Cystic FibrosisPhase 1NCT03029455
A Study to Evaluate Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Adults With Cystic Fibrosis
A Phase 1 study testing VX-659, Tezacaftor and Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 10 sites in United Kingdom.
Trial summary
Evaluate the safety and tolerability of VX-659 in healthy subjects Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- VX-659, Tezacaftor and Ivacaftor
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 163 participants
- Where
- 10 sitesUnited Kingdom
- Study dates
- Nov 2016to Aug 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy Volunteers: PARTS A, B, and C
- Males and Females of non-childbearing potential.
- Between the ages of 18 and 60 years inclusive
- Healthy, as defined per protocol.
- Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive
- Body weight >50 kg
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- CF Patients: PART D
- Body weight ≥35 kg.
- Males and Females of non-childbearing potential.
- Sweat chloride value ≥ 60 mmol/L at screening.
- Heterozygous for F508del and a minimal function CFTR mutation
- Forced expiratory volume in 1 second (FEV1) ≥40% and ≤90% of predicted at screening
Who cannot join
- Healthy Volunteers: PARTS A, B, and C
- History of any illness or any clinical condition that in the opinion of the investigator might confound the results of the study or pose additional risk to the subject.
- Any condition possibly affecting drug absorption.
- History of febrile illness within 14 days before the first study drug dose.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
- CF Patients: PART D
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- History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the subject.
- History of cirrhosis with portal hypertension.
- Risk factors for Torsade de Pointes.
- G6PD deficiency assessed at Screening.
- Abnormal Laboratory Values.
- Lung infection with organisms associated with a more rapid decline in pulmonary status
- History of solid organ or hematological transplantation.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United Kingdom10 sites
Study site
Birmingham
Study site
Cambridge
Study site
Exeter
Study site
Glasgow
Study site
Leeds
Study site
Liverpool
Study site
London
Study site
Manchester
Study site
Newcastle upon Tyne
Study site
Southampton
About this study
Official title: A Phase 1, Randomized, Double Blind, Placebo Controlled, Dose Escalation, and Bioavailability Study Evaluating the Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Subjects With Cystic Fibrosis
Evaluate the safety and tolerability of VX-659 in healthy subjects
- Conditions
- Cystic Fibrosis
- Being tested
- VX-659, Tezacaftor, Ivacaftor, VX-659 Matching Placebo, Triple Combination (TC) Matching Placebos
- 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-659Drug
TezacaftorDrug
Also called VX-661, TEZ
IvacaftorDrug
Also called VX-770, IVA
VX-659 Matching PlaceboDrug
Triple Combination (TC) Matching PlacebosDrug
| Study group | Role | What they receive |
|---|---|---|
| Part A: VX-659 or Matching Placebo | Experimental | Part A includes single-dose escalation. Receives: Drug: VX-659; Drug: VX-659 Matching Placebo |
| Part B: VX-659 or Matching Placebo | Experimental | Part B includes multiple-dose escalation. Receives: Drug: VX-659; Drug: VX-659 Matching Placebo |
| Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo | Experimental | Part C includes multiple dose escalation of VX-659 administered in Triple Combination (TC). Receives: Drug: VX-659; Drug: Tezacaftor; Drug: Ivacaftor; Drug: Triple Combination (TC) Matching Placebos |
| Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo | Experimental | Part D includes subjects with CF. Participants will receive TC or matching placebos. Receives: Drug: VX-659; Drug: Tezacaftor; Drug: Ivacaftor; Drug: Triple Combination (TC) Matching Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Measured: from baseline up to Day 50
Secondary outcomes (9)
Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL)
Measured: from baseline up to Day 18
Cmax of TEZ and selected metabolites (μg/mL)
Measured: from baseline up to Day 18
Cmax of IVA and selected metabolites (μg/mL)
Measured: from baseline up to Day 18
Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-659 and selected metabolites (μg,h/mL)
Measured: from baseline up to Day 18
AUCtau of TEZ and selected metabolites (μg,h/mL)
Measured: from baseline up to Day 18
AUCtau of IVA and selected metabolites (μg,h/mL)
Measured: from baseline up to Day 18
Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (μg/mL)
Measured: from baseline up to Day 18
Ctrough of TEZ and selected metabolites (μg/mL)
Measured: from baseline up to Day 18
Ctrough of IVA and selected metabolites (μg/mL)
Measured: from baseline up to Day 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2017 (estimated)
- Study startNov 2016
- Primary completionAug 2017
- Study completionAug 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 163 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
- NCT03029455
- Sponsor's protocol ID
- VX16-659-001
- Other IDs
- 2016-003048-35, 2016
- Status last verified
- Sep 2017
- First submitted
- 11 Jan 2017
- Last updated
- 5 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
PubMed 37983082Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
PubMed 33331662Davies JC, Moskowitz SM, Brown C, Horsley A, Mall MA, McKone EF, Plant BJ, Prais D, Ramsey BW, Taylor-Cousar JL, Tullis E, Uluer A, McKee CM, Robertson S, Shilling RA, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Rowe SM; VX16-659-101 Study Group. VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1599-1611. doi: 10.1056/NEJMoa1807119. Epub 2018 Oct 18.
PubMed 30334693
Study at a glance
From the registry record, last updated by the sponsor on 5 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double Blind, Placebo Controlled, Dose Escalation, and Bioavailability Study Evaluating the Safety and Pharmacokinetics of VX-659 in Healthy Subjects and in Subjects With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT03029455
- Acronym / sponsor ID
- VX16-659-001
- Conditions
- Cystic Fibrosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 163 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- Nov 2016
- Primary completion
- Aug 2017 (actual)
- Study completion
- Aug 2017 (actual)
- First posted
- 24 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluate the safety and tolerability of VX-659 in healthy subjects
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part A: VX-659 or Matching Placebo | Experimental | Drug: VX-659, Drug: VX-659 Matching PlaceboPart A includes single-dose escalation. |
| Part B: VX-659 or Matching Placebo | Experimental | Drug: VX-659, Drug: VX-659 Matching PlaceboPart B includes multiple-dose escalation. |
| Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo | Experimental | Drug: VX-659, Drug: Tezacaftor, Drug: Ivacaftor, Drug: Triple Combination (TC) Matching PlacebosPart C includes multiple dose escalation of VX-659 administered in Triple Combination (TC). |
| Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo | Experimental | Drug: VX-659, Drug: Tezacaftor, Drug: Ivacaftor, Drug: Triple Combination (TC) Matching PlacebosPart D includes subjects with CF. Participants will receive TC or matching placebos. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Healthy Volunteers: PARTS A, B, and C
- Males and Females of non-childbearing potential.
- Between the ages of 18 and 60 years inclusive
- Healthy, as defined per protocol.
- Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive
Key exclusion criteria (13 listed)
- Healthy Volunteers: PARTS A, B, and C
- History of any illness or any clinical condition that in the opinion of the investigator might confound the results of the study or pose additional risk to the subject.
- Any condition possibly affecting drug absorption.
- History of febrile illness within 14 days before the first study drug dose.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
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-659 | Drug | Part A: VX-659 or Matching Placebo, Part B: VX-659 or Matching Placebo, Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo, Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo |
| TezacaftorAlso: VX-661, TEZ | Drug | Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo, Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo |
| IvacaftorAlso: VX-770, IVA | Drug | Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo, Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo |
| VX-659 Matching Placebo | Drug | Part A: VX-659 or Matching Placebo, Part B: VX-659 or Matching Placebo |
| Triple Combination (TC) Matching Placebos | Drug | Part C: VX-659 in TC with TEZ/IVA or Matching Triple Placebo, Part D: VX-659 in TC with TEZ/IVA or Matching Triple Placebo |
Primary outcome
Safety and Tolerability assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs)
Time frame: from baseline up to Day 50
9 secondary outcomes
Maximum observed concentration (Cmax) of VX-659 and selected metabolites (μg/mL)
Time frame: from baseline up to Day 18
Cmax of TEZ and selected metabolites (μg/mL)
Time frame: from baseline up to Day 18
Cmax of IVA and selected metabolites (μg/mL)
Time frame: from baseline up to Day 18
Area under the concentration versus time curve during a dosing interval (AUCtau) of VX-659 and selected metabolites (μg,h/mL)
Time frame: from baseline up to Day 18
AUCtau of TEZ and selected metabolites (μg,h/mL)
Time frame: from baseline up to Day 18
AUCtau of IVA and selected metabolites (μg,h/mL)
Time frame: from baseline up to Day 18
Observed pre-dose concentration (Ctrough) of VX-659 and selected metabolites (μg/mL)
Time frame: from baseline up to Day 18
Ctrough of TEZ and selected metabolites (μg/mL)
Time frame: from baseline up to Day 18
Ctrough of IVA and selected metabolites (μg/mL)
Time frame: from baseline up to Day 18
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2017.
- Derived from this study: PubMed 37983082Heneghan M, Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2023 Nov 20;11(11):CD010966. doi: 10.1002/14651858.CD010966.pub4.
- Derived from this study: PubMed 33331662Southern KW, Murphy J, Sinha IP, Nevitt SJ. Corrector therapies (with or without potentiators) for people with cystic fibrosis with class II CFTR gene variants (most commonly F508del). Cochrane Database Syst Rev. 2020 Dec 17;12(12):CD010966. doi: 10.1002/14651858.CD010966.pub3.
- Derived from this study: PubMed 30334693Davies JC, Moskowitz SM, Brown C, Horsley A, Mall MA, McKone EF, Plant BJ, Prais D, Ramsey BW, Taylor-Cousar JL, Tullis E, Uluer A, McKee CM, Robertson S, Shilling RA, Simard C, Van Goor F, Waltz D, Xuan F, Young T, Rowe SM; VX16-659-101 Study Group. VX-659-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct 25;379(17):1599-1611. doi: 10.1056/NEJMoa1807119. Epub 2018 Oct 18.
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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.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VX-659, Tezacaftor and Ivacaftor in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 10 sites in United Kingdom.
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 12 inclusion and 13 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 5 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United Kingdom. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 assessments as determined by number of subjects with adverse events (AEs) and serious adverse events (SAEs) (time frame: from baseline up to Day 50). 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 NCT03029455, which also lists 3 linked publications.
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 5 Sep 2017.