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Long-Term Effects of Infliximab in the Treatment of Moderate to Severe Psoriasis [Extension of Study P04271, NCT00251641] (P04563)

Primary Purpose

Psoriasis

Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
infliximab
infliximab
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Psoriasis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Subjects must have met all inclusion/exclusion criteria in Study P04271 (NCT00251641). Subjects must have been originally randomized to infliximab in Study P04271. Subjects must have completed the full 26 weeks of Study P04271. Subjects must have remained on infliximab for the full 22 weeks of treatment in Study P04271. Subjects must have achieved an improvement in Psoriasis Area and Severity Index (PASI) score >=75% from Baseline of Study P04271 to Week 26 of Study P04271. Subjects must agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during the study. Subjects are considered eligible according to the following tuberculosis (TB) criteria: Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination; Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study medication. Subjects' Baseline (Visit 1) clinical laboratory tests (complete blood count, blood chemistry, and urinalysis) must be within the following parameters: Hemoglobin >=10 g/dL White blood cells >=3.5 x 10^9/L Neutrophils >=1.5 x 10^9/L Platelets >=100 x 10^9/L Serum creatinine <1.5 mg/dL (or <133 umol/L) Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase levels as outlined in Protocol P04563. Total bilirubin <2 x upper limit of normal [Note: If Baseline laboratory tests are not yet available, then the previous laboratory tests from Week 22 of the parent study (Study P04271) should be used for enrollment. When the Baseline laboratory tests become available, the investigator must apply the above parameters to determine a subject's eligibility.] Subjects must be free of any clinically significant disease (other than plaque-type psoriasis or psoriatic arthritis) that would interfere with the study evaluations. Subjects must be willing to give written informed consent and be able to adhere to dose and visit schedules. Women of childbearing potential and all men must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) and must continue using such measures until 6 months after receiving the last infusion of study medication. Female subjects of childbearing potential must have a negative urine pregnancy test at Baseline. Exclusion Criteria: Subjects who have any significant ongoing adverse events (AEs) or AEs from Study P04271 (NCT00251641) that would prohibit further treatment with infliximab at the time of entry. Subjects originally randomized to methotrexate or subjects who received methotrexate at any time during their participation in Study P04271. Subjects who have non-plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular). Subjects who have current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium). Female subjects who are pregnant, nursing, and both men and women who are planning pregnancy during the study period or during the 6 months after receiving of the last infusion of study medication. Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study. Subjects who are staff personnel directly involved with this study. Subjects who are family members of the investigational study staff.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    Maintenance Infliximab

    Intermittent Infliximab

    Arm Description

    Infliximab 5 mg/kg by body weight every 8 weeks

    Infliximab 5 mg/kg by body weight at Weeks 0, 2, 6 and 14 following a 50% reduction in Psoriasis Area and Severity Index (PASI) from the Study P04271 Baseline

    Outcomes

    Primary Outcome Measures

    Number of Participants Who Achieved Psoriasis Area and Severity Index 75 (PASI75) Response at Week 128
    PASI75 defined as the number of participants who achieved a >=75% improvement in Psoriasis Area and Severity Index (PASI) from the original Baseline in Study P04271 (NCT00251641).

    Secondary Outcome Measures

    Number of Participants Who Achieved PASI75 Response at Week 52
    PASI75 defined as the number of participants who achieved a >=75% improvement in PASI from the original Baseline in Study P04271 (NCT00251641)
    Number of Participants Who Achieved PASI75 Response at Week 100
    PASI75 defined as the number of participants who achieved a >=75% improvement in PASI from the original Baseline in Study P04271 (NCT00251641)
    PASI 6-month Area Under the Curve (AUC); (Time Adjusted Total PASI Score Over the 6 Month Period)
    The PASI 6-month AUC is a time adjusted total PASI score over the 6 month (180 days) period. The AUC is a continuous measurement (not a score on a scale); a lower value is considered better and a higher value is considered worse. The weighted average PASI score over 6 months (using all available PASI scores during a 6 month period [from Day 0 to 180 days]) is obtained by using PASI 6-month AUC /180 days.
    PASI 12-month AUC (Time Adjusted Total PASI Score Over the 12 Month Period)
    The PASI 12-month AUC is a time adjusted total PASI score over the 12 month (360 days) period. The AUC is a continuous measurement (not a score on a scale); and a lower value is considered better. The weighted average PASI score over 12 months (using all available PASI scores during a 12 month period [from Day 0 to 360 days]) is is obtained by using PASI 12-month AUC /360 days.

    Full Information

    First Posted
    July 31, 2006
    Last Updated
    March 13, 2017
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00358670
    Brief Title
    Long-Term Effects of Infliximab in the Treatment of Moderate to Severe Psoriasis [Extension of Study P04271, NCT00251641] (P04563)
    Official Title
    A Long-Term Efficacy and Safety Study of Infliximab in the Treatment of Moderate to Severe Plaque-Type Psoriasis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Terminated
    Why Stopped
    Infusion reactions during re-induction cycles after a period of no treatment. Please see "Purpose" section.
    Study Start Date
    May 2006 (undefined)
    Primary Completion Date
    January 2009 (Actual)
    Study Completion Date
    January 2009 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    This is a long-term, randomized, multi-center, open-label study of infliximab treatment in adults with moderate to severe plaque-type psoriasis. This study is the long-term extension of Study P04271 (NCT00251641); Study P04271 is a Phase 3b, randomized, parallel-group, multicenter, open-label, 26-week study comparing the efficacy and safety of infliximab versus methotrexate in the treatment of adult subjects with moderate to severe plaque-type psoriasis. The objectives of this study are to assess the efficacy and safety of long-term maintenance therapy versus intermittent therapy with 5 mg/kg infliximab in a moderate to severe plaque-type psoriasis population. During an interim safety evaluation of the trial, a higher incidence of serious and severe infusion reactions was observed in the intermittent treatment arm, consisting of a re-induction cycle (maximum of 4 infusions at 0, 2, 6 and 14 weeks) after a period of no treatment compared with the maintenance arm (infusions every 8 weeks without an interruption of treatment). Consequently, the sponsor has terminated the trial. The label will be updated to reflect this new information relating to the use of a re-induction regimen with infliximab.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Psoriasis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    441 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Maintenance Infliximab
    Arm Type
    Active Comparator
    Arm Description
    Infliximab 5 mg/kg by body weight every 8 weeks
    Arm Title
    Intermittent Infliximab
    Arm Type
    Experimental
    Arm Description
    Infliximab 5 mg/kg by body weight at Weeks 0, 2, 6 and 14 following a 50% reduction in Psoriasis Area and Severity Index (PASI) from the Study P04271 Baseline
    Intervention Type
    Biological
    Intervention Name(s)
    infliximab
    Other Intervention Name(s)
    SCH 215596, Remicade
    Intervention Description
    Infliximab maintenance therapy intravenous (IV) infusion every 8 weeks, 5 mg/kg body weight (first infusion at Week 4/Visit 2).
    Intervention Type
    Biological
    Intervention Name(s)
    infliximab
    Other Intervention Name(s)
    SCH 215596, Remicade
    Intervention Description
    Infliximab intermittent therapy: Paricipants will receive no infliximab treatment until the Week 26 improvement in PASI from Baseline (original Study P04271 [NCT00251641] Baseline) is reduced by more than 50%. At that time, participants will receive an infliximab infusion, 5 mg/kg body weight. Participants may receive additional infusions at 0, 2, 6, and 14 weeks after the first infusion of the cycle (ie, a maximum of 4 infusions in each infusion cycle) as needed until they respond, defined as a >=75% improvement in PASI from the original Baseline in Study P04271. Subjects will receive no further treatment until they relapse again (ie, improvement in PASI from Baseline is reduced by more than 50%), at which time participants will receive another infusion cycle of up to 4 infusions, as described above. Throughout the study, intermittent treatment infusion cycles will be repeated whenever participants relapse.
    Primary Outcome Measure Information:
    Title
    Number of Participants Who Achieved Psoriasis Area and Severity Index 75 (PASI75) Response at Week 128
    Description
    PASI75 defined as the number of participants who achieved a >=75% improvement in Psoriasis Area and Severity Index (PASI) from the original Baseline in Study P04271 (NCT00251641).
    Time Frame
    128 weeks
    Secondary Outcome Measure Information:
    Title
    Number of Participants Who Achieved PASI75 Response at Week 52
    Description
    PASI75 defined as the number of participants who achieved a >=75% improvement in PASI from the original Baseline in Study P04271 (NCT00251641)
    Time Frame
    52 weeks
    Title
    Number of Participants Who Achieved PASI75 Response at Week 100
    Description
    PASI75 defined as the number of participants who achieved a >=75% improvement in PASI from the original Baseline in Study P04271 (NCT00251641)
    Time Frame
    100 Weeks
    Title
    PASI 6-month Area Under the Curve (AUC); (Time Adjusted Total PASI Score Over the 6 Month Period)
    Description
    The PASI 6-month AUC is a time adjusted total PASI score over the 6 month (180 days) period. The AUC is a continuous measurement (not a score on a scale); a lower value is considered better and a higher value is considered worse. The weighted average PASI score over 6 months (using all available PASI scores during a 6 month period [from Day 0 to 180 days]) is obtained by using PASI 6-month AUC /180 days.
    Time Frame
    Day 0 to 180 days
    Title
    PASI 12-month AUC (Time Adjusted Total PASI Score Over the 12 Month Period)
    Description
    The PASI 12-month AUC is a time adjusted total PASI score over the 12 month (360 days) period. The AUC is a continuous measurement (not a score on a scale); and a lower value is considered better. The weighted average PASI score over 12 months (using all available PASI scores during a 12 month period [from Day 0 to 360 days]) is is obtained by using PASI 12-month AUC /360 days.
    Time Frame
    Day 0 to 360 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Subjects must have met all inclusion/exclusion criteria in Study P04271 (NCT00251641). Subjects must have been originally randomized to infliximab in Study P04271. Subjects must have completed the full 26 weeks of Study P04271. Subjects must have remained on infliximab for the full 22 weeks of treatment in Study P04271. Subjects must have achieved an improvement in Psoriasis Area and Severity Index (PASI) score >=75% from Baseline of Study P04271 to Week 26 of Study P04271. Subjects must agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet light sources during the study. Subjects are considered eligible according to the following tuberculosis (TB) criteria: Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination; Have had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study medication. Subjects' Baseline (Visit 1) clinical laboratory tests (complete blood count, blood chemistry, and urinalysis) must be within the following parameters: Hemoglobin >=10 g/dL White blood cells >=3.5 x 10^9/L Neutrophils >=1.5 x 10^9/L Platelets >=100 x 10^9/L Serum creatinine <1.5 mg/dL (or <133 umol/L) Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase levels as outlined in Protocol P04563. Total bilirubin <2 x upper limit of normal [Note: If Baseline laboratory tests are not yet available, then the previous laboratory tests from Week 22 of the parent study (Study P04271) should be used for enrollment. When the Baseline laboratory tests become available, the investigator must apply the above parameters to determine a subject's eligibility.] Subjects must be free of any clinically significant disease (other than plaque-type psoriasis or psoriatic arthritis) that would interfere with the study evaluations. Subjects must be willing to give written informed consent and be able to adhere to dose and visit schedules. Women of childbearing potential and all men must be using adequate birth control measures (eg, abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, or surgical sterilization) and must continue using such measures until 6 months after receiving the last infusion of study medication. Female subjects of childbearing potential must have a negative urine pregnancy test at Baseline. Exclusion Criteria: Subjects who have any significant ongoing adverse events (AEs) or AEs from Study P04271 (NCT00251641) that would prohibit further treatment with infliximab at the time of entry. Subjects originally randomized to methotrexate or subjects who received methotrexate at any time during their participation in Study P04271. Subjects who have non-plaque forms of psoriasis (eg, erythrodermic, guttate, or pustular). Subjects who have current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium). Female subjects who are pregnant, nursing, and both men and women who are planning pregnancy during the study period or during the 6 months after receiving of the last infusion of study medication. Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study. Subjects who are staff personnel directly involved with this study. Subjects who are family members of the investigational study staff.

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php
    Citations:
    PubMed Identifier
    23621698
    Citation
    Reich K, Wozel G, Zheng H, van Hoogstraten HJ, Flint L, Barker J. Efficacy and safety of infliximab as continuous or intermittent therapy in patients with moderate-to-severe plaque psoriasis: results of a randomized, long-term extension trial (RESTORE2). Br J Dermatol. 2013 Jun;168(6):1325-34. doi: 10.1111/bjd.12404.
    Results Reference
    result

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    Long-Term Effects of Infliximab in the Treatment of Moderate to Severe Psoriasis [Extension of Study P04271, NCT00251641] (P04563)

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