Efficacy of Ustekinumab Followed by Abatacept for the Treatment of Psoriasis Vulgaris

NCT ID: NCT01999868

Last Updated: 2019-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-19
• Study Completion Date: 2018-03-01

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.

Conditions

Psoriasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

UST, ABA/UST Placebo

Participants received 2 subcutaneous injections of open-label ustekinumab (UST) (45 mg for participants weighing \<=100 kg at study entry or 90 mg for those weighing \>100 kg at study entry), at Weeks 0 and 4 during the lead-in phase and were then randomized to receive blinded (masked) treatment of abatacept (ABA) (125 mg) subcutaneous injections weekly from Week 12 to 39, in addition to ustekinumab placebo subcutaneous injections at Weeks 16 and 28.

Group Type: EXPERIMENTAL

Ustekinumab

Intervention Type: BIOLOGICAL

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

Intervention Type: BIOLOGICAL

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

UST Placebo

Intervention Type: DRUG

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.

UST, UST/ABA Placebo

Participants received 2 subcutaneous injections of open-label ustekinumab (UST) (45 mg for participants weighing \<=100 kg at study entry or 90 mg for those weighing \>100 kg at study entry), at Weeks 0 and 4 during the lead-in phase and were then randomized to receive blinded (masked) treatment of ustekinumab (45 mg if \<=100 kg or 90 mg if \>100 kg at study entry) subcutaneous injections at Weeks 16 and 28, in addition to abatacept (ABA) placebo subcutaneous injections weekly from Week 12 to 39.

Group Type: ACTIVE_COMPARATOR

Ustekinumab

Intervention Type: BIOLOGICAL

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.

ABA Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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

Intervention Type: BIOLOGICAL

UST 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.

Intervention Type: DRUG

ABA 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.

Intervention Type: DRUG

Other Intervention Names

anti-IL-12/23; Stelara; CTLA4-Ig; cytotoxic T lymphocyte antigen immunoglobulin fusion protein; Orencia; Placebo for Ustekinumab; Ustekinumab Placebo; Placebo for Abatacept; Abatacept Placebo

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Immune Tolerance Network (ITN)

NETWORK

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James Krueger, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The Rockefeller University

Locations

Dermatology Research Associates

Los Angeles, California, United States

Northwestern University

Chicago, Illinois, United States

Tulane University School of Medicine: Dept. of Dermatology

New Orleans, Louisiana, United States

University of Michigan

Ann Arbor, Michigan, United States

The Rockefeller University

New York, New York, United States

Wake Forest University

Winston-Salem, North Carolina, United States

Case Western University

Cleveland, Ohio, United States

The University of Utah

Salt Lake City, Utah, United States

Kirk Barber Research

Calgary, Alberta, Canada

Innovaderm Research Inc.

Montreal, Quebec, Canada

Countries

United States; Canada

References

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.

Reference Type: DERIVED

PMID: 34643650 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID) website

http://www.immunetolerance.org

Immune Tolerance Network (ITN) website

http://www.pausestudy.org/

PAUSE (ITN059AI) ITN Study website

Other Identifiers

DAIT ITN059AI

Identifier Type: -

Identifier Source: org_study_id