MAP Study: Methotrexate and Adalimumab in Psoriasis

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Psoriasis

Intervention / Treatment
-----------------
* Biological: Adalimumab
* Drug: Methotrexate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female adult (≥ 18yrs) with a diagnosis of moderate to severe plaque psoriasis Subject must have ≥ 10% body surface area involvement Subject must have psoriasis area and severity index (PASI) ≥12 Subject has stable psoriasis of at least six months' duration 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: Condoms, sponge, foams, jellies, diaphragm, or intrauterine device (IUD) Hormonal contraceptives for 90 days prior to study drug administration A vasectomized partner Subject has negative PPD tuberculosis skin test at screening assessment. Subject must be able and willing to provide written informed consent and comply with requirements of this study protocol. Exclusion Criteria Diagnosis or presence of guttate, erythrodermic or pustular psoriasis Any previous exposure to ADA including biosimilar ADA Moderate to high strength topical steroids (class 4 or greater) or Vitamin D analogues within one week of study entry Oral systemic therapy (methotrexate, cyclosporine, apremilast, acitretin) within 8 weeks of study entry Previous intolerance or adverse reaction to MTX Phototherapy of any type within 4 weeks of study entry (narrowband UVB, psoralen-UVA, 308 nM LASER, commercial tanning units) IL-12/23 inhibitors (ustekinumab) and any IL-23 inhibitor (guselkumab, tildrakizumab, risankizumab) within 12 weeks of baseline Other biologic agents within 8 weeks of study entry History of chronic liver disease, hepatitis, or alcohol abuse 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) History of tuberculosis, opportunistic infections, or any active infection at screening Elevated liver enzymes (AST, ALT, ≥1.5 times normal at screening) Serum creatinine ≥1.5 (at screening) Any other laboratory abnormality that would pose a concern for the investigator Daily alcohol use or consumption of more than four alcoholic drinks (4 ounces) in one 24 hour period Patients who test positive for hepatitis B or C exposure (previous vaccination to Hepatitis B is allowed) 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. Any patient that is deemed by the investigator to be at a safety risk for the intervention in this trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

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