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Sponsors and Collaborators: |
Tufts Medical Center Abbott |
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Information provided by: | Tufts Medical Center |
ClinicalTrials.gov Identifier: | NCT00932113 |
The objective of this study is to compare the mechanism of action between adalimumab and methotrexate in subjects with psoriasis.
Condition | Intervention |
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Psoriasis |
Drug: Methotrexate Drug: Adalimumab (Humira) |
Study Type: | Interventional |
Study Design: | Basic Science, Randomized, Single Blind (Outcomes Assessor), Crossover Assignment, Pharmacokinetics/Dynamics Study |
Official Title: | An Investigator-Initiated, Assessor Blinded, Randomized Study Comparing the Mechanism of Action of Adalimumab to Methotrexate in Subjects With Moderate to Severe Chronic Plaque Psoriasis. |
Estimated Enrollment: | 30 |
Study Start Date: | June 2009 |
Estimated Study Completion Date: | September 2010 |
Estimated Primary Completion Date: | June 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Adalimumab: Active Comparator
Dosing will be on day 1 and then weekly. For the injections, dosing will occur according to product recommendations. Patients will receive 80mg adalimumab (2 pre-filled syringes, each with 40mg) on day 1, and then 40mg on week 1 and then every 2 weeks (from week 1 through week 15).
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Drug: Adalimumab (Humira)
2 cohorts (Randomized 1:1 adalimumab:methotrexate). Subjects will receive treatment on Day 1 (baseline visit) and then weekly or every 2 weeks for 16 weeks.
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Methotrexate (MTX): Active Comparator
For oral dosing, patients will be dosed according to the CHAMPION study in single weekly doses of methotrexate: 7.5mg at week 0, increased to 10mg at week two, and increased to 15mg at week 4 for all patients. For oral dosing, if the PASI did not decrease by at least 50% at week 8, dosing will be increased to 20mg per week; the dose will be maintained at 15mg per week if the PASI decreased by 50% or more compared with baseline at week 8. If the PASI did not decrease by at least 50% at week 12, oral dosing will be increased to 25mg per week and will be maintained here; the oral dose will be maintained at 20mg per week if the PASI decreased by 50% or more compared with baseline at week 12. All patients on methotrexate will also receive a dietary supplement of oral folate (5mg per week). Methotrexate-treated patients will then receive 16 weeks of adalimumab at the end of study. |
Drug: Methotrexate
2 cohorts (Randomized 1:1 adalimumab:methotrexate). Subjects will receive treatment on Day 1 (baseline visit) and then weekly or every 2 weeks for 16 weeks. Methotrexate-treated patients will then receive 16 weeks of adalimumab at the end of study.
2 cohorts (Randomized 1:1 adalimumab:methotrexate). Subjects will receive treatment on Day 1 (baseline visit) and then weekly or every 2 weeks for 16 weeks.
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Both methotrexate and adalimumab are FDA-approved drugs for the treatment of moderate to severe psoriasis. The two treatments, methotrexate and adalimumab, both show efficacy for psoriasis, however their profiles differ. In the CHAMPION Study, more adalimumab-treated, moderate to severe psoriasis patients achieved a PASI 75 after 16 weeks compared to those treated with methotrexate (80% vs. 36%). The reason for this difference is poorly understood. No direct comparative mechanism of action studies in psoriasis patients between methotrexate and adalimumab (or any TNF blocker) has been reported.
With etanercept, another TNF blocker, the in vivo mechanism has been studied with some scientific rigor. These studies demonstrate that etanercept down regulates multiple pro-inflammatory pathways (as shown in Table 1 of the protocol).
To date, there are no similar studies with adalimumab or methotrexate.
In order to understand the molecular and cellular basis for the differential clinical efficacy of adalimumab and methotrexate, it is essential to compare their mechanisms of action in psoriatic plaques. Biopsies will be performed, and we will study biomarkers in this proposal with immunohistochemistry, real-time PCR, and gene arrays.
Ages Eligible for Study: | 18 Years to 85 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Women are eligible to participate in the study if they meet one of the following criteria:
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 study and for 60 days after the last dose of study drug:
Exclusion Criteria:
Any grade 3 or 4 adverse event, or laboratory toxicity, at the time of the screening visit or at any time during the study, which in the opinion of the Investigator would, preclude participation in the study
Contact: Nicole Dumont | 617-636-7462 | ndonovan1@tuftsmedicalcenter.org |
Contact: Joseph F. Kerbleski, M.D. | 617-636-7411 | jkerbleski@tuftsmedicalcenter.org |
United States, Massachusetts | |
Tufts Medical Center, Department of Dermatology | Recruiting |
Boston, Massachusetts, United States, 02111 | |
Contact: Nicole Dumont 617-636-7462 ndonovan1@tuftsmedicalcenter.org | |
Contact: Joseph F. Kerbleski, M.D. 617-636-7411 jkerbleski@tuftsmedicalcenter.org | |
Principal Investigator: Alice B. Gottlieb, M.D., PhD | |
Sub-Investigator: Joseph F. Kerbleski, M.D. | |
Sub-Investigator: Katherine Brown, M.D. |
Principal Investigator: | Alice B. Gottlieb, M.D., PhD. | Tufts Medical Center, Department of Dermatology |
Responsible Party: | Tufts Medical Center, Department of Dermatology ( Alice Bendix Gottlieb, MD, PhD ) |
Study ID Numbers: | MOA, ABT 08-030 |
Study First Received: | June 30, 2009 |
Last Updated: | July 1, 2009 |
ClinicalTrials.gov Identifier: | NCT00932113 History of Changes |
Health Authority: | United States: Institutional Review Board |
TNF inhibitor TNF blockade Methotrexate |
treatment mechanism psoriasis |
Antimetabolites Anti-Inflammatory Agents Skin Diseases Immunologic Factors Folate Adalimumab Folic Acid Antagonists Folinic Acid |
Immunosuppressive Agents Vitamin B9 Folic Acid Psoriasis Methotrexate Antirheumatic Agents Skin Diseases, Papulosquamous |
Anti-Inflammatory Agents Antimetabolites Antimetabolites, Antineoplastic Immunologic Factors Molecular Mechanisms of Pharmacological Action Skin Diseases Antineoplastic Agents Physiological Effects of Drugs Enzyme Inhibitors Reproductive Control Agents Folic Acid Antagonists Adalimumab |
Abortifacient Agents, Nonsteroidal Immunosuppressive Agents Pharmacologic Actions Psoriasis Therapeutic Uses Abortifacient Agents Methotrexate Antirheumatic Agents Dermatologic Agents Skin Diseases, Papulosquamous Nucleic Acid Synthesis Inhibitors |