A Placebo-Controlled, Double-Blinded, Randomized Trial of Remicade in Korean Patients With Rheumatoid Arthritis Despite Methotrexate (Study P04280)(COMPLETED)

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00202852
• Date of registration: 13/09/2005
• Prospective Registration: No
• Primary sponsor: Merck Sharp & Dohme Corp.
• Public title: A Placebo-Controlled, Double-Blinded, Randomized Trial of Remicade in Korean Patients With Rheumatoid Arthritis Despite Methotrexate (Study P04280)(COMPLETED)
• Scientific title: A Placebo-Controlled, Double-Blinded, Randomized Clinical Trial of Anti-TNF Chimeric Monoclonal Antibody (cA2) in Korean Patients With Active Rheumatoid Arthritis Despite Methotrexate
• Date of first enrolment: June 1, 2005
• Target sample size: 143
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00202852
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Korea, Republic of

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of RA according to the revised 1987 criteria of the American Rheumatism
Association (Arnett et al, 1988). The disease should have been diagnosed at least 6
months prior to screening.

- Active disease at the time of screening and pre-infusion as defined by:

- >=6 swollen joints

- >=6 tender joints and 2 of the following:

- morning stiffness >=45 min

- ESR >=28 mm/h

- CRP >=20 mg/L

- Men and women, >=18 to <=75 years of age

- Men and women of childbearing potential must be using adequate birth control measures
(abstinence, oral contraceptives, IUD, barrier method with spermicide or, surgical
sterilization) and should continue such precautions for 6 months after receiving the
last infusion.

- Patients must have been using oral or parenteral MTX for at least 3 months with no
break(s) in treatment of more than 2 weeks total during this period. Patients must
have been on a stable dose of >=12.5 mg/wk (maximum 20mg/wk) for at least 4 weeks
prior to screening.

- Patients must be on a stable dose of folic acid prophylaxis for at least 4 weeks prior
to screening.

- Patients using oral corticosteroids, must have been on a stable dose of <=10 mg/day
for at least 4 weeks prior to screening. If currently not using corticosteroids the
patient must have not received corticosteroids for at least 4 weeks prior to
screening.

- If using NSAIDs, patients should have been on a stable dose for at least 4 weeks prior
to screening. If currently not using NSAIDs the patient must have been off for at
least 4 weeks prior to screening.

- The screening laboratory tests must meet the following criteria:

- Hemoglobin >=5.3 mmol/L (>=8.5 g/dL), providing a low hemoglobin level is not due
to nutritional deficiencies or due to diseases other than chronic RA

- WBC >=3.5 x 10^9/L

- Neutrophils >=1.5 x 10^9/L

- Platelets >=100 x 10^9/L

- Serum transaminase <=2 times the upper limit of normal

- Alkaline phosphatase levels <=2 times the upper limit of normal

- Serum creatinine <=150 µmol/L (<=1.7 mg/dL)

- Patient must be able to adhere to the study visit schedule and other protocol
requirements.

- Patient must be capable of giving informed consent and the consent must have been
obtained prior to any study procedures including wash-out period.

Exclusion Criteria:

- Pregnant women, nursing mothers or a planned pregnancy within 1.5 years of enrollment.

- Patients who are incapacitated, largely or wholly bedridden or confined to a
wheelchair, and who have little or no ability for self-care.

- Patients who have any current systemic inflammatory condition with signs and symptoms
that might confound the evaluations of benefit from the Infliximab therapy, eg Lyme
disease, or a rheumatic disease other than RA.

- Use of DMARDs other than MTX within 4 weeks prior to screening. (If a patient had
prior exposure to leflunomide within the past 6 months, cholestyramine 8 g should be
given 3 times daily for 11 days to rapidly lower the plasma level of leflunomide.)

- Use of intra-articular, i.m. or i.v. corticosteroids (including i.m. ACTH) within 4
weeks prior to screening.

- Have been previously treated with infliximab or genetic recombinant therapy with RA
(e.g. etanercept, adalimumab).

- Treatment with any other therapeutic agent targeted at reducing TNF (eg,
pentoxifylline or thalidomide) within the previous 3 months.

- Treatment with any investigational drug within the previous 3 months.

- Prior use of cyclophosphamide, nitrogen mustard, chlorambucil, or other alkylating
agents.

- Have a history of any clinically significant adverse reaction to murine or chimeric
proteins, including but not limited to allergic reactions.

- History of infected joint prosthesis within previous 5 years.

- Serious infections, such as hepatitis, pneumonia, pyelonephritis in the previous 3
months.

- Chronic infectious disease such as chronic renal infection, chronic chest infection
with bronchiectasis or sinusitis.

- Have active TB. Also excluded are patients who have evidence of latent TB (positive
PPD skin test or a history of latent TB) without adequate therapy for TB initiated
prior to first infusion of study drug. Also excluded are patients with evidence of an
old or latent TB infection without documented adequate therapy, if they will not be
treated with antitubercular therapy during the trial. Patients with a current close
contact with an individual with active TB will also be excluded. Additionally,
patients who have completed treatment for active TB within the previous 2 years are
now explicitly excluded from the trial. Patients with a household member who has a
history of active pulmonary TB should have had a thorough evaluation for TB prior to
study enrollment as recommended by a local infectious disease specialist or published
local guidelines of TB control agencies. Also excluded are patients with opportunistic
infections, including but not limited to evidence of active cytomegalovirus, active
Pneumocystis carinii, aspergillosis, or atypical mycobacterial infection, etc, within
the previous 6 months.

- Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic,
hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral
disease.

- History of lymphoproliferative disease including lymphoma or signs suggestive of
possible lymphoproliferative disease, such as lymphadenopathy of unusual size or
location (such as nodes in the posterior triangle of the neck, infraclavicular,
epitrochlear, or periaortic areas), or splenomegaly.

- Any current known malignancy or history of malignancy within the previous 5 years,
except for squamous or basal cell carcinoma of the skin that have been treated with no
evidence of recurrence.

- Patients with moderate or severe heart failure (NYHA class III/IV)

- Patients with pre-existing or recent onset of central nervous system demyelinating
disorders

- Known recent substance abuse (drug or alcohol).

- Patients in whom multiple venipunctures are not feasible due to poor tolerability or
lack of easy access.

- Have a known infection with HIV or known active hepatitis B/C


Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Arthritis, Rheumatoid

Intervention(s)

Biological: Infliximab

Drug: MTX

Other: Placebo

Primary Outcome(s)

Achievement of a clinical response (according to the ACR criteria) at the 30-week follow-up visit. [Time Frame: 30-week follow-up visit.]

Secondary Outcome(s)

Assessment of adverse events at each of the evaluation visits. [Time Frame: At each evaluation visit.]

Safety evaluations will include measurements of vital signs during and immediately after the infusions of study agents. [Time Frame: During and immediately after the infusions of study agents.]

Routine, laboratory tests (hematology, blood chemistry, and urinalysis) will be performed at Screening, at 2 and 6 weeks, and thereafter every 8 weeks through Week 30 for patients. [Time Frame: At Screening, Week 2, Week 6, and then every 8 weeks thereafter through Week 30.]

Secondary ID(s)

P04280

Source(s) of Monetary Support

Please refer to primary and secondary sponsors