Effect of Adalimumab on Vascular Inflammation in Patients With Moderate to Severe Plaque Psoriasis

NCT00940862 | Completed Phase 4

• 1 other identifier: Inno-6009
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

This study is to determine the effect of adalimumab on inflammation of blood vessels that could lead to heart attack in patients with psoriasis. Changes to the carotid artery and ascending aorta will be evaluated in patients treated with adalimumab (systemic treatment) and compared against patients treated with a topical treatment that does not affect the entire body.

Conditions

Psoriasis; Vascular Inflammation; Coronary Atherosclerosis

Keywords

psoriasis; vascular inflammation; coronary atherosclerosis

Outcome Measures

Primary Outcomes (1)

• The changes in the target (atherosclerotic plaque) to background (blood) ratio (TBR) from the carotid artery and ascending aorta in patients randomized to adalimumab as compared to patients randomized to standard non-systemic therapy.

  Day -10 to -1, Day 105

Secondary Outcomes (4)

• The changes in the TBR from a coronary artery from Day 0 to Day 105 in patients randomized to adalimumab as compared to patients randomized to standard therapy.

  Day -10 to -1, Day 105.

• To study changes in hs C-Reactive protein levels and serum lipids levels between Day 0 and Day 112 in patients randomized to adalimumab compared to patients randomized to standard therapy.

  Day 0, 28, 56, 112

• To study the safety of adalimumab in patients with psoriasis and history of coronary atherosclerosis or with at least three risk factors for coronary atherosclerosis. atherosclerosis or with at least three risk factors for coronary atherosclerosis

  Day 0, 28, 56, 112, 175

• To study the efficacy of adalimumab in patients with psoriasis and coronary atherosclerosis or at least three risk factors. PASI will be recorded and the percentage of patients achieving PASI 75 at Day 112 will be calculated for all patients randomized.

  Day 0, 28, 56, 112

Study Arms (2)

adalimumab

EXPERIMENTAL

A total of 20 patients will be randomized to adalimumab (80 mg followed by 40 mg at week 1 and 40 mg EOW thereafter for 15 weeks)

Biological: adalimumab

Non-systemic treatment.

ACTIVE COMPARATOR

A total of 10 patients will be randomized to non systemic therapy for psoriasis (topical treatments and/or UVB phototherapy).

Device: UVB Phototherapy; Other: Topical treatment

Interventions

adalimumab BIOLOGICAL

Injection of adalimumab (80 mg followed by 40 mg at week 1 and 40 mg EOW thereafter for 15 weeks)

Also known as: Humira

adalimumab

UVB Phototherapy DEVICE

This intervention can be applied alone or in combination with topical treatment. It will be performed between Day 0 and Day 112. The investigator is free to introduce or modify the topical and/or UVB regimens at any time after screening.

Also known as: Ultra violet light B

Non-systemic treatment.

Topical treatment OTHER

This intervention can be applied alone or in combination with UVB phototherapy. It will be performed between Day 0 and Day 112. The investigator is free to introduce or modify the topical and/or UVB regimens at any time after screening. The investigator will prescribe to patients randomized in this arm a select topical product from the list: Calcipotriol, Calcipotriene, Dovonex, Tazorac, Tazarotene Anthralin, Corticosteroids.

Non-systemic treatment.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years old and capable of giving informed consent.
• at least a 6-month history of chronic moderate to severe psoriasis and a candidate for systemic therapy.
• BSA covered with psoriasis of at least 5 % or more at Baseline.
• An history of coronary atherosclerosis or at least three risk factors among the following: hypertension, active smoking, diabetes mellitus, dyslipidemia, obesity, microalbuminuria, age above 55 years, and first degree relative with coronary atherosclerosis before 65 years.
• Patient must be on a stable dose for at least 8 weeks before baseline if taking medications used to control angina, hypertension, serum lipids and any medication that can have an effect on inflammation.
• Patient has a carotid or ascending aorta atherosclerotic plaque inflammation target-to background ratio of 1.6 or more as determined by 18-FDG uptake measured by PET scanning.
• Female patient is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practicing one of the following methods of birth control throughout the study and for 150 days after study completion:
• condoms, sponge, foams, jellies, diaphragm or IUD.
• contraceptives for three months prior to study drug administration
• a vasectomized partner.
• Female patient of childbearing potential must have a negative serum pregnancy test at the Screening visit.
• Patient is judged to be in good general health as determined by the principal investigator.
• Patient will be evaluated for latent TB infection with a PPD or a Quantiferon Gold test and CXR. Patient who demonstrates evidence of latent TB infection will only be allowed to participate in the study if they are willing to use TB prophylaxis according to Canadian guidelines
• Patient must be able and willing to provide written informed consent and comply with the requirements of this study protocol.
• Patient must be able and willing to self-administer SC injections or have a qualified person available to administer SC injections.

You may not qualify if:

• Patient has other active skin diseases or skin infections (that may interfere with evaluation of psoriasis or with patient's safety.
• Patient has a history of an allergic reaction or significant sensitivity to constituents of study drug, including latex.
• Patient used any non-biological systemic therapy for the treatment of psoriasis less than 30 days before Day 0. Investigational chemical agents must be discontinued at least 30 days or five half-lives prior to the Baseline visit (whichever is longer).
• Patient who has used any biological therapy for the treatment of psoriasis less than 3 months (90 days) before Day 0.
• Patient is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
• Patient has used any topical treatment for psoriasis or has used phototherapy within the last 2 weeks prior to baseline (at the exception of low strength (hydrocortisone and desonide) topical corticosteroid for the face, groin (including genitals) and inframammary areas).
• Patient has received Anakinra/Kineret within the last 2 weeks prior to the Baseline visit or is likely to receive Anakinra/Kineret during the course of the study.
• Patient has a poorly controlled medical condition, such as uncontrolled diabetes, documented history of recurrent infections, unstable ischemic heart disease, congestive heart failure a left ventricular ejection fraction of less than 40%, recent stroke, chronic leg ulcer or any other condition which, in the opinion of the investigator, would put the patient at risk if participating in the study.
• Patient had a myocardial infarction or hospitalization for a cardiac condition within the past 12 weeks.
• Patient has a history of acute coronary syndrome, percutaneous coronary intervention, coronary artery bypass graft, or carotid revascularization within 12 weeks of baseline.
• Patient for whom a change in medical treatment for angina, serum lipids, hypertension or any other medication that can have a significant effect on inflammation is planned for the duration of the study.
• Patient has a history of neurologic symptoms suggestive of central nervous system demyelinating disease.
• Patient has history of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix.
• Patient has a history of listeriosis, treated or untreated TB, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous anti-infectives within 30 days or oral anti-infectives within 14 days prior to the Baseline visit.
• Patient has received any live attenuated vaccine 28 days or less before baseline.

Sponsors & Collaborators

• Innovaderm Research Inc.: lead
• Abbott: collaborator
• Montreal Heart Institute: collaborator

Study Sites (2)

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

Innovaderm Research Inc

Montreal, Quebec, H2K 4L5, Canada

Location

Related Publications (27)

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• Gelfand JM, Feldman SR, Stern RS, Thomas J, Rolstad T, Margolis DJ. Determinants of quality of life in patients with psoriasis: a study from the US population. J Am Acad Dermatol. 2004 Nov;51(5):704-8. doi: 10.1016/j.jaad.2004.04.014.

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• Weiss SC, Kimball AB, Liewehr DJ, Blauvelt A, Turner ML, Emanuel EJ. Quantifying the harmful effect of psoriasis on health-related quality of life. J Am Acad Dermatol. 2002 Oct;47(4):512-8. doi: 10.1067/mjd.2002.122755.

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• Tremblay JF, Bissonnette R. Topical agents for the treatment of psoriasis, past, present and future. J Cutan Med Surg. 2002 May-Jun;6(3 Suppl):8-11. doi: 10.1177/12034754020060S303. Epub 2002 Apr 30. No abstract available.

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• Guenther L, Langley RG, Shear NH, Bissonnette R, Ho V, Lynde C, Murray E, Papp K, Poulin Y, Zip C. Integrating biologic agents into management of moderate-to-severe psoriasis: a consensus of the Canadian Psoriasis Expert Panel. February 27, 2004. J Cutan Med Surg. 2004 Sep-Oct;8(5):321-37. doi: 10.1007/s10227-005-0035-1.

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• Langley RG, Ho V, Lynde C, Papp KA, Poulin Y, Shear N, Toole J, Zip C. Recommendations for incorporating biologicals into management of moderate to severe plaque psoriasis: individualized patient approaches. J Cutan Med Surg. 2006;9 Suppl 1:18-25. doi: 10.1007/s10227-006-0103-1.

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• Bissonnette R, Tardif JC, Harel F, Pressacco J, Bolduc C, Guertin MC. Effects of the tumor necrosis factor-alpha antagonist adalimumab on arterial inflammation assessed by positron emission tomography in patients with psoriasis: results of a randomized controlled trial. Circ Cardiovasc Imaging. 2013 Jan 1;6(1):83-90. doi: 10.1161/CIRCIMAGING.112.975730. Epub 2012 Nov 30.

  PMID: 23204039 DERIVED

MeSH Terms

Conditions

Psoriasis; Coronary Artery Disease

Interventions

Adalimumab; Therapeutics

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Robert Bissonnette, MD

  Innovaderm Research

  PRINCIPAL INVESTIGATOR

• Jean-Claude Tardif, MD, FRCPC

  Montreal Heart Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2009
• First Posted: July 16, 2009
• Study Start: July 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: August 1, 2011
• Last Updated: October 28, 2011

Record last verified: 2011-10

Locations

CA (2)