| Purpose: |
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The purpose of this study is to assess the effect of adalimumab (Humira), when compared to
NB-UVB (narrow-band ultraviolet B) phototherapy or placebo (an inactive substance that may
resemble an active substance but has no medical value) injection. The study will compare
the effects of each on systemic inflammation and cardiovascular disease risk factors in
subjects diagnosed with moderate to severe psoriasis.
This study will look for systemic vascular inflammation in subjects with a test called
FDG-PET/CT (Fluorodeoxyglucose-positron emission tomography/computed tomography). The study
will also look for cardio metabolic (heart disease and metabolic factors such as diabetes)
identifiers in the blood. A blood sample will be taken that will look for these markers
identifying high cholesterol, cholesterol efflux function (the ability of cholesterol to
move in the body), metabolic factors, and inflammation.
This study will also assess the effect of adalimumab (Humira), when compared to NB-UVB
phototherapy or placebo injection on psoriasis activity and severity. The study will also
compare the safety of adalimumab (Humira) to NB-UVB phototherapy or placebo injection. This
study will also evaluate subjects reported outcomes through a questionnaire that will assess
quality-of-life in subjects living with psoriasis.
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| Criteria: |
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Inclusion Criteria:
1. Males and females 18 years of age and older.
2. Clinical diagnosis of psoriasis for at least 6 months as determined by subject
interview of his/her medical history and confirmation of diagnosis through physical
examination by Investigator.
3. Stable plaque psoriasis for at least 2 months before Screening and at Baseline (Week
0) as determined by subject interview of his/her medical history.
4. Moderate to severe psoriasis defined by ≥ 10 percent Body Surface Area (BSA)
involvement at the Baseline (Week 0) visit.
5. PASI (psoriasis assessment and severity index) score of ≥ 12 at the Baseline (Week 0)
visit.
6. Subject is a candidate for systemic therapy or phototherapy and has active psoriasis
despite prior treatment with topical agents.
7. Women are eligible to participate in the study if they meet one of the following
criteria:
a. Women of childbearing potential must undergo monthly pregnancy testing during the
study and agree to use two of the following methods of contraception throughout the
6-month study: i. Oral contraceptives; ii. Transdermal contraceptives iii. Injectable
or implantable methods iv. Intrauterine devices v. Barrier methods (for example but
not limited to a diaphragm with spermicide, condom with spermicide); or vi.
Vasectomized partner Subjects using oral or parental forms of contraceptives must
have been practicing birth control for at least three months prior to study drug
administration.
b. Women who are postmenopausal (for at least one year), sterile, or hysterectomized;
c. Women who have undergone tubal ligation will be required to undergo monthly
pregnancy testing during the duration of the study and agree to use a second form of
contraception which includes: i. Oral contraceptives; ii. Transdermal contraceptives
iii. Injectable or implantable methods iv. Intrauterine devices v. Barrier methods
(for example but not limited to a diaphragm with spermicide, condom with spermicide);
or vi. Vasectomized partner d. Sexual abstinence, defined as total abstinence from
sexual intercourse, is considered an adequate form of contraception. (Agreement to
comply with sexual abstinence must be recorded in the source document.)
8. Subject is judged to be in good general health as determined by the Principal
Investigator based upon the results of medical history, laboratory profile, physical
examination, and 12-lead electrocardiogram (ECG) performed at screening.
9. Able and willing to give written informed consent and to comply with requirements of
this study protocol.
Exclusion Criteria:
1. Previous adverse event following exposure to a TNF-alpha antagonist and/or UV
phototherapy that led to discontinuation of either of these therapies and
contraindicates future treatment.
2. Previous lack of response to a TNF-alpha antagonist and/or UV phototherapy that led
to discontinuation of either of these therapies.
3. Diagnosis of erythrodermic psoriasis, generalized or localized pustular psoriasis,
medication-induced or medication-exacerbated psoriasis, or new onset guttate
psoriasis.
4. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or
viral) that may interfere with evaluation of psoriasis.
5. Cannot avoid UVB phototherapy for at least 14 days prior to the Baseline (Week 0)
visit.
6. Cannot avoid psoralen-UVA phototherapy for at least 30 days prior to the Baseline
(Week 0) visit and during the study.
7. Cannot discontinue systemic therapies for the treatment of psoriasis, or systemic
therapies known to improve psoriasis, during the study:
- Systemic (investigational or marketed) therapies must be discontinued at least
30 days prior to the Baseline (Week 0) visit except for biologics.
- All biologics, except ustekinumab, must be discontinued for at least 90
days prior to Baseline (Week 0).
- The IL-12/IL-23 antagonist ustekinumab (half-life of 45.6 ± 80.2 days) must
be discontinued for at least 180 days prior to Baseline (Week 0).
- Investigational agents must be discontinued at least 30 days or 5 half-lives
(whichever is longer) prior to the Baseline (Week 0) visit.
8. Subject is taking or requires oral or injectable corticosteroids during the study.
Inhaled corticosteroids for stable medical conditions are allowed.
9. Poorly controlled medical condition, such as unstable ischemic heart disease,
congestive heart failure, recent cerebrovascular accidents, psychiatric disease
requiring frequent hospitalization, and any other condition, which, in the opinion of
the Investigator, would put the subject at risk by participation in the study.
10. History of diabetes mellitus, type 1 or type 2
11. Uncontrolled hypertension, with measured systolic blood pressure >180 mmHg or
diastolic blood pressure >90 mmHg
12. History of demyelinating diseases or lupus.
13. Subject has infection or risk factors for severe infections, for example:
- Positive serology or known history of HIV, hepatitis B or C, or other severe,
recurrent, or persistent infections;
- Excessive immunosuppression or other factors associated with it, including human
immunodeficiency virus infection;
- Active tuberculosis (TB) disease;
- Evidence of latent TB infection demonstrated by Purified Protein Derivative
(PPD) ≥ 5 mm of induration or positive Quantiferon-GOLD results; except if
prophylactic treatment for TB, as recommended by local guidelines, is initiated
prior to administration of study drug or if there is documentation that the
subject has received prophylactic treatment for TB previously.
- Any other significant infection requiring hospitalization or intravenous (IV)
antibiotics in the month prior to Baseline;
- Infection requiring treatment with oral or parenteral antibiotics within 14 days
prior to Baseline;
- Subject has received vaccination with Bacille Calmette-Guerin (BCG) within 365
days prior to Screening;
- Subject has received vaccination with a live viral agent 30 days prior to
Screening or will require a live vaccination during study participation
including up to 30 days after the last dose of study drug.
14. Subject has history of hematological or solid malignancy other than successfully
treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or
cervical carcinoma in situ.
15. Female subject who is pregnant or breast-feeding or considering becoming pregnant
during the study.
16. Screening clinical laboratory analyses showing any of the following abnormal results:
- Hemoglobin (Hgb) < 10 g/dL in females or <12 g/dL in males;
- White blood cell (WBC) count <2.5 x 109/L
o Subject can be included if WBC count is <2.5 x x 109/L and absolute neutrophil
count (ANC) is >1000 cells / mm3.
- WBC count > 15 x 109/L;
- Platelet count < 100 x 109/L;
- Serum aspartate transaminase (AST) or alanine transaminase (ALT) >2.5 upper
limits of normal (ULN);
- Serum total bilirubin ≥2 mg/dL (≥26 µmol/L); or
- Serum creatinine >1.6 mg/dL (>141 µmol/L).
17. Recent history of substance abuse or psychiatric illness that could preclude
compliance with the protocol.
18. History of any substance abuse within 365 days of screening visit
19. Alcohol use >14 drinks per week at the screening visit or within 30 days of the
screening period
20. If subject is on cholesterol-lowering medication (e.g. statin), dose and form of
medication must be stable for 90 days prior to week 0 and remain stable throughout
the duration of the study.
21. History of photosensitivity of medical condition that may be exacerbated by UV
exposures such as lupus or dermatomyositis
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