- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00202865
Evaluation of Low Dose Infliximab in Ankylosing Spondylitis (Study P04352) (CANDLE)
March 22, 2017 updated by: Merck Sharp & Dohme LLC
CANaDian Evaluation of Low DosE Infliximab in Ankylosing Spondylitis
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
76
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
|
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:
|
Placebo Comparator: 2
|
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).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
Week 12
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change from Baseline in the magnetic resonance imaging activity score at Week 12.
Time Frame: Week 12
|
Week 12
|
Change from Baseline in BASFI at Week 12 and Week 50.
Time Frame: Week 12 and Week 50
|
Week 12 and Week 50
|
Change from Baseline in BASDAI at Week 12 and Week 50.
Time Frame: Week 12 and Week 50
|
Week 12 and Week 50
|
Change from Baseline in BASGI at Week 12 and Week 50.
Time Frame: Week 12 and Week 50
|
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
|
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
|
Week 12 and Week 50
|
Proportion of subjects achieving an ASAS40 at Week 12 and Week 50.
Time Frame: Week 12 and Week 50
|
Week 12 and Week 50
|
Proportion of subjects achieving an ASAS50 at Week 12 and Week 50.
Time Frame: Week 12 and Week 50
|
Week 12 and Week 50
|
Proportion of subjects achieving an ASAS70 at Week 12 and Week 50.
Time Frame: Week 12 and Week 50
|
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
|
Week 12 and Week 50
|
Assess the treatment survival.
Time Frame: From baseline to week 50
|
From baseline to week 50
|
Quantify the number of subjects requiring dose titration.
Time Frame: Week 22 and 38
|
Week 22 and 38
|
Assess predictors of response.
Time Frame: Week 12 and 50
|
Week 12 and 50
|
Assess predictors of toxicity.
Time Frame: 50 weeks
|
50 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 1, 2005
Primary Completion (Actual)
May 1, 2007
Study Completion (Actual)
May 1, 2007
Study Registration Dates
First Submitted
September 16, 2005
First Submitted That Met QC Criteria
September 16, 2005
First Posted (Estimate)
September 20, 2005
Study Record Updates
Last Update Posted (Actual)
March 24, 2017
Last Update Submitted That Met QC Criteria
March 22, 2017
Last Verified
March 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- P04352
- 2472
Plan for Individual participant data (IPD)
Study Data/Documents
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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