Psoriasis
Conditions
Keywords
Moderate to Severe Chronic plaque type psoriasis
Brief summary
Severe psoriasis has been demonstrated to be associated with decreased endothelial function and an increase risk of future coronary events. Although systemic therapy with immunomodulatory agents has been shown to improve psoriatic symptoms, its effects on systemic inflammation and endothelial function are unknown. In this study we want to assess the cardiovascular risks factors, endothelial dysfunction and inflammatory markers before and after treatment of moderate to severe psoriasis with an FDA-approved biologic agent, adalimumab (Humira).
Interventions
DRUGAdalimumab 40 MG/0.8 ML Subcutaneous Solution [HUMIRA]
40mg subcutaneously, every other week for 6 months
Sponsors
AbbVie
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Must understand and voluntarily sign an informed consent form. * Must be male or female and age 18-55 years at time of consent. * Must be able to adhere to the study visit schedule and other protocol requirements * Have chronic plaque psoriasis for more than 6 months with a PASI score of 12 or greater at Baseline. * Females of childbearing potential (FCBP)‡ must have a negative urine pregnancy test at screening (Visit 1). * Negative PPD at Screening or 3 months earlier. * Have not used any biologic treatment for psoriasis in the past 12 months.
Exclusion criteria
* Inability to provide voluntary consent * Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study * Pregnant, trying to become pregnant or breastfeeding * Prior diagnosis of coronary artery disease (CAD) or heart disease. * Systemic fungal infection * History of past or active mycobacterial infection with any species (including Mycobacterium tuberculosis). Latent Mycobacterium tuberculosis infection as indicated by a positive (more than 15mm induration)Purified Protein Derivative \[PPD\] skin test. Subjects with a positive PPD skin test and documented completion of treatment for latent TB are eligible. Subjects with a positive PPD skin test and not treated or no documentation of completion of treatment are ineligible. * History of recurrent bacterial infection (at least 3 major infections resulting in hospitalization and/or requiring intravenous antibiotic treatment within the past 2 years) * Clinically significant abnormality on the chest x-ray (CXR) at screening. Chest x-rays performed within 3 months prior to start of study drug are acceptable. * Use of any investigational medication within 4 weeks prior to start of study drug or 5 pharmacokinetic/pharmacodynamic half-lives (whichever is longer) * History of Human Immunodeficiency Virus (HIV) infection or Hepatitis C * Positive Hepatitis B Surface antigen at screening * Malignancy or history of malignancy (except for treated \[ie, cured\] basal-cell skin carcinomas \> 3 years prior to screening) * History of any demyelinating disorder such as multiple sclerosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Endothelial Function Compared to Baseline. | 6 months | Percentage change in endothelial function between baseline visit and end of treatment, 6 months. Endothelial function was measured by percent change in brachial artery diameter after flow mediated dilation (FMD%). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in IL-6 Profile Compared to Baseline | 6 months | IL6 average concentration in pg/ml at Baseline compared to end of treatment, 6 months. |
| Changes in Adiponectin Profile Compared to Baseline | 24 weeks | Adiponectin concentration in pg/ml measured at Baseline and end of treatment, 6 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adalimumab active
Adalimumab: 40mg subcutaneously, every other week for 6 months | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Lack of Efficacy | 1 |
Baseline characteristics
| Characteristic | Adalimumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 39 years |
| Gender Female | 6 Participants |
| Gender Male | 12 Participants |
| Region of Enrollment United States | 18 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 5 / 18 |
| serious Total, serious adverse events | 1 / 18 |
Outcome results
Primary
Percentage Change in Endothelial Function Compared to Baseline.
Percentage change in endothelial function between baseline visit and end of treatment, 6 months. Endothelial function was measured by percent change in brachial artery diameter after flow mediated dilation (FMD%).
Time frame: 6 months
Population: 17 of 18 participants completed these assessments at both time points due to one of them having an adverse event that required treatment and therefore end of treatment assessments could not be performed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Adalimumab | Percentage Change in Endothelial Function Compared to Baseline. | -1.414 percent change |
Comparison: Null hypothesis: Percent change in endothelial function from baseline visit to end of treatment/month 6 will be zero change. (percent change=0)p-value: <0.05t-test, 1 sided
Secondary
Changes in Adiponectin Profile Compared to Baseline
Adiponectin concentration in pg/ml measured at Baseline and end of treatment, 6 months.
Time frame: 24 weeks
Population: 17 of 18 participants completed these assessments at both time points due to one of them having an adverse event that required treatment and therefore end of treatment assessments could not be performed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Adalimumab | Changes in Adiponectin Profile Compared to Baseline | 6.125 pg/ml |
Comparison: Null hypothesis: change in adiponectin levels from baseline visit to end of treatment/month 6 will be zero change. (percent change=0)p-value: 0.05t-test, 1 sided
Secondary
Changes in IL-6 Profile Compared to Baseline
IL6 average concentration in pg/ml at Baseline compared to end of treatment, 6 months.
Time frame: 6 months
Population: 17 of 18 participants completed these assessments at both time points due to one of them having an adverse event that required treatment and therefore end of treatment assessments could not be performed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Adalimumab | Changes in IL-6 Profile Compared to Baseline | -0.92 pg/ml |
Comparison: Null hypothesis: change in IL-6 levels from baseline visit to end of treatment/month 6 will be zero change. (percent change=0)p-value: <0.05t-test, 1 sided