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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00202865
• Date of registration: 16/09/2005
• Prospective Registration: No
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public title: Evaluation of Low Dose Infliximab in Ankylosing Spondylitis (Study P04352) CANDLE
• Scientific title: CANaDian Evaluation of Low DosE Infliximab in Ankylosing Spondylitis
• Date of first enrolment: May 1, 2005
• Target sample size: 76
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00202865
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Canada

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Spondylitis, Ankylosing

Intervention(s)

Biological: infliximab

Biological: Placebo

Primary Outcome(s)

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(s)

Change from Baseline in BASFI 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]

Quantify the number of subjects requiring dose titration. [Time Frame: Week 22 and 38]

Change from Baseline in the magnetic resonance imaging activity score at Week 12. [Time Frame: Week 12]

Proportion of subjects achieving an ASAS70 at Week 12 and Week 50. [Time Frame: Week 12 and Week 50]

Assess the treatment survival. [Time Frame: From baseline to week 50]

Proportion of subjects achieving an ASAS40 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]

Assess predictors of response. [Time Frame: Week 12 and 50]

Assess predictors of toxicity. [Time Frame: 50 weeks]

Change from Baseline in the physical component of the SF-36 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]

Secondary ID(s)

P04352

2472

Source(s) of Monetary Support

Please refer to primary and secondary sponsors