Mechanism of Action Study for Psoriasis (MOA)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Tufts Medical Center
ClinicalTrials.gov Identifier:
NCT00932113
First received: June 30, 2009
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

The objective of this study is to compare the mechanism of action between adalimumab and methotrexate in subjects with psoriasis.


Condition Intervention Phase
Psoriasis
Drug: Methotrexate
Drug: Adalimumab (Humira)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Basic Science
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.

Resource links provided by NLM:


Further study details as provided by Tufts Medical Center:

Primary Outcome Measures:
  • Biologic Activity Endpoints: Histologic and Immunohistochemistry endpoints; Relative messenger RNA gene expression (normalized to HARP); and Gene Arrays. [ Time Frame: Weeks 0, 1, 2, 4 and 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical Endpoints for psoriasis: PASI, physician's global assessment (PGA), body surface area (BSA), and Target lesion scoring and photography. [ Time Frame: Weeks 0, 1, 2, 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
  • Safety Outcome Measures: All adverse events (AEs) will be recorded and monitored. [ Time Frame: 16 Weeks ] [ Designated as safety issue: Yes ]
  • Laboratory Assessments: complete blood count (CBC), complete metabolic profile (CMP), c-reactive protein (CRP), antinuclear antibody (ANA), purified protein derivative (PPD), Hepatitis B/C, urine pregnancy test, urinalysis (UA) [ Time Frame: 16 Weeks ] [ Designated as safety issue: Yes ]

Enrollment: 33
Study Start Date: June 2009
Estimated Study Completion Date: June 2014
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Adalimumab
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).
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.
Other Name: Humira
Active Comparator: Methotrexate (MTX)
Patients will be dosed according to the CHAMPION study in single weekly doses of methotrexate: 7.5mg at week 0, 10mg at week two, and 15mg at week 4 for all patients. For each subject if the PASI did not decrease by at least 50% from baseline (PASI-50) at week 8, dosing will be increased to 20mg per week; the dose will be maintained at 15mg per week if PASI-50 was achieved at week 8. If PASI-50 was not achieved at week 12, dosing will be increased to 25mg per week; the dose will be maintained at 20mg per week if the PASI-50 was achieved 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.

Other Names:
  • Methotrexate (MTX)
  • Folic Acid
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.
Other Name: Humira

Detailed Description:

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 tumor necrosis factor blocker) has been reported.

With etanercept, another tumor necrosis factor 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 polymerase chain reaction, and gene arrays.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults 18-85 years of age with moderate to severe psoriasis, in general good health as determined by the PI based upon the results of medical history, laboratory profile, and physical examination, and who are candidates for systemic or phototherapy
  • Presence of a psoriatic plaque of >2cm in an area which can be biopsied repeatedly.
  • Men must agree to avoid impregnating a woman while on this study.
  • Women are eligible to participate in the study if they meet one of the following criteria:

    • Women who are postmenopausal (>1 year), sterile, or hysterectomized
    • Women of childbearing potential must undergo monthly pregnancy testing during the study and agree to use two of the following methods of contraception throughout and for 60 days after the last dose of study drug:

      • Oral contraceptives
      • Transdermal contraceptives
      • Injectable or implantable methods
      • Intrauterine devices
      • Barrier methods (diaphragm or condom with spermicide)
      • Abstinence and Tubal Ligation are also considered a form of Birth control

Exclusion Criteria:

  • Patients <18 or >85 years old
  • Absence of a psoriatic plaque >2cm in diameter
  • Active guttate, erythrodermic, or pustular psoriasis at the time of the screening visit
  • Evidence of skin conditions at screening (e.g. eczema) that would interfere with evaluations of the effect of study medication
  • Inability to understand the consent process
  • Receipt of any investigational drugs, psoralen+ultraviolet A or oral systemic treatments within 4 weeks of study drug initiation
  • Biologics within 3 months of study initiation
  • Topical steroids, topical vitamin A or D analog preparations, Ultraviolet B therapy or anthralin within 2 weeks of study drug initiation. (Exception-stable regimen of class I-II topical steroids on scalp, axillae, and groin)
  • Methotrexate within 6 weeks of study initiation
  • History of treatment with adalimumab
  • History of primary non-response to methotrexate, infliximab or etanercept
  • History of discontinuation of methotrexate or tumor necrosis factor (TNF) blocker for a safety-related reason that makes it unwise to restart either type of drug
  • Any internal malignancy within 5 years (excluding fully excised cutaneous basal cell or squamous cell carcinoma)
  • Pregnancy, not practicing effective birth control, or inability to practice safe sex during the length of the study
  • Lactation
  • Subjects who have known hypersensitivity to adalimumab or methotrexate or any of its components or who is known to have antibodies to etanercept
  • History of alcohol or drug abuse one year before and during the study
  • Known HIV-positive status or any other immune-suppressing disease
  • Presence of a grade 3 or 4 infection <30 days prior to the screening visit, between the screening visit and the first day of treatment on study, or any time during the study that in the opinion of the PI would preclude participation in the study
  • 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 PI would, preclude participation in the study

    • Serum creatinine >3.0 mg/dL (265 micromoles/L)
    • Serum potassium <3.5 mmol/L or > 5.5 mmol/L
    • Serum alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal for the lab
    • Platelet count <100,000/mm3
    • White blood cell count <3,000/mm3
    • Hgb, Hct, or red blood cell outside 30% of the upper or lower limits of normal for the Lab
  • Receipt of live vaccines 1 month prior to or while on study
  • History of tuberculosis, and/or a positive PPD skin test/chest x-ray at screening without appropriate treatment-treatment of latent tuberculosis (for those with positive PPD tests) must be initiated prior to therapy with adalimumab or methotrexate
  • Chronic hepatitis B or C infection, history of multiple sclerosis, transverse myelitis, optic neuritis or epilepsy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00932113

Locations
United States, Massachusetts
Tufts Medical Center, Department of Dermatology
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts Medical Center
Investigators
Principal Investigator: Alice B. Gottlieb, M.D., PhD. Tufts Medical Center, Department of Dermatology
  More Information

Additional Information:
Publications:
Responsible Party: Tufts Medical Center
ClinicalTrials.gov Identifier: NCT00932113     History of Changes
Other Study ID Numbers: MOA, ABT 08-030
Study First Received: June 30, 2009
Last Updated: April 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Tufts Medical Center:
tumor necrosis factor (TNF) inhibitor
tumor necrosis factor (TNF) blockade
Methotrexate
treatment
mechanism
psoriasis

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Methotrexate
Adalimumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on April 17, 2014