MAP Study: Methotrexate and Adalimumab in Psoriasis (MAP)

MAP Study (Methotrexate and Adalimumab in Psoriasis): Adalimumab vs. Combination Adalimumab and Methotrexate in Psoriasis: Efficacy and Anti-Adalimumab Antibody Formation

Assess the efficacy and safety of ADA compared to ADA/MTX in patient with Psoriasis. Compare Anti-ADA antibody formation and serum ADA levels in patients on ADA compared with those on combination ADA and MTX.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Placebo; Biological: Adalimumab; Drug: Methotrexate

Detailed Description

Assess the efficacy and safety of ADA compared to ADA/MTX in patients with psoriasis. Many studies of ADA in rheumatoid and psoriatic arthritis have allowed patients on stable doses of MTX to continue on MTX while being treated with ADA. There has been no prospective trial of MTX and ADA concomitantly in psoriasis. Safety of ADA monotherapy vs. combination ADA/MTX will be compared.

Compare anti-ADA antibody formation and serum ADA levels in patients on ADA compared with those on combination ADA and MTX. ADA is a fully human monoclonal antibody to TNF-a. More recent advances in detection of ADA antibodies have shown that many patients develop antibodies to ADA while on treatment and some of these antibodies are neutralizing. The presence of anti-ADA antibodies has been correlated with loss of therapeutic response in many disease states.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Bakersfield, California, United States, 93309
      • Bakersfield Dermatology and Skin Cancer Medical Group
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute
  • Maryland
    • Rockville, Maryland, United States, 20850
      • DermAssociates, PC
  • Texas
    • Dallas, Texas, United States, 75231
      • Modern Research Associates, PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female adult (≥ 18yrs) with a diagnosis of moderate to severe plaque psoriasis
2. Subject must have ≥ 10% body surface area involvement
3. Subject must have psoriasis area and severity index (PASI) ≥12
4. Subject has stable psoriasis of at least six months' duration

5. Male subjects must agree to use a reliable form of birth control during the study and for 180 days after the last dose of study drug. Male subjects must not donate sperm during the study or for 180 days after the last dose of study drug. If female, subject is either not of childbearing potential (postmenopausal for at least 1 year or surgically sterile) or is of childbearing potential and is using approved method of birth control throughout study and for 180 days after last dose of study drug. Approved methods of birth control include the following:

   1. Condoms, sponge, foams, jellies, diaphragm, or intrauterine device (IUD)
   2. Hormonal contraceptives for 90 days prior to study drug administration
   3. A vasectomized partner
6. Subject has negative PPD tuberculosis skin test at screening assessment.
7. Subject must be able and willing to provide written informed consent and comply with requirements of this study protocol.

Exclusion Criteria

1. Diagnosis or presence of guttate, erythrodermic or pustular psoriasis
2. Any previous exposure to ADA including biosimilar ADA
3. Moderate to high strength topical steroids (class 4 or greater) or Vitamin D analogues within one week of study entry
4. Oral systemic therapy (methotrexate, cyclosporine, apremilast, acitretin) within 8 weeks of study entry
5. Previous intolerance or adverse reaction to MTX
6. Phototherapy of any type within 4 weeks of study entry (narrowband UVB, psoralen-UVA, 308 nM LASER, commercial tanning units)
7. IL-12/23 inhibitors (ustekinumab) and any IL-23 inhibitor (guselkumab, tildrakizumab, risankizumab) within 12 weeks of baseline
8. Other biologic agents within 8 weeks of study entry
9. History of chronic liver disease, hepatitis, or alcohol abuse
10. Chronic use of any concomitant medication which has a significant potential for interaction with MTX (e.g. sulfa antibiotics, chronic non-steroidal anti-inflammatory (NSAID) use)
11. History of tuberculosis, opportunistic infections, or any active infection at screening
12. Elevated liver enzymes (AST, ALT, ≥1.5 times normal at screening)
13. Serum creatinine ≥1.5 (at screening)
14. Any other laboratory abnormality that would pose a concern for the investigator
15. Daily alcohol use or consumption of more than four alcoholic drinks (4 ounces) in one 24 hour period
16. Patients who test positive for hepatitis B or C exposure (previous vaccination to Hepatitis B is allowed)
17. Cancer within the last five years is exclusionary with the exception of treated cutaneous basal cell carcinoma or squamous cell carcinoma or low-grade cervical intraepithelial neoplasia.
18. Any patient that is deemed by the investigator to be at a safety risk for the intervention in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: ADA and Placebo; Adalimumab 40 mg, Subcutaneous, Bi-Weekly, 16 Weeks Placebo, Tablet, Oral, Weekly, 16 Weeks	Drug: Placebo; Oral Tablet; Biological: Adalimumab; Subcutaneous Injection; Other Names: Humira
Active Comparator: ADA and MTX; Adalimumab 40 mg, Subcutaneous, Bi-Weekly, 16 Weeks Methotrexate, 2.5 mg Tablet, 10 mg Weekly, Oral, 16 Weeks	Biological: Adalimumab; Subcutaneous Injection; Other Names: Humira; Drug: Methotrexate; Oral Tablet; Other Names: MTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PASI Change	Mean percent change in PASI from 16 Weeks to Baseline	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADA/Anti ADA Antibodies	Antibodies to Adalimumab at 16 weeks	16 weeks

Collaborators and Investigators

• Sponsor: Jeffrey J Crowley MD
• Collaborators: AbbVie
• Investigators: Study Director: Jeffrey J Crowley, MD, Bakersfield Dermatology and Skin Cancer Medical Group

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2017
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2018

Study Registration Dates

• First Submitted: July 12, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): July 9, 2019
• Last Update Submitted That Met QC Criteria: July 8, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Adalimumab; Methotrexate
• Other Study ID Numbers: A16-241

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes