ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy of Ustekinumab Followed by Abatacept for the Treatment of Psoriasis Vulgaris (PAUSE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01999868
Recruitment Status : Completed
First Posted : December 3, 2013
Last Update Posted : March 21, 2018
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease Intervention/treatment Phase
Psoriasis Biological: Ustekinumab Biological: Abatacept Procedure: Placebo for Ustekinumab Drug: Placebo for Abatacept Phase 2

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Efficacy of Ustekinumab (Anti-IL-12/23) Followed by Abatacept (CTLA4-Ig) for the Treatment of Psoriasis Vulgaris (ITN059AI)
Actual Study Start Date : March 19, 2014
Actual Primary Completion Date : December 7, 2017
Actual Study Completion Date : March 1, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis

Arm Intervention/treatment
Experimental: Abatacept After Removal of Ustekinumab
Subjects in this arm receive abatacept subcutaneous injections of 125 mg, from week 12 to week 39. The abatacept treatment group will also receive subcutaneous ustekinumab placebo at week 16 and week 28, corresponding to the ustekinumab dosing regimen.
Biological: Abatacept

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

Other Names:
  • CTLA4-Ig
  • cytotoxic T lymphocyte antigen immunoglobulin fusion protein
  • Orencia

Procedure: Placebo for Ustekinumab
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.
Other Name: Ustekinumab Placebo

Active Comparator: Continued Ustekinumab
The continued ustekinumab treatment group will receive subcutaneous injections of 45 mg ustekinumab (<= 100 kg) or 90 mg ustekinumab (> 100 kg) at week 16 and week 28. The ustekinumab treatment group will also receive weekly subcutaneous injections of abatacept placebo from week 12 to week 39, corresponding to the abatacept dosing regimen.
Biological: Ustekinumab

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.

Other Names:
  • anti-IL-12/23
  • Stelara

Drug: Placebo for Abatacept
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.
Other Name: Abatacept Placebo




Primary Outcome Measures :
  1. The proportion of participants who experience a psoriasis relapse at any time between week 12 and week 88 [ Time Frame: Week 88 ]
    Psoriasis relapse is defined as loss of >= 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at week 12. The primary endpoint will be assessed in all randomized participants.


Secondary Outcome Measures :
  1. The proportion of randomized participants who experience a psoriasis disease relapse prior to week 40 [ Time Frame: Week 40 ]
  2. The proportion of participants who experience a psoriasis disease relapse between week 28 and week 88 [ Time Frame: Week 88 ]
  3. The proportion of participants who experience a psoriasis disease relapse between week 40 and week 88 [ Time Frame: Week 88 ]
  4. Mean length of time after week 12 to psoriasis relapse [ Time Frame: Week 88 ]
  5. Physician's Global Assessment (PGA) of cleared or minimal at week 40 and week 88 [ Time Frame: Week 88 ]
  6. Dermatology Life Quality Index (DLQI) [ Time Frame: Weeks 40 and 88 ]
  7. Frequency and severity of all AEs and SAEs [ Time Frame: Week 88 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01999868


Locations
United States, California
Dermatology Research Associates
Los Angeles, California, United States, 90045
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Louisiana
Tulane University School of Medicine: Dept. of Dermatology
New Orleans, Louisiana, United States, 70112
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, New York
The Rockefeller University
New York, New York, United States, 10065
United States, North Carolina
Wake Forest University
Winston-Salem, North Carolina, United States, 27104
United States, Ohio
Case Western University
Cleveland, Ohio, United States, 44106
United States, Utah
The University of Utah
Salt Lake City, Utah, United States, 84132
Canada, Alberta
Kirk Barber Research
Calgary, Alberta, Canada, T2G 1B1
Canada, Quebec
Innovaderm Research Inc.
Montreal, Quebec, Canada, H2K 4L5
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Immune Tolerance Network (ITN)
Investigators
Principal Investigator: James Krueger, MD, PhD The Rockefeller University

Additional Information:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01999868     History of Changes
Other Study ID Numbers: DAIT ITN059AI
First Posted: December 3, 2013    Key Record Dates
Last Update Posted: March 21, 2018
Last Verified: March 2018

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
psoriasis vulgaris
ustekinumab
abatacept

Additional relevant MeSH terms:
Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Immunoglobulins
Abatacept
Ustekinumab
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Dermatologic Agents