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

26 december 2018 bijgewerkt door: National Institute of Allergy and Infectious Diseases (NIAID)

Efficacy of Ustekinumab (Anti-IL-12/23) Followed by Abatacept (CTLA4-Ig) for the Treatment of Psoriasis Vulgaris (ITN059AI)

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.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

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.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

108

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2G 1B1
        • Kirk Barber Research
    • Quebec
      • Montreal, Quebec, Canada, H2K 4L5
        • Innovaderm Research Inc.
  • Verenigde Staten
    • California
      • Los Angeles, California, Verenigde Staten, 90045
        • Dermatology Research Associates
    • Illinois
      • Chicago, Illinois, Verenigde Staten, 60611
        • Northwestern University
    • Louisiana
      • New Orleans, Louisiana, Verenigde Staten, 70112
        • Tulane University School of Medicine: Dept. of Dermatology
    • Michigan
      • Ann Arbor, Michigan, Verenigde Staten, 48109
        • University of Michigan
    • New York
      • New York, New York, Verenigde Staten, 10065
        • The Rockefeller University
    • North Carolina
      • Winston-Salem, North Carolina, Verenigde Staten, 27104
        • Wake Forest University
    • Ohio
      • Cleveland, Ohio, Verenigde Staten, 44106
        • Case Western University
    • Utah
      • Salt Lake City, Utah, Verenigde Staten, 84132
        • The University of Utah

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

18 jaar tot 65 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Verviervoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: 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.
Biologisch: 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.

Andere namen:
  • Stelara
  • anti-IL-12/23
Biologisch: 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

Andere namen:
  • Orencia
  • CTLA4-Ig
  • cytotoxic T lymphocyte antigen immunoglobulin fusion protein
Geneesmiddel: 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.
Andere namen:
  • Placebo for Ustekinumab
  • Ustekinumab Placebo
Actieve vergelijker: 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.
Biologisch: 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.

Andere namen:
  • Stelara
  • anti-IL-12/23
Geneesmiddel: 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.
Andere namen:
  • Placebo for Abatacept
  • Abatacept Placebo

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse)
Tijdsspanne: Post-randomization (Week 12 to 88)
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)

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse)
Tijdsspanne: Post-randomization (Week 12 to 88)
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 (Baseline PASI -Week 12 PASI). Participants who terminated early from the study due to reasons other than psoriasis relapse or worsening psoriasis (drop-outs) were considered to have not 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)
Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status)
Tijdsspanne: Post-randomization (Week 12 to 88)
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 (Baseline PASI -Week 12 PASI). Participants who terminated early due to reasons other than psoriasis relapse or worsening psoriasis were considered to have a missing relapse status at time of drop-out and were excluded from the analyses. 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)
Time to Psoriasis Relapse (Treating Drop-Outs as Relapse)
Tijdsspanne: Post-randomization (Week 12 to 88)
Time in weeks from Week 12 to psoriasis relapse. 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)
Time to Psoriasis Relapse (Treating Drop-Outs as Censored)
Tijdsspanne: Post-randomization (Week 12 to 88)
Time in weeks from Week 12 to psoriasis relapse. 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 due to reasons other than psoriasis relapse or worsening psoriasis (drop-outs) were censored at the 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)
Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA)
Tijdsspanne: Week 40, Week 88
Percentage of participants who were classified as cleared or minimal in the Physician's Global Assessment (PGA) average score at the specified post-randomization time point. The PGA assesses the severity of the psoriasis in 3 components: induration, erythema and scaling. Each component is given a score ranging from 0 to 5 based on the majority of the participant's psoriasis lesions, with higher scores indicating worse disease. A PGA average score < 1.5 was classified as "cleared or minimal."
Week 40, Week 88
Change in Dermatology Life Quality Index (DLQI)
Tijdsspanne: Week 40, Week 88
Change in the Dermatology Life Quality Index (DLQI) score from Week 12 to the specified post-randomization time point. DLQI is a 10-question, participant-reported questionnaire that assesses quality of life with respect to skin conditions in the areas of symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment. Each question measures the level of effect that the skin condition has on quality of life, and responses range from 'Not at all' (score = 0) to 'Very much' (score = 3). The overall score is the sum of the scores for all 10 questions and ranges from 0-30, with higher scores indicating worse quality of life.
Week 40, Week 88
Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase)
Tijdsspanne: Lead-In Phase (Week 0 to 12)
Number of participants who experienced adverse events (AEs) during the lead-in phase (Week 0 to 12), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol.
Lead-In Phase (Week 0 to 12)
Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase)
Tijdsspanne: Lead-In Phase (Week 0 to 12)
Number of adverse events (AEs) that occurred during the lead-in phase (Week 0 to 12), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol.
Lead-In Phase (Week 0 to 12)
Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization)
Tijdsspanne: From randomization (Week 12) to last safety follow-up visit (up to Week 100)
Number of participants who experienced adverse events (AEs) during the post-randomization phase (Week 12 to 100), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol. AEs that started prior to randomization but became serious after randomization were included in the counts for the post-randomization time period.
From randomization (Week 12) to last safety follow-up visit (up to Week 100)
Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization)
Tijdsspanne: From randomization (Week 12) to last safety follow-up visit (up to Week 100)
Number of adverse events (AEs) that occurred during the post-randomization phase (Week 12 to 100), classified by severity and type. AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database. In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale. AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol. AEs that started prior to randomization but became serious after randomization were included in the counts for the post-randomization time period.
From randomization (Week 12) to last safety follow-up visit (up to Week 100)

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Medewerkers

Immune Tolerance Network (ITN)

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

19 maart 2014

Primaire voltooiing (Werkelijk)

7 december 2017

Studie voltooiing (Werkelijk)

1 maart 2018

Studieregistratiedata

Eerst ingediend

26 november 2013

Eerst ingediend dat voldeed aan de QC-criteria

26 november 2013

Eerst geplaatst (Schatting)

3 december 2013

Updates van studierecords

Laatste update geplaatst (Werkelijk)

15 januari 2019

Laatste update ingediend die voldeed aan QC-criteria

26 december 2018

Laatst geverifieerd

1 december 2018

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • DAIT ITN059AI

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