Cystic FibrosisPhase 2NCT03912233
A Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects With Cystic Fibrosis
A Phase 2 study testing VX-121, TEZ and VX-561 in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 26 sites in 5 countries.
Trial summary
The purpose of this study is to evaluate the safety, tolerability and efficacy of VX-121 combination therapy in subjects with cystic fibrosis (CF). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- VX-121, TEZ and VX-561
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 87 participants
- Where
- 26 sitesin 5 countries
- Study dates
- 30 Apr 2019to 10 Dec 2019
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Part 1: Heterozygous for F508del and an MF mutation (F/MF)
- Part 2: Homozygous for F508del (F/F)
- FEV1 value ≥40% and ≤90% of the predicted mean for age, sex, and height
Who cannot join
- History of clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- History of solid organ or hematological transplantation
- Other protocol-defined Inclusion/Exclusion criteria may apply
Trial locations and contacts
26 sites in 5 countries.
26 sites in 5 countries
United States12 sites
Boston Children's Hospital
Boston, Massachusetts, 02115
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Kentucky.
Lexington, Kentucky, 40536
Keck Medical Center of University of Southern California
Los Angeles, California, 90033
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Tulane Medical Center
New Orleans, Louisiana, 70112
Columbia University Medical Center
New York, New York, 10032
Kaiser Permanente
Oakland, California, 94611
Santiago Reyes, M.D.
Oklahoma City, Oklahoma, 73112
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229-3900
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157
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
United Kingdom5 sites
University Hospitals Birmingham NHS Foundation Trust
Birmingham
Royal Brompton & Harefield NHS Foundation Trust, Royal Brompton Hospital
London
Wythenshawe Hospital
Manchester
The Newcastle upon Tyne Hospitals NHS Foundation Trust, The Royal Victoria Infirmary
Newcastle upon Tyne
All Wales Adult Cystic Fibrosis Centre, University Hospital Llandough
Penarth
Germany3 sites
Charite Paediatric Pulmonology Department
Berlin
Ruhrlandklinik Westdeutsches Lungenzentrum am Klinikum Essen
Essen
Pneumologisches Studienzentrum Muenchen-West
München
About this study
Official title: A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis
The purpose of this study is to evaluate the safety, tolerability and efficacy of VX-121 combination therapy in subjects with cystic fibrosis (CF).
- Conditions
- Cystic Fibrosis
- Being tested
- VX-121, TEZ, VX-561, TEZ/IVA, IVA
- 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-121Drug
Tablets for oral administration.
TEZDrug
Also called VX-661, Tezacaftor
TEZ tablet for oral administration.
VX-561Drug
Also called CTP-656, Deutivacaftor (D-IVA)
Tablets for oral administration.
TEZ/IVADrug
Also called VX-661/VX-770, Tezacaftor/Ivacaftor
Fixed-dose combination tablets for oral administration.
IVADrug
Also called VX-770, Ivacaftor
Tablets for oral administration.
PlaceboDrug
Placebos matched to VX-121, TEZ, and VX-561 for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Placebo | Placebo comparator | Participants received placebo matched to VX-121/TEZ/VX-561 triple combination (TC) for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period. Receives: Drug: Placebo |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Experimental | Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period Receives: Drug: VX-121; Drug: TEZ; Drug: VX-561 |
| Part 1: VX-121/TEZ/VX-561 TC - Medium Dose | Experimental | Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. Receives: Drug: VX-121; Drug: TEZ; Drug: VX-561 |
| Part 1: VX-121/TEZ/VX-561 TC - High Dose | Experimental | Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. Receives: Drug: VX-121; Drug: TEZ; Drug: VX-561 |
| Part 2: TEZ/IVA | Active comparator | Following run-in period with TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period. Receives: Drug: TEZ/IVA; Drug: IVA |
| Part 2: VX-121/TEZ/VX-561 TC - High Dose | Experimental | Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period. Receives: Drug: VX-121; Drug: TEZ; Drug: VX-561 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)
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 Through Day 29
Secondary outcomes (3)
Absolute Change in Sweat Chloride (SwCl) Concentrations
Sweat samples were collected using an approved collection device.
Measured: From Baseline Through Day 29
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 indicating fewer symptoms and better health-related quality of life.
Measured: From Baseline at Day 29
Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561)
Measured: Pre-dose at Day 15 and Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Apr 2019
- Study start30 Apr 2019
- Primary completion10 Dec 2019
- Study completion10 Dec 2019
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 87 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
- NCT03912233
- Sponsor's protocol ID
- VX18-121-101
- Status last verified
- Mar 2023
- First submitted
- 10 Apr 2019
- Last updated
- 20 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing
Publications
Uluer AZ, MacGregor G, Azevedo P, Indihar V, Keating C, Mall MA, McKone EF, Ramsey BW, Rowe SM, Rubenstein RC, Taylor-Cousar JL, Tullis E, Yonker LM, Chu C, Lam AP, Nair N, Sosnay PR, Tian S, Van Goor F, Viswanathan L, Waltz D, Wang LT, Xi Y, Billings J, Horsley A; VX18-121-101; VX18-561-101 Study Groups. Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials. Lancet Respir Med. 2023 Jun;11(6):550-562. doi: 10.1016/S2213-2600(22)00504-5. Epub 2023 Feb 23.
PubMed 36842446
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-blind, Controlled Study to Evaluate the Safety and Efficacy of VX-121 Combination Therapy in Subjects Aged 18 Years and Older With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT03912233
- Acronym / sponsor ID
- VX18-121-101
- Conditions
- Cystic Fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 30 Apr 2019 (actual)
- Primary completion
- 10 Dec 2019 (actual)
- Study completion
- 10 Dec 2019 (actual)
- First posted
- 11 Apr 2019 (actual)
- Results
- Posted 20 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety, tolerability and efficacy of VX-121 combination therapy in subjects with cystic fibrosis (CF).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Part 1: Placebo | Placebo comparator | Drug: PlaceboParticipants received placebo matched to VX-121/TEZ/VX-561 triple combination (TC) for 4 weeks in the treatment period and placebo matched to TEZ/VX-561 for 18 days in the washout period. |
| Part 1: VX-121/TEZ/VX-561 TC - Low Dose | Experimental | Drug: VX-121, Drug: TEZ, Drug: VX-561Participants received VX-121 5 milligram (mg) once daily (qd)/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period |
| Part 1: VX-121/TEZ/VX-561 TC - Medium Dose | Experimental | Drug: VX-121, Drug: TEZ, Drug: VX-561Participants received VX-121 10 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. |
| Part 1: VX-121/TEZ/VX-561 TC - High Dose | Experimental | Drug: VX-121, Drug: TEZ, Drug: VX-561Participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/VX-561 150 mg qd for 18 days in the washout period. |
| Part 2: TEZ/IVA | Active comparator | Drug: TEZ/IVA, Drug: IVAFollowing run-in period with TEZ 100 mg qd/IVA 150 mg every 12 hours (q12h) for 4 weeks, participants received TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the treatment period and TEZ 100 mg/IVA 150 mg q12h for 4 weeks in the washout period. |
| Part 2: VX-121/TEZ/VX-561 TC - High Dose | Experimental | Drug: VX-121, Drug: TEZ, Drug: VX-561Following run-in period with TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks, participants received VX-121 20 mg qd/TEZ 100 mg qd/VX-561 150 mg qd TC for 4 weeks in the treatment period and TEZ 100 mg qd/IVA 150 mg q12h for 4 weeks in the washout period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Part 1: Heterozygous for F508del and an MF mutation (F/MF)
- Part 2: Homozygous for F508del (F/F)
- FEV1 value ≥40% and ≤90% of the predicted mean for age, sex, and height
Key exclusion criteria (4 listed)
- History of clinically significant cirrhosis with or without portal hypertension
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- History of 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-121Tablets for oral administration. | Drug | Part 1: VX-121/TEZ/VX-561 TC - High Dose, Part 1: VX-121/TEZ/VX-561 TC - Low Dose, Part 1: VX-121/TEZ/VX-561 TC - Medium Dose, Part 2: VX-121/TEZ/VX-561 TC - High Dose |
| TEZAlso: VX-661, TezacaftorTEZ tablet for oral administration. | Drug | Part 1: VX-121/TEZ/VX-561 TC - High Dose, Part 1: VX-121/TEZ/VX-561 TC - Low Dose, Part 1: VX-121/TEZ/VX-561 TC - Medium Dose, Part 2: VX-121/TEZ/VX-561 TC - High Dose |
| VX-561Also: CTP-656, Deutivacaftor (D-IVA)Tablets for oral administration. | Drug | Part 1: VX-121/TEZ/VX-561 TC - High Dose, Part 1: VX-121/TEZ/VX-561 TC - Low Dose, Part 1: VX-121/TEZ/VX-561 TC - Medium Dose, Part 2: VX-121/TEZ/VX-561 TC - High Dose |
| TEZ/IVAAlso: VX-661/VX-770, Tezacaftor/IvacaftorFixed-dose combination tablets for oral administration. | Drug | Part 2: TEZ/IVA |
| IVAAlso: VX-770, IvacaftorTablets for oral administration. | Drug | Part 2: TEZ/IVA |
| PlaceboPlacebos matched to VX-121, TEZ, and VX-561 for oral administration. | Drug | Part 1: Placebo |
Primary outcome
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)
Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1)
Time frame: From Baseline Through Day 29
FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
3 secondary outcomes
Absolute Change in Sweat Chloride (SwCl) Concentrations
Time frame: From Baseline Through Day 29
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score
Time frame: From Baseline at Day 29
Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ and Its Metabolite (M1-TEZ) and, VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561)
Time frame: Pre-dose at Day 15 and Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36842446Uluer AZ, MacGregor G, Azevedo P, Indihar V, Keating C, Mall MA, McKone EF, Ramsey BW, Rowe SM, Rubenstein RC, Taylor-Cousar JL, Tullis E, Yonker LM, Chu C, Lam AP, Nair N, Sosnay PR, Tian S, Van Goor F, Viswanathan L, Waltz D, Wang LT, Xi Y, Billings J, Horsley A; VX18-121-101; VX18-561-101 Study Groups. Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials. Lancet Respir Med. 2023 Jun;11(6):550-562. doi: 10.1016/S2213-2600(22)00504-5. Epub 2023 Feb 23.
- Individual participant dataSharing planned: No. Details on Vertex data sharing criteria and process for requesting access can be found at: https://www.vrtx.com/independent-research/clinical-trial-data-sharing
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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.
26 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VX-121, TEZ and VX-561 in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 26 sites in 5 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 3 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 20 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 26 sites in United States, Netherlands, United Kingdom, Germany, Portugal. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 20 Apr 2023). 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?
Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: From Day 1 Through Safety Follow-up (up to Day 75 for Part 1 and up to Day 85 for Part 2)). The study lists 2 primary outcomes in all. 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 NCT03912233, 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 20 Apr 2023.