Efficacy of Ustekinumab Followed by Abatacept for the Treatment of Psoriasis Vulgaris
Condition: Psoriasis
MeSH terms: Psoriasis
Intervention: Ustekinumab; Abatacept; UST Placebo; ABA Placebo
Intervention description: Ustekinumab interferes with the actions of proteins, interleukin 12 (IL12) and interleukin 23 (IL23), which reduces inflammation (swelling) in the skin. Stelara™ is the trade name for ustekinumab and is approved by the U.S. Food and Drug Administration (FDA) to treat psoriasis.
Dose:
Participants who weigh <= 100 kg at study entry will receive 45 mg of ustekinumab.
Participants who weigh > 100 kg at study entry will receive 90 mg of ustekinumab.; Abatacept (one form of the protein called CTLA4-Ig) interacts with the immune system, reducing the activity of T-cells and may prevent relapse. Orencia™ is the trade name for abatacept, and it is approved by the FDA to treat rheumatoid arthritis in adults.
Dose:
125 mg sub-cutaneous injection; The abatacept treatment group will also receive subcutaneous placebo for ustekinumab (sterile normal saline) at week 16 and week 28, corresponding to the ustekinumab dosing regimen.; The ustekinumab treatment group will also receive weekly subcutaneous injections of placebo for abatacept from week 12 to week 39, corresponding to the abatacept dosing regimen.
Intervention MeSH terms: Abatacept; Ustekinumab; Immunoglobulins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 108.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: psoriasis vulgaris; ustekinumab; abatacept

Summary:

      The purpose of this study is to determine if the use of ustekinumab, followed by abatacept,
      will prevent relapse in people with moderate to severe plaque psoriasis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A diagnosis of plaque psoriasis for at least 6 months

          -  Baseline Psoriasis Area and Severity Index (PASI) score >= 12

          -  >=10% body surface area psoriasis involvement

          -  Willingness to forgo other available psoriasis therapies, live vaccines, and pregnancy
             during the trial

          -  Ability and willingness to provide informed consent and comply with study requirements

        Exclusion Criteria:

          -  Non-plaque forms of psoriasis

          -  Grade 2 or 3 moderate to severe psoriatic arthritis not adequately managed with
             non-steroidal anti-inflammatory drugs (NSAIDs)

          -  Myocardial infarction, unstable angina, cerebrovascular accident, or other significant
             cardiovascular event within the previous one year

          -  Chronic obstructive pulmonary disease (COPD)

          -  Comorbid condition that requires regular systemic corticosteroid treatment

          -  History of malignancy, except treated basal cell skin carcinoma

          -  Treated basal cell skin carcinoma within the previous 5 years

          -  Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal,
             pulmonary, cardiac, or neurological disease, or any other medical condition that, in
             the investigator's opinion, places the participant at risk by participating in this
             study

          -  History of recent or ongoing uncontrolled bacterial, viral, fungal, or other
             opportunistic infections

          -  Evidence of infection with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human
             Immunodeficiency Virus (HIV)

          -  Positive QuantiFERON-TB Gold test. Purified Protein Derivative (PPD) tuberculin test
             may be substituted for QuantiFERON-TB Gold test.

          -  Severe reaction or anaphylaxis to any human monoclonal antibody

          -  Any previous treatment with agents targeting Interleukin (IL)-12 or IL-23, including
             ustekinumab

          -  Any previous treatment with abatacept

          -  Treatment with biologic agents within previous 3 months, including adalimumab,
             etanercept, and infliximab

          -  Treatment with immunosuppressive medications, including methotrexate, cyclosporine,
             oral retinoids, prednisone, or phototherapy within previous 4 weeks

          -  Topical psoriasis treatment within previous 2 weeks, including topical
             corticosteroids, vitamin D analogues, retinoids, calcineurin inhibitors, salicylic
             acid, and coal tar

          -  Investigational study medication within previous 6 months

          -  Liver function test (aspartate aminotransferase [AST], alanine aminotransferase [ALT],
             or alkaline phosphatase) results that are >/= 2x the upper limit of normal (ULN).

          -  Serum creatinine >= 2x the ULN.

          -  Any of the following hematologic abnormalities, confirmed by repeat test at least 1
             week apart:

               1. White blood count <3,000/μL or >14,000/μL;

               2. Lymphocyte count <1,000/μL;

               3. Neutrophil count <1,500/μL;

               4. Platelet count <150,000 /μL; or

               5. Hemoglobin <10 g/dL.

          -  Females who are pregnant, lactating, planning on pregnancy during the study period, or
             unwilling to use FDA-approved method of birth control

          -  Receipt of a live vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated
             intranasal influenza vaccine, and smallpox) in the 6 weeks before enrollment

          -  BCG (Bacillus Calmette-Guérin) vaccine one year prior to enrollment