PsoriasisPhase 4NCT01971346
The Immunological Basis for Treatment Resistance to Anti-TNF Treatments
A Phase 4 study testing etanercept in people with Psoriasis, run by University of Michigan at 1 site in United States.
Trial summary
The purpose of this study is to determine the relationship between two types of cell signals, type I interferon (IFN) and tumor necrosis factor (TNF), in psoriatic skin prior to and during treatment with etanercept and correlate that information with the degree of the improvement in the psoriasis. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Psoriasis
- What is being tested?
- etanercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Mar 2014to 1 Nov 2017
- Phase
- Phase 4
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- At least 18 years of age at screening.
- Clinically stable moderate to severe plaque psoriasis at screening and baseline.
- Subject must be:
- A man or
- A woman who is surgically sterile or at least 3 years postmenopausal or
- A woman of childbearing potential who has had a negative pregnancy test within 7 days before the first dose of study drug.
- If the subject is sexually active, (s)he must agree to use a medically acceptable form of contraception during screening and throughout the study.
Who cannot join
- Grade 3 or 4 adverse events or infections within 28 days before screening, or between the screening visit and drug initiation.
- Active or chronic infection within 4 weeks before screening visit, or between the screening and baseline visits.
- Evidence of skin conditions other than psoriasis that would interfere with the evaluations of the effect of study medication on psoriasis.
- Use of oral psoralen with ultraviolet A (PUVA), oral retinoids, cyclosporine, alefacept, or any other systemic anti-psoriasis therapy within 28 days study drug initiation.
- Use of ulltraviolet B (UVB) therapy, topical steroids at no higher than moderate strength, topical vitamin A or D analog preparations, or anthralin with 14 days of study initiation.
- Prior or concurrent use of cyclophosphamide therapy
Show all 24Show fewer
- Concurrent sulfasalazine therapy.
- Known hypersensitivity to Enbrel® (etanercept) or any of its components or known to have antibodies to etanercept.
- Current enrollment in any other investigational device or investigational drug trial(s), or receipt of any other investigational agent(s) within 28 days before baseline visit.
- Use of any biologic drugs within 28 days of study drug initiation.
- Concurrent use of Anakinra.
- Severe comorbidities (diabetes mellitus requiring insulin; congestive heart failure (CHF) of any severity or myocardial infarction or cerebrovascular accident or transient ischemic attack within 3 months of screening visit; unstable angina pectoris, uncontrolled hypertension (sitting systolic blood pressure (BP) <80 mm Hg or > 160 or diastolic BP > 100 mm Hg), oxygen-dependent severe pulmonary disease, history of cancer within 5 years (other than resected cutaneous basal or squamous cell carcinoma of the skin or in situ cervical cancer)
- Known history of tuberculosis (TB), or previous positive purified protein derivative (PPD) test. Any mycobacterial disease or high risk factors for tuberculosis (TB), such as family member with TB, positive purified protein derivative (PPD) or taking anti-tuberculosis medication.
- Known HIV-positive status or known history of any other immuno-suppressing disease.
- Concurrent or history of psychiatric disease that would interfere with ability to comply with study protocol or give informed consent.
- History of alcohol or drug abuse within 12 months of screening visit.
- Latex sensitivity [Nota Bene: only applicable if they are using prefilled syringe or prefilled SureClick™ autoinjector presentations]
- Exposure to hepatitis B or hepatitis C or to high risk factors for hepatitis B or C, such as intravenous drug use in patient.
- Systemic lupus erythematosus, history of multiple sclerosis, transverse myelitis, optic neuritis or seizure disorder.
- Use of a live vaccine 90 days prior to screening visit, or concurrent use of a live vaccine.
- Any condition or circumstances judged by the patient's physician[or the investigator or medically qualified study staff] to render this clinical trial detrimental or otherwise unsuitable for the patient's participation.
- History of non-compliance with other therapies.
- Pregnant or nursing females.
- Diagnosis of multiple sclerosis in first degree family relationship (parent, sibling or child)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Michigan Department of Dermatology
Ann Arbor, Michigan, 48109
About this study
The purpose of this study is to determine the relationship between two types of cell signals, type I interferon (IFN) and tumor necrosis factor (TNF), in psoriatic skin prior to and during treatment with etanercept and correlate that information with the degree of the improvement in the psoriasis.
Read the detailed description
Hypothesis: The balance between type I IFN and TNF determines the response to anti-TNF treatment. The goal of the proposed study is to address this hypothesis and demonstrate that the strength of the type I IFN signature in psoriatic skin is the major determinant of the clinical response to anti-TNF treatment.
Purpose: Determine the strength of the type I interferon and TNF signal in psoriatic skin prior to and during treatment with etanercept and correlate with degree of clinical improvement.
Study Population: up to 50 subjects, men or women over the age of 18 with clinically stable plaque psoriasis, who meet the wash out requirements and other exclusion criteria
Psoriatic patients will receive 100 mg etanercept per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months.
Procedures: Urine pregnancy test, TB test, photography, Physical Examinations, Skin Examinations, Study Drug, Peripheral blood and biopsies
Anticipated Results: We expect that patients with strong IFN-α signature in psoriatic skin along with weak TNF-α signature will have minimal response to anti-TNF treatment, while patients with the opposite pattern, weak IFN and strong TNF signature, will have significant clinical improvement.
- Conditions
- Psoriasis
- Being tested
- etanercept
- Keywords
- Psoriasis, ENBREL, etanercept, anti-TNF
- Medical subject headings
- Psoriasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
etanerceptDrug
Also called ENBREL
100 mg Etanercept injections per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months
| Study group | Role | What they receive |
|---|---|---|
| Etanercept | Other | 100 mg Etanercept injections per week for 3 months. Receives: Drug: etanercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Psoriasis Area and Severity Index (PASI) Score
A cumulative change in PASI score from baseline to week 12 will be calculated for each patient. The PASI is the industry standard to decrease/eliminate subjectivity in determining psoriasis severity. It is a quantitative rating scale for measuring the severity of psoriatic lesions based on area coverage and plaque appearance. The severity of plaque characteristics (erythema, thickness and scaling) for body regions (head, upper limbs, trunk and lower limbs) is combined with the degree of plaque involvement in each body region to determine a single PASI score in the range of 0 (no disease) and 72 (maximal disease).
Measured: Baseline, 12 weeks
Secondary outcomes (3)
Tumor Necrosis Factor (TNF)-Alpha Signal Strength
Strength of TNF-alpha signatures will be measured in skin of study subjects at initiation, during and after treatment. The strength of these signals will be done using bioinformatic approach quantifying transcriptional signature of these cytokines. The strength of the cytokine signals will be treated as a response variable in a univariate repeated measure analysis of variance, with PASI response profile and time as covariates. PASI response profile will be categorized according to improvement in PASI score: responders (greater than 75% reduction in PASI from baseline), intermediate-responders (those with greater than 25% and less than 75% reduction in PASI from baseline), and non-responders (less than 25% reduction in PASI from baseline).
Measured: Baseline, Week 6, Week 12
Interferon (IFN)-Alpha Signal Strength
Strength of IFN-alpha signatures will be measured in skin of study subjects at initiation, during and after treatment. The strength of these signals in skin will be done using bioinformatic approach quantifying transcriptional signature of these cytokines. The strength of the cytokine signals will be treated as a response variable in a univariate repeated measure analysis of variance, with PASI response profile and time as covariates. PASI response profile will be categorized according to improvement in PASI score: responders (greater than 75% reduction in PASI from baseline), intermediate-responders (those with greater than 25% and less than 75% reduction in PASI from baseline), and non-responders (less than 25% reduction in PASI from baseline).
Measured: Baseline, Week 6, Week 12
Psoriasis Area and Severity Index (PASI) Response Profile
Subjects will be categorized according to improvement in Psoriasis Area and Severity Index (PASI) score: responders (greater than 75% reduction in PASI from baseline), intermediate-responders (those with greater than 25% and less than 75% reduction in PASI from baseline), and non-responders (less than 25% reduction in PASI from baseline).
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2013 (estimated)
- Study start13 Mar 2014
- Primary completion1 Nov 2017
- Study completion1 Nov 2017
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.
- Other trials for PsoriasisStudies of the same condition, open and under way.
- More trials run by University of MichiganThe 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Principal investigator, Johann E Gudjonsson MD, PhD, University of Michigan
- Investigators
- Johann Gudjonsson, MD PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01971346
- Sponsor's protocol ID
- Derm 652
- Status last verified
- Mar 2020
- First submitted
- 23 Oct 2013
- Last updated
- 4 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Immunological Basis for Treatment Resistance to Anti-TNF Treatments
- ClinicalTrials.gov ID
- NCT01971346
- Acronym / sponsor ID
- Derm 652
- Conditions
- Psoriasis
- Keywords
- Psoriasis, ENBREL, etanercept, anti-TNF
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- Amgen
- Study start
- 13 Mar 2014 (actual)
- Primary completion
- 1 Nov 2017 (actual)
- Study completion
- 1 Nov 2017 (actual)
- First posted
- 29 Oct 2013 (estimated)
- Results
- Posted 9 Jan 2019
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 determine the relationship between two types of cell signals, type I interferon (IFN) and tumor necrosis factor (TNF), in psoriatic skin prior to and during treatment with etanercept and correlate that information with the degree of the improvement in the psoriasis.
Detailed description
Hypothesis: The balance between type I IFN and TNF determines the response to anti-TNF treatment. The goal of the proposed study is to address this hypothesis and demonstrate that the strength of the type I IFN signature in psoriatic skin is the major determinant of the clinical response to anti-TNF treatment.
Purpose: Determine the strength of the type I interferon and TNF signal in psoriatic skin prior to and during treatment with etanercept and correlate with degree of clinical improvement.
Study Population: up to 50 subjects, men or women over the age of 18 with clinically stable plaque psoriasis, who meet the wash out requirements and other exclusion criteria
Psoriatic patients will receive 100 mg etanercept per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months.
Procedures: Urine pregnancy test, TB test, photography, Physical Examinations, Skin Examinations, Study Drug, Peripheral blood and biopsies
Anticipated Results: We expect that patients with strong IFN-α signature in psoriatic skin along with weak TNF-α signature will have minimal response to anti-TNF treatment, while patients with the opposite pattern, weak IFN and strong TNF signature, will have significant clinical improvement.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Etanercept | Other | Drug: etanercept100 mg Etanercept injections per week for 3 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- At least 18 years of age at screening.
- Clinically stable moderate to severe plaque psoriasis at screening and baseline.
- Subject must be:
- If the subject is sexually active, (s)he must agree to use a medically acceptable form of contraception during screening and throughout the study.
Key exclusion criteria (24 listed)
- Grade 3 or 4 adverse events or infections within 28 days before screening, or between the screening visit and drug initiation.
- Active or chronic infection within 4 weeks before screening visit, or between the screening and baseline visits.
- Evidence of skin conditions other than psoriasis that would interfere with the evaluations of the effect of study medication on psoriasis.
- Use of oral psoralen with ultraviolet A (PUVA), oral retinoids, cyclosporine, alefacept, or any other systemic anti-psoriasis therapy within 28 days study drug initiation.
- Use of ulltraviolet B (UVB) therapy, topical steroids at no higher than moderate strength, topical vitamin A or D analog preparations, or anthralin with 14 days of study initiation.
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 |
|---|---|---|
| etanerceptAlso: ENBREL100 mg Etanercept injections per week (2 separate single-use pre-filled 50 mg subcutaneous injections taken on two separate days) for 3 months | Drug | Etanercept |
Primary outcome
Change in Psoriasis Area and Severity Index (PASI) Score
Time frame: Baseline, 12 weeks
A cumulative change in PASI score from baseline to week 12 will be calculated for each patient. The PASI is the industry standard to decrease/eliminate subjectivity in determining psoriasis severity. It is a quantitative rating scale for measuring the severity of psoriatic lesions based on area coverage and plaque appearance. The severity of plaque characteristics (erythema, thickness and scaling) for body regions (head, upper limbs, trunk and lower limbs) is combined with the degree of plaque involvement in each body region to determine a single PASI score in the range of 0 (no disease) and 72 (maximal disease).
3 secondary outcomes
Tumor Necrosis Factor (TNF)-Alpha Signal Strength
Time frame: Baseline, Week 6, Week 12
Interferon (IFN)-Alpha Signal Strength
Time frame: Baseline, Week 6, Week 12
Psoriasis Area and Severity Index (PASI) Response Profile
Time frame: 12 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Johann Gudjonsson, MD PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing etanercept in people with Psoriasis, run by University of Michigan at 1 site in United States.
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 24 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 4 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 9 Jan 2019). 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?
Change in Psoriasis Area and Severity Index (PASI) Score (time frame: Baseline, 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Mar 2020.