Rheumatoid ArthritisPhase 2NCT01754935
A Magnetic Resonance Imaging Study and Arthroscopic Biopsy Substudy in Subjects With Active Rheumatoid Arthritis Receiving VX-509, an Oral JAK3 Inhibitor
A Phase 2 study testing VX-509 in people with Rheumatoid Arthritis, run by Vertex Pharmaceuticals Incorporated at 30 sites in 6 countries.
Trial summary
The current study is designed to evaluate the safety and efficacy, including MRI imaging, across a range of VX-509 doses in subjects with active rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- VX-509
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 30 sitesin 6 countries
- Study dates
- Jan 2013to Feb 2014
- Phase
- Phase 2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects 18 to 65 years of age (inclusive)
- Diagnosis of RA
- Swollen joint count of ≥6 out of 66 joints and tender joint count of ≥6 out of 68 joints
- Seropositivity based on either a positive rheumatoid factor or anti cyclic citrullinated peptide antibody at screening -OR- known erosive disease based on previous X-ray report or erosions detected on screening hand and foot X-ray
- Baseline CRP level or Westergren erythrocyte sedimentation rate ≥1.2 × upper limit of normal
- Receiving stable therapy with 1 of the following DMARDs: methotrexate, sulfasalazine, leflunomide, anti-malarial drug, or penicillamine
- Palpable 2+ synovitis of the wrist or ≥2 MCPs in the MRI-designated hand
Who cannot join
- History or presence of a clinically significant medical disorder other than RA that, in the opinion of the investigator and medical monitor, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
- Inflammatory, rheumatological disorders other than RA, where arthritis may be a prominent feature
- Planned surgery during the study
- History of alcohol or drug abuse, or excessive alcohol consumption
- History of tuberculosis (TB) infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment.
- Pregnant or nursing an infant or with a life partner who is pregnant, nursing, or planning to become pregnant
Trial locations and contacts
30 sites in 6 countries.
30 sites in 6 countries
United States21 sites
Vertex Investigational Site
Canton, Georgia
Vertex Investigational Site
Charleston, South Carolina
Vertex Investigational Site
Decatur, Georgia
Vertex Investigational Site
Duncansville, Pennsylvania
Vertex Investigational Site
Elizabethtown, Kentucky
Vertex Investigational Site
Fort Lauderdale, Florida
Vertex Investigational Site
Frederick, Maryland
Vertex Investigational Site
Greenboro, North Carolina
Vertex Investigational Site
Kansas City, Kansas
Vertex Investigational Site
Katy, Texas
Vertex Investigational Site
Lincoln, Nebraska
Vertex Investigational Site
Memphis, Tennessee
Vertex Investigational Site
Rochester, New York
Vertex Investigational Site
San Antonio, Texas
Vertex Investigational Site
Seattle, Washington
Vertex Investigational Site
Spokane, Washington
Vertex Investigational Site
Stanford, California
Vertex Investigational Site
Upland, California
Vertex Investigational Site
Venice, Florida
Vertex Investigational Site
Webster, Texas
Vertex Investigational Site
West Palm Beach, Florida
South Africa3 sites
Vertex Investigational Site
Johannesburg
Vertex Investigational Site
Pretoria
Vertex Investigational Site
Stellenbosch
Denmark2 sites
Vertex Investigational Site
Hillerød
Vertex Investigational Site
Hjørring
Netherlands2 sites
Vertex Investigational Site
Heerlen
Vertex Investigational Site
Utrecht
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of VX-509 Using Magnetic Resonance Imaging and Arthroscopic Biopsies in Subjects With Active Rheumatoid Arthritis on Stable Disease-Modifying Antirheumatic Drugs
The current study is designed to evaluate the safety and efficacy, including MRI imaging, across a range of VX-509 doses in subjects with active rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs).
Read the detailed description
VX-509 is an oral, selective Janus kinase 3 (JAK3) inhibitor being developed by Vertex. In autoimmune diseases, JAK3 is an essential component of the immune signaling cascade. This cascade ultimately contributes to abnormal immune response that results in chronic inflammation and, in the case of rheumatoid arthritis (RA), irreversible damage to cartilage and bones. Selective inhibition of JAK3 offers a new disease modifying approach to the treatment of RA, and a broad range of other autoimmune diseases.
- Conditions
- Rheumatoid Arthritis
- Being tested
- VX-509, VX-509 matching placebo
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VX-509Drug
50 mg oral tablet
VX-509 matching placeboDrug
0 mg oral tablet
| Study group | Role | What they receive |
|---|---|---|
| VX-509 100 mg qd Arm | Experimental | Not described Receives: Drug: VX-509 |
| VX-509 200 mg qd Arm | Experimental | Not described Receives: Drug: VX-509 |
| VX-509 300 mg qd Arm | Experimental | Not described Receives: Drug: VX-509 |
| Placebo Arm | Placebo comparator | Not described Receives: Drug: VX-509 matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects achieving a ≥20% improvement in disease severity according to the American College of Rheumatology criteria (ACR20), using C reactive protein (CRP) (ACR20 CRP)
Measured: Week 12
Change from baseline in Disease Activity Score 28 using CRP (4-component) (DAS28-4[CRP])
Measured: Week 12
Change from baseline in OMERACT RAMRIS synovitis score in designated hand wrist
Measured: Week 12
Change from baseline in OMERACT RAMRIS bone marrow edema (osteitis) in designated hand wrist
Measured: Week 12
Change from baseline in OMERACT RAMRIS erosion score in designated hand wrist
Measured: Week 12
Secondary outcomes (9)
Proportion of subjects achieving a ACR50 CRP and ACR70 CRP responses
Measured: Week 12
Proportion of subjects with DAS28 CRP <2.6, and those who achieve a remission, moderate response or good response according to the European League Against Rheumatism (EULAR) response criteria
Measured: Week 12
ACR hybrid scores
Measured: Week 12
Change from baseline in Health Assessment Questionnaire -Disability Index (HAQ-DI)
Measured: Week 12
Change from baseline in OMERACT RAMRIS synovitis, bone marrow edema (osteitis), erosion scores
Measured: Week 6
PK parameters of VX-509 and its metabolite in plasma (maximum observed concentration [Cmax] and area under the concentration versus time curve [AUC])
Measured: Week 12
Safety and tolerability as indicated by adverse events, laboratory tests, electrocardiograms (ECGs) and vital signs
Measured: Week 12
Change from baseline in the Physical Function subscale of the 36-item Short Form (SF-36)
Measured: Week 12
Change from baseline in the Physical Component and Mental Health Components of the SF-36
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2012 (estimated)
- Study startJan 2013
- Primary completionJan 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bradley Bloom, MD, FACR, FAAP, Study chair, Vertex Pharmaceuticals Incorporated
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01754935
- Sponsor's protocol ID
- VX12-509-103
- Other IDs
- 2012-003439-41
- Status last verified
- Apr 2015
- First submitted
- 18 Dec 2012
- Last updated
- 19 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Genovese MC, Yang F, Ostergaard M, Kinnman N. Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis: clinical and MRI findings. Ann Rheum Dis. 2016 Nov;75(11):1979-1983. doi: 10.1136/annrheumdis-2015-208901. Epub 2016 Apr 15.
PubMed 27084959
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of VX-509 Using Magnetic Resonance Imaging and Arthroscopic Biopsies in Subjects With Active Rheumatoid Arthritis on Stable Disease-Modifying Antirheumatic Drugs
- ClinicalTrials.gov ID
- NCT01754935
- Acronym / sponsor ID
- VX12-509-103
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- Jan 2013
- Primary completion
- Jan 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 21 Dec 2012 (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.
The current study is designed to evaluate the safety and efficacy, including MRI imaging, across a range of VX-509 doses in subjects with active rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs).
Detailed description
VX-509 is an oral, selective Janus kinase 3 (JAK3) inhibitor being developed by Vertex. In autoimmune diseases, JAK3 is an essential component of the immune signaling cascade. This cascade ultimately contributes to abnormal immune response that results in chronic inflammation and, in the case of rheumatoid arthritis (RA), irreversible damage to cartilage and bones. Selective inhibition of JAK3 offers a new disease modifying approach to the treatment of RA, and a broad range of other autoimmune diseases.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| VX-509 100 mg qd Arm | Experimental | Drug: VX-509 |
| VX-509 200 mg qd Arm | Experimental | Drug: VX-509 |
| VX-509 300 mg qd Arm | Experimental | Drug: VX-509 |
| Placebo Arm | Placebo comparator | Drug: VX-509 matching placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male and female subjects 18 to 65 years of age (inclusive)
- Diagnosis of RA
- Swollen joint count of ≥6 out of 66 joints and tender joint count of ≥6 out of 68 joints
- Seropositivity based on either a positive rheumatoid factor or anti cyclic citrullinated peptide antibody at screening -OR- known erosive disease based on previous X-ray report or erosions detected on screening hand and foot X-ray
- Baseline CRP level or Westergren erythrocyte sedimentation rate ≥1.2 × upper limit of normal
Key exclusion criteria (6 listed)
- History or presence of a clinically significant medical disorder other than RA that, in the opinion of the investigator and medical monitor, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
- Inflammatory, rheumatological disorders other than RA, where arthritis may be a prominent feature
- Planned surgery during the study
- History of alcohol or drug abuse, or excessive alcohol consumption
- History of tuberculosis (TB) infection of any kind (pulmonary or extrapulmonary, active or latent), regardless of history of anti-TB treatment.
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-50950 mg oral tablet | Drug | VX-509 100 mg qd Arm, VX-509 200 mg qd Arm, VX-509 300 mg qd Arm |
| VX-509 matching placebo0 mg oral tablet | Drug | Placebo Arm |
Primary outcome
Proportion of subjects achieving a ≥20% improvement in disease severity according to the American College of Rheumatology criteria (ACR20), using C reactive protein (CRP) (ACR20 CRP)
Time frame: Week 12
Change from baseline in Disease Activity Score 28 using CRP (4-component) (DAS28-4[CRP])
Time frame: Week 12
Change from baseline in OMERACT RAMRIS synovitis score in designated hand wrist
Time frame: Week 12
Change from baseline in OMERACT RAMRIS bone marrow edema (osteitis) in designated hand wrist
Time frame: Week 12
Change from baseline in OMERACT RAMRIS erosion score in designated hand wrist
Time frame: Week 12
9 secondary outcomes
Proportion of subjects achieving a ACR50 CRP and ACR70 CRP responses
Time frame: Week 12
Proportion of subjects with DAS28 CRP <2.6, and those who achieve a remission, moderate response or good response according to the European League Against Rheumatism (EULAR) response criteria
Time frame: Week 12
ACR hybrid scores
Time frame: Week 12
Change from baseline in Health Assessment Questionnaire -Disability Index (HAQ-DI)
Time frame: Week 12
Change from baseline in OMERACT RAMRIS synovitis, bone marrow edema (osteitis), erosion scores
Time frame: Week 6
PK parameters of VX-509 and its metabolite in plasma (maximum observed concentration [Cmax] and area under the concentration versus time curve [AUC])
Time frame: Week 12
Safety and tolerability as indicated by adverse events, laboratory tests, electrocardiograms (ECGs) and vital signs
Time frame: Week 12
Change from baseline in the Physical Function subscale of the 36-item Short Form (SF-36)
Time frame: Week 12
Change from baseline in the Physical Component and Mental Health Components of the SF-36
Time frame: Week 12
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 19 May 2015.
- Derived from this study: PubMed 27084959Genovese MC, Yang F, Ostergaard M, Kinnman N. Efficacy of VX-509 (decernotinib) in combination with a disease-modifying antirheumatic drug in patients with rheumatoid arthritis: clinical and MRI findings. Ann Rheum Dis. 2016 Nov;75(11):1979-1983. doi: 10.1136/annrheumdis-2015-208901. Epub 2016 Apr 15.
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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.
Bradley Bloom, MD, FACR, FAAP study chair
Vertex Pharmaceuticals Incorporated
30 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VX-509 in people with Rheumatoid Arthritis, run by Vertex Pharmaceuticals Incorporated at 30 sites in 6 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 7 inclusion and 6 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 19 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, South Africa, Denmark, Netherlands, Estonia and 1 more country. 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?
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?
Proportion of subjects achieving a ≥20% improvement in disease severity according to the American College of Rheumatology criteria (ACR20), using C reactive protein (CRP) (ACR20 CRP) (time frame: Week 12). The study lists 5 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 NCT01754935, 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 19 May 2015; AzTrials last refreshed its copy on 2 Nov 2026.