A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
Sponsor
Vertex Pharmaceuticals Incorporated (Industry)
Overall Status
Completed
CT.gov ID
NCT04058353
Collaborator
(none)
271
93
2
9.5
2.9
0.3
Study Details
Study Description
Brief Summary
This study will evaluate the efficacy, safety and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a gating or residual function mutation (F/G and F/RF genotypes).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
271 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)
Actual Study Start Date
:
Aug 28, 2019
Actual Primary Completion Date
:
Jun 12, 2020
Actual Study Completion Date
:
Jun 12, 2020
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Control: IVA or TEZ/IVA Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks. |
Drug: IVA
Mono-tablet for oral administration.
Other Names:
Drug: TEZ/IVA
Fixed-dose combination (FDC) tablet for oral administration.
Other Names:
|
| Experimental: TC: ELX/TEZ/IVA Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. |
Drug: ELX/TEZ/IVA
FDC tablet for oral administration.
Other Names:
Drug: IVA
Mono-tablet for oral administration.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group [From Baseline Through Week 8]
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Secondary Outcome Measures
- Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group [From Baseline Through Week 8]
Sweat samples were collected using an approved collection device.
- Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group [From Baseline Through Week 8]
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
- Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group [From Baseline Through Week 8]
Sweat samples were collected using an approved collection device.
- Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group [From Baseline Through Week 8]
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
- Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group [From Baseline Through Week 8]
The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
- Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Day 1 up to Week 12]
Eligibility Criteria
Criteria
Ages Eligible for Study:
12 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a gating or residual function mutation (F/G and F/RF genotypes)
-
Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
Key Exclusion Criteria:
-
Clinically significant cirrhosis with or without portal hypertension
-
Lung infection with organisms associated with a more rapid decline in pulmonary status
-
Solid organ or hematological transplantation
Other protocol defined Inclusion/Exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35233 |
| 2 | Banner University of Arizona Medical Center | Tucson | Arizona | United States | 85724 |
| 3 | Miller Children's Hospital / Long Beach Memorial | Long Beach | California | United States | 90806 |
| 4 | Stanford University | Palo Alto | California | United States | 94304 |
| 5 | University of California Davis Medical Center | Sacramento | California | United States | 95817 |
| 6 | University of California San Francisco, Lung Transplant Program | San Francisco | California | United States | 94143 |
| 7 | National Jewish Health | Denver | Colorado | United States | 80206 |
| 8 | University of Miami Miller School of Medicine | Miami | Florida | United States | 33136 |
| 9 | Central Florida Pulmonary Group, PA | Orlando | Florida | United States | 32803 |
| 10 | Indiana University | Indianapolis | Indiana | United States | 46202 |
| 11 | The University of Iowa Hospitals and Clinics | Iowa City | Iowa | United States | 52242 |
| 12 | University of Kansas Medical Center | Kansas City | Kansas | United States | 66160 |
| 13 | University of Kentucky | Lexington | Kentucky | United States | 40536 |
| 14 | Massachusetts General Hospital Cystic Fibrosis Center Clinical Rsearch Center | Boston | Massachusetts | United States | 02114 |
| 15 | Boston Children's Hospital | Boston | Massachusetts | United States | 02115 |
| 16 | Michigan Medicine | Ann Arbor | Michigan | United States | 48109-5212 |
| 17 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 18 | Washington University School of Medicine / St. Louis Children's Hospital | Saint Louis | Missouri | United States | 63110 |
| 19 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 20 | Northwell Health- Long Island Jewish Medical Center | New Hyde Park | New York | United States | 11040 |
| 21 | Mount Sinai Beth Israel | New York | New York | United States | 10003 |
| 22 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 23 | University of North Carolina Hospitals | Chapel Hill | North Carolina | United States | 27514 |
| 24 | UC Health Holmes | Cincinnati | Ohio | United States | 45220 |
| 25 | Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center | Cleveland | Ohio | United States | 44106 |
| 26 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
| 27 | ProMedica Toledo Hospital/Toledo Children's Hospital/Pediatric Pulmonary & Cystic Fibrosis Center | Toledo | Ohio | United States | 43606 |
| 28 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 29 | Oregon Health & Science University | Portland | Oregon | United States | 97239 |
| 30 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 31 | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania | United States | 15224 |
| 32 | Dell Children's Medical Group | Austin | Texas | United States | 78723 |
| 33 | The University of Texas Southwestern Medical Center | Dallas | Texas | United States | 75390 |
| 34 | Texas Children's Hospital | Houston | Texas | United States | 77030 |
| 35 | University of Utah / Primary Children's Medical Center | Salt Lake City | Utah | United States | 84132 |
| 36 | University of Washington Medical Center | Seattle | Washington | United States | 98195 |
| 37 | University of Wisconsin Hospital and Clinics | Madison | Wisconsin | United States | 53792 |
| 38 | The Prince Charles Hospital | Chermside | Australia | ||
| 39 | Alfred Hospital | Melbourne, VIC | Australia | ||
| 40 | Perth Children's Hospital | Nedlands | Australia | ||
| 41 | The Royal Children's Hospital | Parkville, VIC | Australia | ||
| 42 | Mater Adult Hospital | South Brisbane | Australia | ||
| 43 | Queensland Children's Hospital | South Brisbane | Australia | ||
| 44 | Westmead Hospital | Westmead | Australia | ||
| 45 | Cliniques Universitaires de Bruxelles Hopital Erasme | Brussels | Belgium | ||
| 46 | Universitair Ziekenhuis Brussel - Campus Jette | Brussels | Belgium | ||
| 47 | Universitair Ziekenhuis Gent | Gent | Belgium | ||
| 48 | Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg | Leuven | Belgium | ||
| 49 | Stollery Children's Hospital | Edmonton | Canada | ||
| 50 | McGill University Health Center | Québec | Canada | ||
| 51 | St. Michael's Hospital | Toronto | Canada | ||
| 52 | St. Paul's Hospital | Vancouver | Canada | ||
| 53 | Juliane Marie Center, Rigshospitalet | Copenhagen | Denmark | ||
| 54 | Centre Hospitalier Lyon Sud | Benite Cedex | France | ||
| 55 | Groupe Hospitaler Pellegrin, CHU De Bordeaux | Bordeaux cedex | France | ||
| 56 | CHRU de Lille - Hopital Albert Calmette | Lille | France | ||
| 57 | CHU Marseille - Hopital Nord | Marseille | France | ||
| 58 | CHU de Montpellier - Hopital Arnaud de Villeneuve | Montpellier Cedex 5 | France | ||
| 59 | Hopital Necker, Enfants Malades | Paris Cedex 15 | France | ||
| 60 | Hopital Cochin | Paris | France | ||
| 61 | Hopital Pontchaillou CHU de Rennes | Rennes Cedex | France | ||
| 62 | Charite Paediatric Pulmonology Department | Berlin | Germany | ||
| 63 | Friedrich-Alexander University of Erlangen-Nuremberg, University Children's Hospital | Erlangen | Germany | ||
| 64 | Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen | Essen | Germany | ||
| 65 | Justus-Liebig-Universitaet Gießen Zentrum fur Kinderheilkunde und Jugendmedizin | Giessen | Germany | ||
| 66 | Universitätsklinikum Halle (Saale) / Universitätsklinik und Poliklinik für Innere Medizin, Schwerpunkt Pneumologie | Halle | Germany | ||
| 67 | Pneumologisches Studienzentrum Muenchen-West | Muenchen | Germany | ||
| 68 | University Hospital Wuerzburg | Würzburg | Germany | ||
| 69 | Cork University Hospital | Cork | Ireland | ||
| 70 | Beaumont Hospital | Dublin | Ireland | ||
| 71 | St. Vincent's University Hospital | Dublin | Ireland | ||
| 72 | University Hospital Limerick (Adults) | Limerick | Israel | ||
| 73 | Azienda Ospedaliero Universitaria Ospedale Riuniti | Ancona | Italy | ||
| 74 | IRCCS Istituto Giannina Gaslini-Ospedale Pediatrico | Genova | Italy | ||
| 75 | Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico | Milano | Italy | ||
| 76 | Malattie Apparato Respiratorio 2 - Fibrosi Cistica | Orbassano | Italy | ||
| 77 | Ospedale Pediatrico Bambino Gesu | Rome | Italy | ||
| 78 | Azienda Ospedaliera di Verona-Ospedale Civile Maggiore | Verona | Italy | ||
| 79 | HagaZiekenhuis van den Haag | Den Haag | Netherlands | ||
| 80 | University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis | Heidelberglaan | Netherlands | ||
| 81 | UMC St. Radboud | Nijmegen | Netherlands | ||
| 82 | Hospital Universitari Vall d´Hebron Servicio de Broncoscopia | Barcelona | Spain | ||
| 83 | Hospital Virgen de la Arrixaca | Murcia | Spain | ||
| 84 | Hospital Universitario Virgen del Rocio | Sevilla | Spain | ||
| 85 | Hospital Universitario y Politecnico La Fe | Valencia | Spain | ||
| 86 | Papworth Hospital NHS Foundation Trust, Papworth Everard | Cambridge | United Kingdom | ||
| 87 | Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital | Exeter | United Kingdom | ||
| 88 | Clinical Research Facility, Queen Elizabeth University Hospital | Glasgow | United Kingdom | ||
| 89 | St. James University Hospital | Leeds | United Kingdom | ||
| 90 | Liverpool Heart and Chest Hospital | Liverpool | United Kingdom | ||
| 91 | Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital | London | United Kingdom | ||
| 92 | Wythenshawe Hospital | Manchester | United Kingdom | ||
| 93 | Southampton General Hospital | Southampton | United Kingdom |
Sponsors and Collaborators
- Vertex Pharmaceuticals Incorporated
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT04058353
Other Study ID Numbers:
- VX18-445-104
- 2018-002835-76
First Posted:
Aug 15, 2019
Last Update Posted:
Jul 2, 2021
Last Verified:
Jun 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | A total of 271 participants were enrolled in this study out of which 12 participants discontinued in run-in period. Of 259 participants, 1 participant was randomized but not dosed in the treatment period. Therefore, results are presented for only 258 participants. |
|---|---|
| Pre-assignment Detail | This study was conducted in cystic fibrosis (CF) participants aged 12 years or older. |
| Arm/Group Title | Control: IVA or TEZ/IVA | Triple Combination (TC): ELX/TEZ/IVA |
|---|---|---|
| Arm/Group Description | Following an IVA (ivacaftor) or TEZ (tezacaftor)/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks. | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX (elexacaftor) 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. |
| Period Title: Overall Study | ||
| STARTED | 126 | 132 |
| COMPLETED | 122 | 131 |
| NOT COMPLETED | 4 | 1 |
Baseline Characteristics
| Arm/Group Title | Control: IVA or TEZ/IVA | TC: ELX/TEZ/IVA | Total |
|---|---|---|---|
| Arm/Group Description | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. | Total of all reporting groups |
| Overall Participants | 126 | 132 | 258 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
37.6
(14.3)
|
37.7
(14.7)
|
37.7
(14.5)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
61
48.4%
|
67
50.8%
|
128
49.6%
|
| Male |
65
51.6%
|
65
49.2%
|
130
50.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
4
3.2%
|
5
3.8%
|
9
3.5%
|
| Not Hispanic or Latino |
114
90.5%
|
117
88.6%
|
231
89.5%
|
| Unknown or Not Reported |
8
6.3%
|
10
7.6%
|
18
7%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Black or African American |
2
1.6%
|
0
0%
|
2
0.8%
|
| Not Collected per Local Regulations |
9
7.1%
|
9
6.8%
|
18
7%
|
| Aboriginal |
2
1.6%
|
1
0.8%
|
3
1.2%
|
| Latin-American |
1
0.8%
|
0
0%
|
1
0.4%
|
| Lebanese |
1
0.8%
|
0
0%
|
1
0.4%
|
| White |
110
87.3%
|
122
92.4%
|
232
89.9%
|
| White, American Indian or Alaska Native |
1
0.8%
|
0
0%
|
1
0.4%
|
| Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) (percentage points) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [percentage points] |
68.1
(16.4)
|
67.1
(15.7)
|
67.6
(16.0)
|
Outcome Measures
| Title | Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group |
|---|---|
| Description | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Time Frame | From Baseline Through Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set (FAS) included all randomized participants who have the intended CF transmembrane conductance regulator (CFTR) allele mutation and received at least 1 dose of study drug in the treatment period. This outcome measure was applicable only for the triple combination arm. |
| Arm/Group Title | TC: ELX/TEZ/IVA |
|---|---|
| Arm/Group Description | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. |
| Measure Participants | 132 |
| Least Squares Mean (95% Confidence Interval) [percentage points] |
3.7
|
| Title | Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group |
|---|---|
| Description | Sweat samples were collected using an approved collection device. |
| Time Frame | From Baseline Through Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. This outcome measure was applicable only for the triple combination group. |
| Arm/Group Title | TC: ELX/TEZ/IVA |
|---|---|
| Arm/Group Description | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. |
| Measure Participants | 132 |
| Least Squares Mean (95% Confidence Interval) [millimole per Liter (mmol/L)] |
-22.3
|
| Title | Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group |
|---|---|
| Description | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. |
| Time Frame | From Baseline Through Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. |
| Arm/Group Title | Control: IVA or TEZ/IVA | TC: ELX/TEZ/IVA |
|---|---|---|
| Arm/Group Description | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. |
| Measure Participants | 126 | 132 |
| Least Squares Mean (95% Confidence Interval) [percentage points] |
0.2
|
3.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TC: ELX/TEZ/IVA, TC: ELX/TEZ/IVA |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed-effects model for repeated measure | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares (LS) Mean Difference |
| Estimated Value | 3.5 | |
| Confidence Interval |
(2-Sided) 95% 2.2 to 4.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group |
|---|---|
| Description | Sweat samples were collected using an approved collection device. |
| Time Frame | From Baseline Through Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. |
| Arm/Group Title | Control: IVA or TEZ/IVA | TC: ELX/TEZ/IVA |
|---|---|---|
| Arm/Group Description | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. |
| Measure Participants | 126 | 132 |
| Least Squares Mean (95% Confidence Interval) [mmol/L] |
0.7
|
-22.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TC: ELX/TEZ/IVA, TC: ELX/TEZ/IVA |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed-effects model for repeated measure | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -23.1 | |
| Confidence Interval |
(2-Sided) 95% -26.1 to -20.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group |
|---|---|
| Description | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. |
| Time Frame | From Baseline Through Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. This outcome measure was applicable only for the triple combination arm. |
| Arm/Group Title | TC: ELX/TEZ/IVA |
|---|---|
| Arm/Group Description | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. |
| Measure Participants | 132 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
10.3
|
| Title | Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group |
|---|---|
| Description | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. |
| Time Frame | From Baseline Through Week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS. |
| Arm/Group Title | Control: IVA or TEZ/IVA | TC: ELX/TEZ/IVA |
|---|---|---|
| Arm/Group Description | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. |
| Measure Participants | 126 | 132 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
1.6
|
10.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | TC: ELX/TEZ/IVA, TC: ELX/TEZ/IVA |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed-effects model for repeated measure | |
| Comments | ||
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 8.7 | |
| Confidence Interval |
(2-Sided) 95% 5.3 to 12.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | |
| Time Frame | Day 1 up to Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety set included all participants who received at least 1 dose of study drug in the treatment period. |
| Arm/Group Title | Control: IVA or TEZ/IVA | TC: ELX/TEZ/IVA |
|---|---|---|
| Arm/Group Description | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. |
| Measure Participants | 126 | 132 |
| Participants With TEAEs |
83
65.9%
|
88
66.7%
|
| Participants With SAEs |
11
8.7%
|
5
3.8%
|
Adverse Events
| Time Frame | Day 1 up to Week 12 | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Control: IVA or TEZ/IVA | TC: ELX/TEZ/IVA | ||
| Arm/Group Description | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 mg q12h or TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. | Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. | ||
All Cause Mortality |
||||
| Control: IVA or TEZ/IVA | TC: ELX/TEZ/IVA | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/126 (0%) | 0/132 (0%) | ||
Serious Adverse Events |
||||
| Control: IVA or TEZ/IVA | TC: ELX/TEZ/IVA | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 11/126 (8.7%) | 5/132 (3.8%) | ||
| Ear and labyrinth disorders | ||||
| Tinnitus | 0/126 (0%) | 1/132 (0.8%) | ||
| Endocrine disorders | ||||
| Hyperparathyroidism primary | 1/126 (0.8%) | 0/132 (0%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis | 0/126 (0%) | 1/132 (0.8%) | ||
| Infections and infestations | ||||
| Cellulitis | 0/126 (0%) | 1/132 (0.8%) | ||
| Infective pulmonary exacerbation of cystic fibrosis | 7/126 (5.6%) | 2/132 (1.5%) | ||
| Pneumonia | 1/126 (0.8%) | 0/132 (0%) | ||
| Psychiatric disorders | ||||
| Anxiety | 1/126 (0.8%) | 0/132 (0%) | ||
| Depression | 1/126 (0.8%) | 0/132 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Haemoptysis | 1/126 (0.8%) | 1/132 (0.8%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Control: IVA or TEZ/IVA | TC: ELX/TEZ/IVA | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 47/126 (37.3%) | 35/132 (26.5%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 2/126 (1.6%) | 7/132 (5.3%) | ||
| Diarrhoea | 8/126 (6.3%) | 5/132 (3.8%) | ||
| Nausea | 9/126 (7.1%) | 2/132 (1.5%) | ||
| Infections and infestations | ||||
| Infective pulmonary exacerbation of cystic fibrosis | 10/126 (7.9%) | 2/132 (1.5%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 0/126 (0%) | 8/132 (6.1%) | ||
| Aspartate aminotransferase increased | 0/126 (0%) | 8/132 (6.1%) | ||
| Nervous system disorders | ||||
| Headache | 19/126 (15.1%) | 11/132 (8.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 18/126 (14.3%) | 3/132 (2.3%) | ||
| Sputum increased | 8/126 (6.3%) | 6/132 (4.5%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Results Point of Contact
| Name/Title | Medical Monitor |
|---|---|
| Organization | Vertex Pharmaceuticals Incorporated |
| Phone | 617-341-6777 |
| medicalinfo@vrtx.com |
Responsible Party:
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT04058353
Other Study ID Numbers:
- VX18-445-104
- 2018-002835-76
First Posted:
Aug 15, 2019
Last Update Posted:
Jul 2, 2021
Last Verified:
Jun 1, 2021