Treatment Of Knee Osteoarthritis With Intra-Articular Infliximab
Condition: Osteoarthritis of the Knee
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Intervention: Infliximab; Placebo; Standard of Care: Methylprednisolone acetate
Intervention description: the study drug will be injected into the joint through a needle; the placebo will be injected into the joint through a needle; Methylprednisolone acetate will be injected into the joint through a needle
Intervention MeSH terms: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Infliximab; Prednisolone hemisuccinate; Prednisolone phosphate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 16.0
Sex: All
Minimum age: 35 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Mild to moderate osteoarthritis of the knee

Summary:

      The purpose of this study is to determine if an anti-inflammatory drug, called infliximab,
      will reduce inflammation in the synovial lining in patients with an early stage of
      osteoarthritis of the knee. It will also help determine if the study medication decreases the
      accumulation of synovial fluid and prevents cartilage breakdown.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adults ≥ age 35 but ≤ age 85.

          2. Painful knees for 3-60 months.

          3. VAS joint pain score greater than 30 mm (scale 0-100)

          4. Knee radiograph showing minimal to moderate change (early OA).

          5. No NSAID therapy for at least one week.

          6. Have the capacity to understand and sign an informed consent form.

          7. Gender: Male or female

          8. Women must be postmenopausal (no menstrual period for a minimum of 1 year) or
             surgically sterilized and have a negative serum pregnancy test on entry in the study.
             Men must agree to use adequate birth control during the study for 6 months after the
             infusion of study agent.

          9. Men and women of childbearing potential must use adequate birth control measures
             (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with
             spermicide, implantable or injectable contraceptives or surgical sterilization) for
             the duration of the study and should continue such precautions for 6 months after
             receiving the last infusion.

         10. The screening laboratory test results must meet the following criteria

               1. WBC (white blood cell count): >3.5/uL

               2. Hemoglobin: > 10 gm/dl

               3. Platelets: > 100,000/ul

               4. Serum Creatinine: < 1.8

               5. SGPT (ALT - alanine aminotransferase) <3 times ULN

               6. UA (urinalysis) with microscopic exam: WNL

               7. Negative tests for HbsAg or hepatitis C Ab

               8. PT/PTT: WNL

         11. Are considered eligible according to the following TB screening criteria:

               1. Have no history of latent or active TB prior to screening. An exception is made
                  for subjects who have a history of latent TB (defined for the purposes of this
                  study as having had a positive result from either the tuberculin skin test or the
                  QuantiFERON-TB Gold test prior to screening) and documentation of having
                  completed an adequate treatment regimen for latent TB within 3 years prior to the
                  first administration of study agent under this protocol. Adequate treatment for
                  latent TB is defined according to local country guidelines for immunocompromised
                  patients. If no local guidelines for immunocompromised patients exist, US
                  guidelines must be followed. It is the responsibility of the investigator to
                  verify the adequacy of previous anti-TB treatment and provide appropriate
                  documentation.

               2. Have no signs or symptoms suggestive of active TB upon medical history and/or
                  physical examination.

               3. Have had no recent close contact with a person with active TB or, if there has
                  been such contact, will be referred to a physician specializing in TB to undergo
                  additional evaluation and, if warranted, receive appropriate treatment for latent
                  TB prior to or simultaneously with the first administration of study agent.

               4. Within 1 month prior to the first administration of study agent, either have
                  negative diagnostic TB test results (defined as both a negative tuberculin skin
                  test and a negative QuantiFERON-TB Gold test, as outlined in Attachment 3 and
                  Attachment 4, respectively), or have a newly identified positive diagnostic TB
                  test result (defined as either a positive tuberculin skin test or a positive
                  QuantiFERON-TB Gold test) during screening in which active TB has been ruled out
                  and for which appropriate treatment for latent TB has been initiated either prior
                  to or simultaneously with the first administration of study agent. The tuberculin
                  skin test and QuantiFERON-TB Gold test are not required at screening for subjects
                  with a history of latent TB and documentation of having completed adequate
                  treatment as described in Inclusion Criterion 12a. Furthermore, these subjects
                  are not required to initiate additional treatment for latent TB.

               5. Have a chest radiograph (both posterior-anterior and lateral views), taken within
                  3 months prior to the first administration of study agent and read by a qualified
                  radiologist, with no evidence of current active TB or old inactive TB.

        Exclusion Criteria:

          1. Moderate to Severe OA, as determined by severe joint space narrowing (Kellgren grade
             IV) (7) in medial and lateral compartments

          2. Insulin-dependent diabetes mellitus.

          3. Systemic inflammatory illness, e.g. rheumatoid arthritis.

          4. Intra-articular injections within 3 months.

          5. Prior treatment with infliximab or other anti-TNF drug.

          6. Acute injury to knees (< 2 weeks)

          7. Women who are pregnant, nursing, or planning pregnancy within 6 months after the last
             infusion (this includes father's who plan on fathering a child within 6 months after
             their last infusion).

          8. Have had any previous treatment with monoclonal antibodies or antibody fragments.

          9. History of receiving human/murine recombinant products or a known allergy to murine
             products. A known allergy to murine product is definitely an exclusion criterion

         10. Documentation of a positive test for hepatitis B surface antigen or hepatitis C.

         11. Have a history of alcohol or substance abuse within the preceding 6 months that, in
             the opinion of the investigator, may increase the risks associated with study
             participation or study agent administration, or may interfere with interpretation of
             results.

         12. Have a known history of serious infections (e.g., hepatitis, pneumonia, or
             pyelonephritis) in the previous 3 months.

         13. Have or have had an opportunistic infection (e.g., herpes zoster [shingles],
             cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria
             other than TB) within 6 months prior to screening

         14. Currently receiving Coumadin, Ticlid, Plavix, or heparin/heparin analog within 7 days
             prior to synovial biopsy.

         15. Currently receiving aspirin within 7 days prior to synovial biopsy.

         16. Have a chest radiograph at screening that shows evidence of malignancy or infection.

         17. Have a history of lymphoproliferative disease, including lymphoma or signs suggestive
             of possible lymphoproliferative disease such as lymphadenopathy of unusual size or
             location (e.g., nodes in the posterior triangle of the neck, infraclavicular,
             epitrochlear, or periaortic area), or splenomegaly.

         18. Currently have any known malignancy or have a history of malignancy within the
             previous 5 years, with the exception of basal cell or squamous cell carcinoma of the
             skin that has been fully excised with no evidence of recurrence as well as carcinoma
             in situ of the cervix.

         19. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic,
             hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral
             disease.

         20. Are unable or unwilling to undergo multiple venipunctures because of poor tolerability
             or lack of easy access.

         21. Use of any investigational drug within 30 days prior to screening or within 5
             half-lives of the investigational agent, whichever is longer.

         22. Presence of a transplanted solid organ (with the exception of a corneal transplant > 3
             months prior to screening).

         23. Have a concomitant diagnosis or history of congestive heart failure Grade III-IV.

         24. Have had a nontuberculous mycobacterial infection or opportunistic infection (e.g.,
             cytomegalovirus, Pneumocystis carinii, and aspergillosis) within 6 months prior to
             screening.