Diese Seite wurde automatisch übersetzt und die Genauigkeit der Übersetzung wird nicht garantiert. Bitte wende dich an die englische Version für einen Quelltext.

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

26. Dezember 2018 aktualisiert von: 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.

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

108

Phase

  • Phase 2

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

18 Jahre bis 65 Jahre (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Zufällig
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Vervierfachen

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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
Arzneimittel: 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
Aktiver Komparator: 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
Arzneimittel: 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

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse)
Zeitfenster: 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)

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)
Zeitfenster: 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)

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Mitarbeiter

Immune Tolerance Network (ITN)

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Nützliche Links

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

19. März 2014

Primärer Abschluss (Tatsächlich)

7. Dezember 2017

Studienabschluss (Tatsächlich)

1. März 2018

Studienanmeldedaten

Zuerst eingereicht

26. November 2013

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

26. November 2013

Zuerst gepostet (Schätzen)

3. Dezember 2013

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

15. Januar 2019

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

26. Dezember 2018

Zuletzt verifiziert

1. Dezember 2018

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • DAIT ITN059AI

Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .

Klinische Studien zur Schuppenflechte

Klinische Studien zur Ustekinumab

Suchen Sie nach ähnlichen Studien

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

CROs by country

CROs in Uganda

Bedingungen

Seltene Krankheiten

Drogeninterventionen

Nahrungsergänzungsmittel

Sponsor / Mitarbeiter

Standorte

Abonnieren