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

NCT01999868 | Completed Phase 2 Results DMC

• 1 other identifier: DAIT ITN059AI
• Study Type: interventional
• Target: 108
• Locations: 2 countries
• Sites: 10

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.

Conditions

Psoriasis

Keywords

psoriasis vulgaris; ustekinumab; abatacept

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse)

  The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12. This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is ≥ Week 12 PASI + \[(Baseline PASI -Week 12 PASI)/2\]). Participants who terminated early from the study (drop-outs) were considered to have experienced relapse at time of drop-out. PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities. Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4). Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score. The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).

  Post-randomization (Week 12 to 88)

Secondary Outcomes (10)

• Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse)

  Post-randomization (Week 12 to 88)

• Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status)

  Post-randomization (Week 12 to 88)

• Time to Psoriasis Relapse (Treating Drop-Outs as Relapse)

  Post-randomization (Week 12 to 88)

• Time to Psoriasis Relapse (Treating Drop-Outs as Censored)

  Post-randomization (Week 12 to 88)

• Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA)

  Week 40, Week 88

Study Arms (2)

UST, ABA/UST Placebo

EXPERIMENTAL

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.

Biological: Ustekinumab; Biological: Abatacept; Drug: UST Placebo

UST, UST/ABA Placebo

ACTIVE COMPARATOR

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.

Biological: Ustekinumab; Drug: ABA Placebo

Interventions

Ustekinumab 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.

Also known as: anti-IL-12/23, Stelara

UST, ABA/UST Placebo; UST, UST/ABA Placebo

Abatacept 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

Also known as: CTLA4-Ig, cytotoxic T lymphocyte antigen immunoglobulin fusion protein, Orencia

UST, ABA/UST Placebo

UST Placebo 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.

Also known as: Placebo for Ustekinumab, Ustekinumab Placebo

UST, ABA/UST Placebo

ABA Placebo 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.

Also known as: Placebo for Abatacept, Abatacept Placebo

UST, UST/ABA Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Immune Tolerance Network (ITN): collaborator

Study Sites (10)

Dermatology Research Associates

Los Angeles, California, 90045, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Tulane University School of Medicine: Dept. of Dermatology

New Orleans, Louisiana, 70112, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

The Rockefeller University

New York, New York, 10065, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27104, United States

Location

Case Western University

Cleveland, Ohio, 44106, United States

Location

The University of Utah

Salt Lake City, Utah, 84132, United States

Location

Kirk Barber Research

Calgary, Alberta, T2G 1B1, Canada

Location

Innovaderm Research Inc.

Montreal, Quebec, H2K 4L5, Canada

Location

Related Publications (1)

• 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.

  PMID: 34643650 DERIVED

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Immune Tolerance Network (ITN) website
• PAUSE (ITN059AI) ITN Study website

MeSH Terms

Conditions

Psoriasis

Interventions

Ustekinumab; Abatacept

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoconjugates

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• James Krueger, MD, PhD

  The Rockefeller University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2013
• First Posted: December 3, 2013
• Study Start: March 19, 2014
• Primary Completion: December 7, 2017
• Study Completion: March 1, 2018
• Last Updated: January 15, 2019
• Results First Posted: December 26, 2018

Record last verified: 2018-12

Locations

US (8); CA (2)