Mechanism of Action Study for Psoriasis

NCT00932113 | Completed Phase 4 Results

• 2 other identifiers: MOAABT 08-030
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Psoriasis

Keywords

tumor necrosis factor (TNF) inhibitor; tumor necrosis factor (TNF) blockade; Methotrexate; treatment; mechanism; psoriasis

Outcome Measures

Primary Outcomes (1)

• Biologic Activity Endpoints

  Histologic and Immunohistochemistry endpoints; Relative messenger RNA gene expression (normalized to HARP); and Gene Arrays.

  Weeks 0, 1, 2, 4 and 16

Secondary Outcomes (5)

• Clinical Endpoints for Psoriasis: PASI 75

  Weeks 0 and week 16

• Clinical Endpoints for Psoriasis: Physician's Global Assessment (PGA) Clear or Almost Clear (PGA 0-1)

  Week 0 and Week 16

• Clinical Endpoints for Psoriasis: % Body Surface Area

  Week 0 and week 16

• Clinical Endpoints for Psoriasis: Target Lesion Score

  Week 0 and Week 16

• Clinical Endpoints for Psoriasis: Photography Completed

  Week 0 and Week 16

Other Outcomes (1)

• Additional Gene Analysis (Ongoing)

  long-term follow-up visit 4- 6 years post end of study

Study Arms (2)

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).

Drug: Adalimumab (Humira)

Methotrexate (MTX)

ACTIVE COMPARATOR

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; Drug: Adalimumab (Humira)

Interventions

Methotrexate DRUG

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.

Also known as: Methotrexate (MTX), Folic Acid

Methotrexate (MTX)

Adalimumab (Humira) DRUG

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.

Also known as: Humira

Adalimumab; Methotrexate (MTX)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tufts Medical Center: lead

Study Sites (1)

Tufts Medical Center, Department of Dermatology

Boston, Massachusetts, 02111, United States

Location

Related Publications (7)

• Malaviya R, Sun Y, Tan JK, Magliocco M, Gottlieb AB. Induction of lesional and circulating leukocyte apoptosis by infliximab in a patient with moderate to severe psoriasis. J Drugs Dermatol. 2006 Oct;5(9):890-3.

  PMID: 17039656 BACKGROUND

• Malaviya R, Sun Y, Tan JK, Wang A, Magliocco M, Yao M, Krueger JG, Gottlieb AB. Etanercept induces apoptosis of dermal dendritic cells in psoriatic plaques of responding patients. J Am Acad Dermatol. 2006 Oct;55(4):590-7. doi: 10.1016/j.jaad.2006.05.004. Epub 2006 Jul 3.

  PMID: 17010737 BACKGROUND

• Gottlieb AB, Chamian F, Masud S, Cardinale I, Abello MV, Lowes MA, Chen F, Magliocco M, Krueger JG. TNF inhibition rapidly down-regulates multiple proinflammatory pathways in psoriasis plaques. J Immunol. 2005 Aug 15;175(4):2721-9. doi: 10.4049/jimmunol.175.4.2721.

  PMID: 16081850 BACKGROUND

• Tan JK, Aphale A, Malaviya R, Sun Y, Gottlieb AB. Mechanisms of action of etanercept in psoriasis. J Investig Dermatol Symp Proc. 2007 May;12(1):38-45. doi: 10.1038/sj.jidsymp.5650037.

  PMID: 17502868 BACKGROUND

• Lizzul PF, Aphale A, Malaviya R, Sun Y, Masud S, Dombrovskiy V, Gottlieb AB. Differential expression of phosphorylated NF-kappaB/RelA in normal and psoriatic epidermis and downregulation of NF-kappaB in response to treatment with etanercept. J Invest Dermatol. 2005 Jun;124(6):1275-83. doi: 10.1111/j.0022-202X.2005.23735.x.

  PMID: 15955104 BACKGROUND

• Saurat JH, Stingl G, Dubertret L, Papp K, Langley RG, Ortonne JP, Unnebrink K, Kaul M, Camez A; CHAMPION Study Investigators. Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION). Br J Dermatol. 2008 Mar;158(3):558-66. doi: 10.1111/j.1365-2133.2007.08315.x. Epub 2007 Nov 28.

  PMID: 18047523 RESULT

• Goldminz AM, Suarez-Farinas M, Wang AC, Dumont N, Krueger JG, Gottlieb AB. CCL20 and IL22 Messenger RNA Expression After Adalimumab vs Methotrexate Treatment of Psoriasis: A Randomized Clinical Trial. JAMA Dermatol. 2015 Aug;151(8):837-46. doi: 10.1001/jamadermatol.2015.0452.

  PMID: 25946554 DERIVED

MeSH Terms

Conditions

Psoriasis

Interventions

Methotrexate; Folic Acid; Adalimumab

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Nicole Dumont
• Organization: Tufts Medical Center

ndonovan1@tuftsmedicalcenter.org

617 636 7462

Study Officials

• Alice B. Gottlieb, M.D., PhD.

  Tufts Medical Center, Department of Dermatology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: June 30, 2009
• First Posted: July 3, 2009
• Study Start: June 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: May 1, 2017
• Last Updated: August 31, 2017
• Results First Posted: July 2, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)