708 | United States |
| Children's Hospital of Richmond at VCU /ID# 248561 | Richmond | Virginia | 23298 | United States |
| Medical College of Wisconsin - Plank Rd /ID# 249079 | Milwaukee | Wisconsin | 53226-3548 | United States |
| Royal Prince Alfred Hospital /ID# 228781 | Camperdown | New South Wales | 2050 | Australia |
| Westmead Hospital /ID# 227281 | Westmead | New South Wales | 2145 | Australia |
| Mater Misericordiae Limited /ID# 227279 | South Brisbane | Queensland | 4101 | Australia |
| Royal Adelaide Hospital /ID# 228486 | Adelaide | South Australia | 5000 | Australia |
| Alfred Health /ID# 227283 | Melbourne | Victoria | 3004 | Australia |
| Royal Children's Hospital /ID# 227280 | Parkville | Victoria | 3052 | Australia |
| Institute for Respiratory Health /ID# 227624 | Nedlands | Western Australia | 6009 | Australia |
| Uza /Id# 228533 | Edegem | Antwerpen | 2650 | Belgium |
| UZ Brussel /ID# 226607 | Jette | Brussels Capital | 1090 | Belgium |
| UZ Gent /ID# 226605 | Ghent | Oost-Vlaanderen | 9000 | Belgium |
| Universitair Ziekenhuis Leuven /ID# 226608 | Leuven | Vlaams-Brabant | 3000 | Belgium |
| Orszagos Koranyi Pulmonologiai Intezet /ID# 228810 | Budapest | 1121 | Hungary |
| Erasmus Medisch Centrum /ID# 234254 | Rotterdam | South Holland | 3015 GD | Netherlands |
| Academisch Medisch Centrum /ID# 234253 | Amsterdam | 1105 AZ | Netherlands |
| HagaZiekenhuis /ID# 234138 | The Hague | 2545 AA | Netherlands |
| Greenlane Clinical Centre /ID# 227282 | Epsom | Auckland | 1051 | New Zealand |
| Christchurch Hospital /ID# 227335 | Christchurch | Canterbury | 8011 | New Zealand |
| Fakultna nemocnica s poliklinikou F.D. Roosevelta Banska Bystrica /ID# 228044 | Banská Bystrica | 975 17 | Slovakia |
| Univerzitna nemocnica Bratislava Nemocnica Ruzinov /ID# 228042 | Bratislava | 821 06 | Slovakia |
F508del homozygous CF participants from Cohort 1(Day -29 to -1) who received G + N dual combination therapy followed by 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 |
| FG002 | C2(d1 - 29) Triple Combo G + N + ABBV-119 | 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 |
| FG003 | C2(d1 - 29) Placebo | F508del Heterozygous CF participants received placebo (Day 1 - 29). Placebo: Oral capsules |
| FG004 | C3 (d1 - 29) Triple Combo G + N + ABBV-576 for F508del Homo | F508del Homozygous CF participants received 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 |
| FG005 | C3 (d1 - 29) Triple Combo G + N + ABBV-576 for F508del Hetero | F508del Heterozygous CF participants received 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 |
| COMPLETED |
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| NOT COMPLETED |
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| Part 2 (Day 1-29) |
|
The Full Analysis Set (FAS) includes all enrolled subjects (randomized subjects for Cohort 2) who received at least 1 dose of study drug as dual or triple combination (or corresponding placebo). The FAS was used for demographics and baseline characteristics analyses.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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 |
| BG002 | Cohort 2 (d1 - 29) Placebo for F508del Heterozygous | F508del Heterozygous CF participants received placebo (Day 1 - 29). Placebo: Oral capsules |
| BG003 | 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 |
| BG004 | 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 |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) (%) at Baseline (Day 1) | Note: Percentages calculated on non-missing/non-unknown values. @ Baseline refers to (1) the last value before the first dose of the Dual Therapy for the Cohort 1 dual run-in summary, (2) the last value before the first dose of the Triple Therapy or matching placebo for the other summaries. & Subjects may have more than one microbiology history in the past year. Percentages were calculated based on N. | The number of participants analyzed for each Cohort varied from Overall analyzed as follows: Cohort 1 (N=24); Cohort 2 (N=13); Cohort 3 (N=11). | Mean | Standard Deviation | percent predicted FEV1 (%) |
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| Sweat Chloride (SwCl) in mmol/L at Baseline (Day 1) Cohort 3 | Note: @ Baseline refers to the last value before the first dose of the triple combination therapy. * The genotype information is based on the central lab test result. When this information is not available, the CFTR genotype documented at the screening visit is used. | The number of participants analyzed for each Cohort varied from Overall analyzed as follows: Cohort 1 (N=24); Cohort 2 (N=13); Cohort 3 (N=11). | Mean | Standard Deviation | mmol/L |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | 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. | Posted | Mean | Standard Deviation | percent predicted FEV1 (%ppFEV1) | Day 1 (Baseline) through Day 29 |
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| 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. | 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. | Posted | Mean | Full Range | Milli-mole/Liter (mmol/L) | Day 1 (Baseline) through Day 29 |
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| 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. | 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. | Posted | Mean | Standard Deviation | mmol/L | Day 1 (Baseline) through Day 29 |
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| 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. | 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. | Posted | Mean | Standard Deviation | Liters (L) | Day 1 (Baseline) through Day 29 |
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| 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. | 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. | Posted | Mean | Standard Deviation | Liters/second (L/sec) | Day 1 (Baseline) through Day 29 |
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| 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. | 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. | Posted | Mean | Standard Deviation | % ppFEV1 | Day 1 (Baseline) through Day 29 |
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| 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. | 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. | Posted | Mean | Standard Deviation | Liters (L) | Day 1 (Baseline) through Day 29 |
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| 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. | 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. | Posted | Mean | Standard Deviation | Liters/second (L/sec) | Day 1 (Baseline) through Day 29 |
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| 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. | 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. | Posted | Mean | Standard Deviation | score on a scale | Day 1 (Baseline) through Day 29 |
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| 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. | 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. | Posted | Mean | Full Range | % ppFEV1 | Day 1 (Baseline) through Day 29 |
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All-cause mortality is reported from enrollment to the end of study, median time on follow up in Part 1 was 28 days (d) for Cohort 1 (C1). In Part 2, was 28d for C1; 28 and 28d for C2; and 14, 20.5, and 14d for C3. Treatment-emergent AEs and serious AEs were collected from first dose of study drug until 30d after the last dose of study drug; mean duration on study drug in Part 1 was 28.2d for C1. In Part 2, was 25.8d for C1; 28 and 28.3d for C2; and 16.8, 20.5, and 17.5d for C3.
For Cohort 1 - Triple Combination Treatment arm, a TEAE was collected through day 56 and within 30 days after the last dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 (Day -29 to -1) Dual Combination Galicaftor + Navocaftor for F508del Homozygous | F508del Homozygous cystic fibrosis (CF) participants received Galicaftor/Navocaftor dual combination (Day -29 to -1). Galicaftor: 300 mg QD, Oral capsules Navocaftor: 50 mg QD, Oral capsules | 0 | 24 | 0 | 24 | 4 | 24 |
| EG001 | Cohort 1(Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-119 for F508del Homozygous | F508del homozygous CF participants from Cohort 1(Day -29 to -1) who received Galicaftor/ Navocaftor dual combination therapy. followed by 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 | 0 | 24 | 1 | 24 | 10 | 24 |
| EG002 | Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + 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 | 0 | 9 | 0 | 9 | 4 | 9 |
| EG003 | Cohort 2 (Day 1 - 29) Placebo F508del Heterozygous | F508del Heterozygous CF participants received placebo (Day 1 - 29). Placebo: Oral capsules | 0 | 4 | 0 | 4 | 2 | 4 |
| EG004 | Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Homozygous | F508del Homozygous CF participants received 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 | 0 | 9 | 1 | 9 | 7 | 9 |
| EG005 | Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Heterozygous | F508del Heterozygous CF participants received 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 | 0 | 2 | 0 | 2 | 2 | 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CYSTIC FIBROSIS | Congenital, familial and genetic disorders | MedDRA 26.0 | Systematic Assessment |
| |
| GENERAL PHYSICAL HEALTH DETERIORATION | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| INFECTIVE EXACERBATION OF BRONCHIECTASIS | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ABDOMINAL PAIN LOWER | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| ABDOMINAL PAIN UPPER | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| CONSTIPATION | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| DIARRHOEA | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| DISTAL INTESTINAL OBSTRUCTION SYNDROME | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| DYSPEPSIA | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| FLATULENCE | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| GASTROOESOPHAGEAL REFLUX DISEASE | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| NAUSEA | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| STEATORRHOEA | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| VOMITING | Gastrointestinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| CHEST DISCOMFORT | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| FATIGUE | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| INFLUENZA LIKE ILLNESS | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| NON-CARDIAC CHEST PAIN | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| PAIN | General disorders | MedDRA 26.0 | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| INFECTIVE PULMONARY EXACERBATION OF CYSTIC FIBROSIS | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| UPPER RESPIRATORY TRACT INFECTION | Infections and infestations | MedDRA 26.0 | Systematic Assessment |
| |
| NASAL INJURY | Injury, poisoning and procedural complications | MedDRA 26.0 | Systematic Assessment |
| |
| FORCED EXPIRATORY VOLUME DECREASED | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| FORCED VITAL CAPACITY DECREASED | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| SPIROMETRY ABNORMAL | Investigations | MedDRA 26.0 | Systematic Assessment |
| |
| DECREASED APPETITE | Metabolism and nutrition disorders | MedDRA 26.0 | Systematic Assessment |
| |
| BACK PAIN | Musculoskeletal and connective tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| HEADACHE | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| LETHARGY | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| POST-TRAUMATIC HEADACHE | Nervous system disorders | MedDRA 26.0 | Systematic Assessment |
| |
| CATARRH | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| DYSPNOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| DYSPNOEA EXERTIONAL | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| EPISTAXIS | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| HAEMOPTYSIS | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| RESPIRATORY TRACT CONGESTION | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| RHINORRHOEA | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| SPUTUM INCREASED | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| UPPER-AIRWAY COUGH SYNDROME | Respiratory, thoracic and mediastinal disorders | MedDRA 26.0 | Systematic Assessment |
| |
| NIGHT SWEATS | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
| |
| RASH | Skin and subcutaneous tissue disorders | MedDRA 26.0 | Systematic Assessment |
|
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Medical Services | AbbVie | 800-633-9110 | abbvieclinicaltrials@abbvie.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 31, 2023 | Jun 3, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000708865 | GLPG2222 |
Not provided
Not provided
Not provided
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| Cohort 2 (Day 1 - 29) |
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| Mixed Models Analysis |
Primary analysis of ppFEV1 using MMRM excludes data inconsistent with baseline in terms of the timing of bronchodilator or airway clearance regimen. |
| 0.254 |
One-sided p-value; p-value <=0.05 indicates significance. |
| LS Mean of Difference |
| 1.3 |
| Standard Error of the Mean |
| 1.92 |
| 2-Sided |
| 90 |
| -2.07 |
| 4.67 |
| Superiority |
| Mixed Models Analysis | Primary analysis of ppFEV1 using MMRM excludes data inconsistent with baseline in terms of the timing of bronchodilator or airway clearance regimen. | 0.402 | One-sided p-value; p-value <=0.05 indicates significance. | LS Mean of Difference | 0.9 | 2-Sided | 90 | -5.07 | 6.77 | Superiority |
| Units | Counts |
|---|---|
| Participants |
|
|
| OG002 |
| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous |
F508del Heterozygous CF participants received placebo (Day 1 - 29). Placebo: Oral capsules |
|
|
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| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous |
F508del Heterozygous CF participants received placebo (Day 1 - 29). Placebo: Oral capsules |
| OG003 | Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Homozygous | F508del Homozygous CF participants received 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 |
| OG004 | Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + 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 |
|
|
|
| OG002 | Cohort 2 (Day 1 - 29) Placebo F508del Heterozygous | F508del Heterozygous CF participants received placebo (Day 1 - 29). Placebo: Oral capsules |
| OG003 | Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + 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 |
| OG004 | Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + 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 |
|
|
|
| OG002 | Cohort 2 (Day 1 - 29) Placebo F508del Heterozygous | F508del Heterozygous CF participants received placebo (Day 1 - 29). Placebo: Oral capsules |
| OG003 | Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + 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 |
| OG004 | Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + 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 |
|
|
|
| Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous |
F508del Heterozygous CF participants received placebo (Day 1 - 29). Placebo: Oral capsules |
| OG003 | Cohort 3 (Day 1 - 29)Triple Combination Galicaftor + Navocaftor + 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 |
| OG004 | Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Heterozygous | F508del Heterozygous CF participants received 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 |
|
|
|
| OG002 | Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous | F508del Heterozygous CF participants received placebo (Day 1 - 29). Placebo: Oral capsules |
| OG003 | Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Homozygous | F508del Homozygous CF participants received 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 |
| OG004 | Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + 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 |
|
|
|
| OG001 | Cohort 2(Day 1 - 29) Triple Combination Galicaftor+ Navocaftor + 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 |
| OG002 | Cohort 2 (Day 1 - 29) Placebo for F508del Heterozygous | F508del Heterozygous CF participants received placebo (Day 1 - 29). Placebo: Oral capsules |
| OG003 | Cohort 3 (Day 1 - 29) Triple Combination Galicaftor + Navocaftor + 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 |
| OG004 | Cohort 3(Day 1 - 29)Triple Combination Galicaftor + Navocaftor + ABBV-576 for F508del Heterozygous | F508del Heterozygous CF participants received 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 |
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