Clinical trial NCT01999868: Efficacy of Ustekinumab Followed by Abatacept for the Treatment of Psoriasis Vulgaris
Official title: Efficacy of Ustekinumab (Anti-IL-12/23) Followed by Abatacept (CTLA4-Ig) for the Treatment of Psoriasis Vulgaris (ITN059AI)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Psoriasis
Keywords: psoriasis vulgaris
ustekinumab
abatacept
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Immune Tolerance Network (ITN)
First posted: 2013-12-03
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Psoriasis is a chronic immune disease of the skin and joints that affects about 2% of the population. The most common form of psoriasis is plaque psoriasis, also called psoriasis vulgaris. A variety of drugs, including biologics, are available for treatment of moderate to severe psoriasis. When biologic agents are stopped, psoriasis can return (relapse) and often requires the biologic to be restarted and continued. No treatment program has been identified to prevent relapse of psoriasis.

The study design has a lead-in period of weight-based ustekinumab treatment, with all participants receiving either 45 mg ustekinumab (\<= 100 kg) or 90 mg ustekinumab (\> 100 kg) administered subcutaneously at weeks 0 and 4. At week 12, participants will be assessed for a Psoriasis Area and Severity Index (PASI) 75 response to ustekinumab. Participants who do not achieve a PASI 75 score will be discontinued from the investigation and permitted to seek standard therapy.

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

Primary outcomes:
measure: Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse)
timeFrame: Post-randomization (Week 12 to 88)
Secondary outcomes:
measure: Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse)
timeFrame: Post-randomization (Week 12 to 88)
measure: Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status)
timeFrame: Post-randomization (Week 12 to 88)
measure: Time to Psoriasis Relapse (Treating Drop-Outs as Relapse)
timeFrame: Post-randomization (Week 12 to 88)
measure: Time to Psoriasis Relapse (Treating Drop-Outs as Censored)
timeFrame: Post-randomization (Week 12 to 88)
measure: Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA)
timeFrame: Week 40, Week 88
measure: Change in Dermatology Life Quality Index (DLQI)
timeFrame: Week 40, Week 88
measure: Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase)
timeFrame: Lead-In Phase (Week 0 to 12)
measure: Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase)
timeFrame: Lead-In Phase (Week 0 to 12)
measure: Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization)
timeFrame: From randomization (Week 12) to last safety follow-up visit (up to Week 100)
measure: Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization)
timeFrame: From randomization (Week 12) to last safety follow-up visit (up to Week 100)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Dermatology Research Associates
state: California
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: New Orleans
country: United States
facility: Tulane University School of Medicine: Dept. of Dermatology
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: The Rockefeller University
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western University
state: Ohio
city: Salt Lake City
country: United States
facility: The University of Utah
state: Utah
city: Calgary
country: Canada
facility: Kirk Barber Research
state: Alberta
city: Montreal
country: Canada
facility: Innovaderm Research Inc.
state: Quebec
Study officials:
affiliation: The Rockefeller University
name: James Krueger, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Harris KM, Smilek DE, Byron M, Lim N, Barry WT, McNamara J, Garcet S, Konrad RJ, Stengelin M, Bathala P, Korman NJ, Feldman SR, Boh EE, Barber K, Laumann AE, Helfrich YR, Krueger GG, Sofen H, Bissonnette R, Krueger JG. Effect of Costimulatory Blockade With Abatacept After Ustekinumab Withdrawal in Patients With Moderate to Severe Plaque Psoriasis: The PAUSE Randomized Clinical Trial. JAMA Dermatol. 2021 Nov 1;157(11):1306-1315. doi: 10.1001/jamadermatol.2021.3492.