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

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ClinicalTrials.gov Identifier: NCT00202865
Recruitment Status : Completed
First Posted : September 20, 2005
Last Update Posted : March 24, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE September 16, 2005
First Posted Date  ICMJE September 20, 2005
Last Update Posted Date March 24, 2017
Actual Study Start Date  ICMJE May 1, 2005
Actual Primary Completion Date May 1, 2007   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 22, 2008)
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 ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00202865 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 22, 2008)
  • Change from Baseline in the magnetic resonance imaging activity score at Week 12. [ Time Frame: Week 12 ]
  • Change from Baseline in BASFI at Week 12 and Week 50. [ Time Frame: Week 12 and Week 50 ]
  • Change from Baseline in BASDAI at Week 12 and Week 50. [ Time Frame: Week 12 and Week 50 ]
  • Change from Baseline in BASGI at Week 12 and Week 50. [ Time Frame: Week 12 and Week 50 ]
  • Change from Baseline in spinal mobility (BASMI) at Week 12 and Week 50. [ Time Frame: Week 12 and Week 50 ]
  • Change from Baseline in spinal mobility (EDASMI) at Week 12 and Week 50. [ Time Frame: Week 12 and Week 50 ]
  • Proportion of subjects achieving an ASAS40 at Week 12 and Week 50. [ Time Frame: Week 12 and Week 50 ]
  • Proportion of subjects achieving an ASAS50 at Week 12 and Week 50. [ Time Frame: Week 12 and Week 50 ]
  • Proportion of subjects achieving an ASAS70 at Week 12 and Week 50. [ Time Frame: Week 12 and Week 50 ]
  • Change from Baseline in the physical component of the SF-36 at Week 12 and Week 50. [ Time Frame: Week 12 and Week 50 ]
  • Assess the treatment survival. [ Time Frame: From baseline to week 50 ]
  • Quantify the number of subjects requiring dose titration. [ Time Frame: Week 22 and 38 ]
  • Assess predictors of response. [ Time Frame: Week 12 and 50 ]
  • Assess predictors of toxicity. [ Time Frame: 50 weeks ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Low Dose Infliximab in Ankylosing Spondylitis (Study P04352)
Official Title  ICMJE CANaDian Evaluation of Low DosE Infliximab in Ankylosing Spondylitis
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Spondylitis, Ankylosing
Intervention  ICMJE
  • Biological: infliximab
    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).
    Other Names:
    • Remicade
    • SCH 215596
  • Biological: Placebo
    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).
Study Arms  ICMJE
  • Experimental: 1
    Intervention: Biological: infliximab
  • Placebo Comparator: 2
    Intervention: Biological: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 22, 2008)
76
Original Enrollment  ICMJE
 (submitted: September 16, 2005)
80
Actual Study Completion Date  ICMJE May 1, 2007
Actual Primary Completion Date May 1, 2007   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT00202865
Other Study ID Numbers  ICMJE P04352
2472
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Merck Sharp & Dohme Corp.
Verification Date March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP