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Evaluation of Low Dose Infliximab in Ankylosing Spondylitis (Study P04352) (CANDLE)

Primary Purpose

Spondylitis, Ankylosing

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

About this trial

This is an interventional treatment trial for Spondylitis, Ankylosing

Eligibility Criteria

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

Inclusion Criteria: Are men or women >=18 years of age at Screening. Female subjects of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active during the study) must be using an acceptable method of birth control (eg, hormonal contraceptive, medically prescribed IUD, condom in combination with spermicide) or be surgically sterilized (eg, hysterectomy or tubal ligation), and must continue such precautions for 6 months after receiving the last study agent infusion, and have a negative serum pregnancy test prior to enrollment. Additionally, male subjects who are sexually active, with women of childbearing potential, should ensure that they or their partners are using adequate contraception Have had a diagnosis of AS according to the modified 1984 New York criteria, prior to Screening. Have active disease, as evidenced by a BASDAI score of >=4 at Baseline and at Screening Screening tests must meet the following criteria: Hemoglobin: >=9.0 g/dL (5.6 mmol/L) for men and >=8.5 g/dL (5.3 mmol/L) for women Serum transaminase levels must be within 3 times the ULN Serum creatinine <=1.4 mg/dL (107umol/L). Are capable of reading and understanding subject assessment forms and providing written informed consent. Have had a documented negative reaction to a PPD skin test (PPD induration < 5 mm) performed within 1 month prior to the first study infusion. If PPD negative, chest x-ray still required. Subjects must understand English or French. Exclusion Criteria: Have had a serious infection (eg, sepsis, hepatitis, abscesses, pneumonia, or pyelonephritis), have been hospitalized for an infection, or have been treated with intravenous (IV) antibiotics for an infection within 8 weeks prior to randomization. Less serious infections (eg, acute upper respiratory tract infection, or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator. Have ever had a chronic or recurrent infectious disease including, but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), open, draining, or infected skin wound, or ulcer. Have ever had opportunistic infections (eg, herpes zoster (shingles), cytomegalovirus, pneumocystis carinii, aspergillosis, histoplasmosis) Have had documented an atypical mycobacteria infection. Have had active TB or recent close contact with an individual with active TB or ever had evidence of latent TB. Have a chest radiograph (PA and lateral) that displays granulomas or apical fibronodular disease suggestive of previous TB as determined by the investigator. Have documented Hepatitis B (surface antigen positive). Have documented HIV. Have a known malignancy or history of malignancy within 5-year period prior to Screening (with the exception of squamous or basal cell carcinoma of the skin that has been completely excised without evidence of recurrence). Have a history of lymphoproliferative disease including lymphoma, have multiple sclerosis, or other central demyelinating disorder, or have congestive heart failure. Have a serious concomitant illness, other than the ones mentioned above, that might interfere with participation in the trial. Have a known allergy to murine proteins or other chimeric proteins. Have ever received any previous treatment with infliximab, etanercept or other anti-TNF agents prior to first study infusion. Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter. Have a contraindication to any study protocol component. Subjects who have a contraindication to the MRI component of the study can be enrolled, however, they will be exempt from all MRI examinations. Subjects with unstable doses of NSAIDS, DMARDs, analgesics or corticosteroids at Screening who will continue to receive these medications during the study. Subjects who are receiving >10 mg of prednisone (or equivalent) daily. Have a documented history of fibromyalgia confirmed by an appropriate physician specialist (ie, rheumatologist). Have had a documented history of total ankylosis.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    1

    2

    Arm Description

    Outcomes

    Primary Outcome Measures

    The proportion of AS assessment responders ASAS20 (ie, a minimum 20% improvement from Baseline according to the ASAS response criteria) at Week 12.

    Secondary Outcome Measures

    Change from Baseline in the magnetic resonance imaging activity score at Week 12.
    Change from Baseline in BASFI at Week 12 and Week 50.
    Change from Baseline in BASDAI at Week 12 and Week 50.
    Change from Baseline in BASGI at Week 12 and Week 50.
    Change from Baseline in spinal mobility (BASMI) at Week 12 and Week 50.
    Change from Baseline in spinal mobility (EDASMI) at Week 12 and Week 50.
    Proportion of subjects achieving an ASAS40 at Week 12 and Week 50.
    Proportion of subjects achieving an ASAS50 at Week 12 and Week 50.
    Proportion of subjects achieving an ASAS70 at Week 12 and Week 50.
    Change from Baseline in the physical component of the SF-36 at Week 12 and Week 50.
    Assess the treatment survival.
    Quantify the number of subjects requiring dose titration.
    Assess predictors of response.
    Assess predictors of toxicity.

    Full Information

    First Posted
    September 16, 2005
    Last Updated
    March 22, 2017
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00202865
    Brief Title
    Evaluation of Low Dose Infliximab in Ankylosing Spondylitis (Study P04352)
    Acronym
    CANDLE
    Official Title
    CANaDian Evaluation of Low DosE Infliximab in Ankylosing Spondylitis
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2017
    Overall Recruitment Status
    Completed
    Study Start Date
    May 1, 2005 (Actual)
    Primary Completion Date
    May 1, 2007 (Actual)
    Study Completion Date
    May 1, 2007 (Actual)

    3. Sponsor/Collaborators

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

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a randomized, double-blind, multi-center, placebo-controlled study with two parallel treatment groups (placebo and infliximab) in subjects with ankylosing spondylitis (AS) to evaluate the efficacy of infliximab 3 mg/kg.

    6. Conditions and Keywords

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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    76 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    1
    Arm Type
    Experimental
    Arm Title
    2
    Arm Type
    Placebo Comparator
    Intervention Type
    Biological
    Intervention Name(s)
    infliximab
    Other Intervention Name(s)
    Remicade, SCH 215596
    Intervention Description
    Infliximab 3 mg/kg infusions at Weeks 0, 2, and 6 and every 8 weeks thereafter. Subjects who lose response according to a pre-specified criteria at weeks 22 or 38 visit will increase the dose of infliximab to 5 mg/kg (rounded up to the nearest vial).
    Intervention Type
    Biological
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo infusions at Weeks 0, 2, and 6. Subjects will be evaluated at Week 12 after which they will receive infliximab 3 mg/kg at Weeks 16, 18, and 22 then every 8 weeks. Subjects who lose response according to a pre-specified criteria at weeks 22 or 38 visit will increase the dose of infliximab to 5 mg/kg (rounded up to the nearest vial).
    Primary Outcome Measure Information:
    Title
    The proportion of AS assessment responders ASAS20 (ie, a minimum 20% improvement from Baseline according to the ASAS response criteria) at Week 12.
    Time Frame
    Week 12
    Secondary Outcome Measure Information:
    Title
    Change from Baseline in the magnetic resonance imaging activity score at Week 12.
    Time Frame
    Week 12
    Title
    Change from Baseline in BASFI at Week 12 and Week 50.
    Time Frame
    Week 12 and Week 50
    Title
    Change from Baseline in BASDAI at Week 12 and Week 50.
    Time Frame
    Week 12 and Week 50
    Title
    Change from Baseline in BASGI at Week 12 and Week 50.
    Time Frame
    Week 12 and Week 50
    Title
    Change from Baseline in spinal mobility (BASMI) at Week 12 and Week 50.
    Time Frame
    Week 12 and Week 50
    Title
    Change from Baseline in spinal mobility (EDASMI) at Week 12 and Week 50.
    Time Frame
    Week 12 and Week 50
    Title
    Proportion of subjects achieving an ASAS40 at Week 12 and Week 50.
    Time Frame
    Week 12 and Week 50
    Title
    Proportion of subjects achieving an ASAS50 at Week 12 and Week 50.
    Time Frame
    Week 12 and Week 50
    Title
    Proportion of subjects achieving an ASAS70 at Week 12 and Week 50.
    Time Frame
    Week 12 and Week 50
    Title
    Change from Baseline in the physical component of the SF-36 at Week 12 and Week 50.
    Time Frame
    Week 12 and Week 50
    Title
    Assess the treatment survival.
    Time Frame
    From baseline to week 50
    Title
    Quantify the number of subjects requiring dose titration.
    Time Frame
    Week 22 and 38
    Title
    Assess predictors of response.
    Time Frame
    Week 12 and 50
    Title
    Assess predictors of toxicity.
    Time Frame
    50 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Are men or women >=18 years of age at Screening. Female subjects of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active during the study) must be using an acceptable method of birth control (eg, hormonal contraceptive, medically prescribed IUD, condom in combination with spermicide) or be surgically sterilized (eg, hysterectomy or tubal ligation), and must continue such precautions for 6 months after receiving the last study agent infusion, and have a negative serum pregnancy test prior to enrollment. Additionally, male subjects who are sexually active, with women of childbearing potential, should ensure that they or their partners are using adequate contraception Have had a diagnosis of AS according to the modified 1984 New York criteria, prior to Screening. Have active disease, as evidenced by a BASDAI score of >=4 at Baseline and at Screening Screening tests must meet the following criteria: Hemoglobin: >=9.0 g/dL (5.6 mmol/L) for men and >=8.5 g/dL (5.3 mmol/L) for women Serum transaminase levels must be within 3 times the ULN Serum creatinine <=1.4 mg/dL (107umol/L). Are capable of reading and understanding subject assessment forms and providing written informed consent. Have had a documented negative reaction to a PPD skin test (PPD induration < 5 mm) performed within 1 month prior to the first study infusion. If PPD negative, chest x-ray still required. Subjects must understand English or French. Exclusion Criteria: Have had a serious infection (eg, sepsis, hepatitis, abscesses, pneumonia, or pyelonephritis), have been hospitalized for an infection, or have been treated with intravenous (IV) antibiotics for an infection within 8 weeks prior to randomization. Less serious infections (eg, acute upper respiratory tract infection, or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator. Have ever had a chronic or recurrent infectious disease including, but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), open, draining, or infected skin wound, or ulcer. Have ever had opportunistic infections (eg, herpes zoster (shingles), cytomegalovirus, pneumocystis carinii, aspergillosis, histoplasmosis) Have had documented an atypical mycobacteria infection. Have had active TB or recent close contact with an individual with active TB or ever had evidence of latent TB. Have a chest radiograph (PA and lateral) that displays granulomas or apical fibronodular disease suggestive of previous TB as determined by the investigator. Have documented Hepatitis B (surface antigen positive). Have documented HIV. Have a known malignancy or history of malignancy within 5-year period prior to Screening (with the exception of squamous or basal cell carcinoma of the skin that has been completely excised without evidence of recurrence). Have a history of lymphoproliferative disease including lymphoma, have multiple sclerosis, or other central demyelinating disorder, or have congestive heart failure. Have a serious concomitant illness, other than the ones mentioned above, that might interfere with participation in the trial. Have a known allergy to murine proteins or other chimeric proteins. Have ever received any previous treatment with infliximab, etanercept or other anti-TNF agents prior to first study infusion. Are pregnant, nursing, or planning pregnancy (both men and women) during the trial or within the 6-month period thereafter. Have a contraindication to any study protocol component. Subjects who have a contraindication to the MRI component of the study can be enrolled, however, they will be exempt from all MRI examinations. Subjects with unstable doses of NSAIDS, DMARDs, analgesics or corticosteroids at Screening who will continue to receive these medications during the study. Subjects who are receiving >10 mg of prednisone (or equivalent) daily. Have a documented history of fibromyalgia confirmed by an appropriate physician specialist (ie, rheumatologist). Have had a documented history of total ankylosis.

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    20231198
    Citation
    Inman RD, Maksymowych WP; CANDLE Study Group. A double-blind, placebo-controlled trial of low dose infliximab in ankylosing spondylitis. J Rheumatol. 2010 Jun;37(6):1203-10. doi: 10.3899/jrheum.091042. Epub 2010 Mar 15.
    Results Reference
    result
    Available IPD and Supporting Information:
    Available IPD/Information Type
    CSR Synopsis
    Available IPD/Information URL
    http://www.merck.com/clinical-trials/policies-perspectives.html

    Learn more about this trial

    Evaluation of Low Dose Infliximab in Ankylosing Spondylitis (Study P04352)

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