Cystic FibrosisPhase 3NCT03525548
A Study of VX-445 Combination Therapy in CF Subjects Homozygous for F508del (F/F)
A Phase 3 study testing VX-445/TEZ/IVA, TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 44 sites in 4 countries.
Trial summary
This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F) Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- VX-445/TEZ/IVA, TEZ/IVA and IVA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 113 participants
- Where
- 44 sitesin 4 countries
- Study dates
- 3 Aug 2018to 28 Dec 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Homozygous for the F508del mutation (F/F)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
Who cannot join
- 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
Trial locations and contacts
44 sites in 4 countries.
44 sites in 4 countries
United States28 sites
Massachusetts General Hospital Cystic Fibrosis Center Clinical Research Center
Boston, Massachusetts, 02114
UNC Marisco Clinical Research Center
Chapel Hill, North Carolina, 27517
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Virginia Primary Care Center
Charlottesville, Virginia, 22908
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Rainbow Babies and Children's Hospital/University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Vermont Lung Center
Colchester, Vermont, 05446
Nationwide Children's Hospital
Columbus, Ohio, 43205
The University of Texas Southwestern Medical Center
Dallas, Texas, 75390
Dayton Children's Hospital
Dayton, Ohio, 45404
National Jewish Health
Denver, Colorado, 80206
Harper University Hospital
Detroit, Michigan, 48201
Joe DiMaggio Cystic Fibrosis & Pulmonary Center/ Joe DiMaggio Children's Hospital/ Memorial Regional Hospital
Hollywood, Florida, 33021
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Miller Children's Hospital/ Long Beach Memorial
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027
Valley Children's Hospital
Madera, California, 93636
West Virginia University
Morgantown, West Virginia, 26506
Tulane Medical Center
New Orleans, Louisiana, 70112
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Central Florida Pulmonary Group, PA
Orlando, Florida, 32803
Nemours Children's Hospital
Orlando, Florida, 32827
Saint Francis Medical Center/ Children's Hospital of Illinoise/OSF
Peoria, Illinois, 61637
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Tampa General Hospital Cardiac and Lung Transplant Clinic
Tampa, Florida, 33606
ProMedica Toledo Hospital/ Toledo Children's Hospital/ Pediatric Pulmonary & Cystic Fibrosis Center
Toledo, Ohio, 43606
Banner University of Arizona Medical Center
Tucson, Arizona, 85724
New York Medical College
Valhalla, New York, 10595
United Kingdom6 sites
The Royal Belfast Hospital for Sick Children
Belfast
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
Birmingham
Royal Devon and Exeter NHS Foundation Trust, Royal Devon and Exeter Hospital
Exeter
Leeds General Infirmary
Leeds
King's College Hospital
London
Southampton General Hospital
Southampton
Belgium5 sites
Cliniques Universitaires de Bruxelles Hopital Erasme
Brussels
Universitair Ziekenhuis Brussel - Campus Jette
Brussels
UZ Antwerpen
Edegem
Universitair Ziekenhuis Gent
Ghent
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
Leuven
Netherlands5 sites
Academic Medical Center
Amsterdam
University Medical Center, Utrecht, Department of Pulmonology and Tuberculosis
Heidelberglaan
UMC St. Radboud
Nijmegen
Erasmus Medical Center
Rotterdam
HagaZiekenhuis van den Haag
The Hague
About this study
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 Homozygous for the F508del Mutation (F/F)
This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F)
- Conditions
- Cystic Fibrosis
- Being tested
- VX-445/TEZ/IVA, TEZ/IVA, IVA, Placebo
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VX-445/TEZ/IVADrug
Also called VX-445/VX-661/VX-770, VX-445/tezacaftor/ivacaftor
Participants received VX-445/TEZ/IVA orally once daily in the morning.
TEZ/IVADrug
Also called VX-661/VX-770, tezacaftor/ivacaftor
Participants received TEZ/IVA orally once daily in the morning.
IVADrug
Also called VX-770, ivacaftor
Participants received IVA orally once daily in the evening.
PlaceboDrug
Participants received placebo matched to VX-445/TEZ/IVA orally once daily in the morning.
PlaceboDrug
Participants received placebo matched TEZ/IVA orally once daily in the morning.
| Study group | Role | What they receive |
|---|---|---|
| TEZ/IVA | Active comparator | Following a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period. Receives: Drug: TEZ/IVA; Drug: IVA; Drug: Placebo |
| VX-445/TEZ/IVA TC | Experimental | Following a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. Receives: Drug: VX-445/TEZ/IVA; Drug: IVA; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Absolute Change 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.
Measured: From Baseline at Week 4
Secondary outcomes (4)
Absolute Change in Sweat Chloride (SwCl)
Sweat samples were collected using an approved collection device.
Measured: From Baseline at Week 4
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
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 indicate fewer symptoms and better health-related quality of life.
Measured: From Baseline at Week 4
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Measured: Day 1 and Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2018
- Study start3 Aug 2018
- Primary completion28 Dec 2018
- Study completion28 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 113 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03525548
- Sponsor's protocol ID
- VX17-445-103
- Other IDs
- 2018-000184-89, 2018
- Status last verified
- Jan 2020
- First submitted
- 2 May 2018
- Last updated
- 27 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Expanded access
- Available
Publications
Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31.
PubMed 31679946
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Homozygous for the F508del Mutation (F/F)
- ClinicalTrials.gov ID
- NCT03525548
- Acronym / sponsor ID
- VX17-445-103
- Conditions
- Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 113 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 3 Aug 2018 (actual)
- Primary completion
- 28 Dec 2018 (actual)
- Study completion
- 28 Dec 2018 (actual)
- First posted
- 15 May 2018 (actual)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the efficacy of VX-445 in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are homozygous for the F508del mutation (F/F)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TEZ/IVA | Active comparator | Drug: TEZ/IVA, Drug: IVA, Drug: PlaceboFollowing a run-in period of 4 weeks with Tezacaftor (TEZ)/Ivacaftor (IVA), participants received TEZ 100 milligram (mg)/IVA 150 mg as fixed-dose combination (FDC) tablet in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the triple combination (TC) treatment period. |
| VX-445/TEZ/IVA TC | Experimental | Drug: VX-445/TEZ/IVA, Drug: IVA, Drug: PlaceboFollowing a run-in period of 4 weeks with TEZ/IVA, participants received VX-445 200 mg/TEZ 100 mg/IVA 150 mg as FDC tablets in the morning and IVA 150 mg as mono tablet in the evening for 4 weeks in the TC treatment period. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Homozygous for the F508del mutation (F/F)
- Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VX-445/TEZ/IVAAlso: VX-445/VX-661/VX-770, VX-445/tezacaftor/ivacaftorParticipants received VX-445/TEZ/IVA orally once daily in the morning. | Drug | VX-445/TEZ/IVA TC |
| TEZ/IVAAlso: VX-661/VX-770, tezacaftor/ivacaftorParticipants received TEZ/IVA orally once daily in the morning. | Drug | TEZ/IVA |
| IVAAlso: VX-770, ivacaftorParticipants received IVA orally once daily in the evening. | Drug | TEZ/IVA, VX-445/TEZ/IVA TC |
| PlaceboParticipants received placebo matched to VX-445/TEZ/IVA orally once daily in the morning. | Drug | TEZ/IVA |
| PlaceboParticipants received placebo matched TEZ/IVA orally once daily in the morning. | Drug | VX-445/TEZ/IVA TC |
Primary outcome
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time frame: From Baseline at Week 4
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
4 secondary outcomes
Absolute Change in Sweat Chloride (SwCl)
Time frame: From Baseline at Week 4
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Time frame: From Baseline at Week 4
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to Week 8)
Observed Pre-Dose Concentration (Ctrough) of VX-445, TEZ, TEZ Metabolite (M1-TEZ), and IVA
Time frame: Day 1 and Week 4
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31679946Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, Mall MA, Welter JJ, Ramsey BW, McKee CM, Marigowda G, Moskowitz SM, Waltz D, Sosnay PR, Simard C, Ahluwalia N, Xuan F, Zhang Y, Taylor-Cousar JL, McCoy KS; VX17-445-103 Trial Group. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1940-1948. doi: 10.1016/S0140-6736(19)32597-8. Epub 2019 Oct 31.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
44 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing VX-445/TEZ/IVA, TEZ/IVA and IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 44 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, United Kingdom, Belgium, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) (time frame: From Baseline at Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03525548, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.