Overview

This trial is active, not recruiting.

Condition psoriasis
Treatments ustekinumab, abatacept, placebo for ustekinumab, placebo for abatacept
Phase phase 2
Sponsor National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator Immune Tolerance Network (ITN)
Start date February 2014
End date November 2017
Trial size 108 participants
Trial identifier NCT01999868, DAIT ITN059AI

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
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.
abatacept CTLA4-Ig
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
placebo for ustekinumab Ustekinumab Placebo
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.
(Active Comparator)
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.
ustekinumab anti-IL-12/23
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.
placebo for abatacept Abatacept Placebo
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.

Primary Outcomes

Measure
The proportion of participants who experience a psoriasis relapse at any time between week 12 and week 88
time frame: Week 88

Secondary Outcomes

Measure
The proportion of randomized participants who experience a psoriasis disease relapse prior to week 40
time frame: Week 40
The proportion of participants who experience a psoriasis disease relapse between week 28 and week 88
time frame: Week 88
The proportion of participants who experience a psoriasis disease relapse between week 40 and week 88
time frame: Week 88
Mean length of time after week 12 to psoriasis relapse
time frame: Week 88
Physician's Global Assessment (PGA) of cleared or minimal at week 40 and week 88
time frame: Week 88
Dermatology Life Quality Index (DLQI)
time frame: Weeks 40 and 88
Frequency and severity of all AEs and SAEs
time frame: Week 88

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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

Additional Information

Official title Efficacy of Ustekinumab (Anti-IL-12/23) Followed by Abatacept (CTLA4-Ig) for the Treatment of Psoriasis Vulgaris (ITN059AI)
Principal investigator James Krueger, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by National Institute of Allergy and Infectious Diseases (NIAID).