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Treatment Of Knee Osteoarthritis With Intra-Articular Infliximab

This study has been completed.
Sponsor:
Collaborator:
Centocor a division of Johnson and Johnson
Information provided by:
University of Kansas
ClinicalTrials.gov Identifier:
NCT01144143
First received: June 10, 2010
Last updated: January 11, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Osteoarthritis, Knee
Drug: Infliximab
Drug: Placebo
Drug: Standard of Care: Methylprednisolone acetate
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Single Center, Randomized, Double-Blind, Placebo-Controlled Treatment Of Knee Osteoarthritis With Intra-Articular Infliximab

Resource links provided by NLM:


Further study details as provided by University of Kansas:

Primary Outcome Measures:
  • Measure reduction in cellular infiltrates in synovial tissue four weeks after IA infliximab therapy. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measure reduction in suprapatellar pouch and joint effusions, synovial vascularity and synovial membrane thickness. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Measure change in WOMAC and ClinHAQ II scores. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Measure change in clinical findings of knees by blinded physician assessor. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Measure changes in levels of circulating proteins related to cartilage metabolism by ELISA. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
  • Measure changes in levels of circulating T cell subsets and monocytes by flow cytometry. [ Time Frame: screening, baseline, day 28 ] [ Designated as safety issue: No ]

Estimated Enrollment: 16
Study Start Date: July 2007
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Infliximab Drug: Infliximab
the study drug will be injected into the joint through a needle
Placebo Comparator: Salt Water Drug: Placebo
the placebo will be injected into the joint through a needle
Active Comparator: Methylprednisolone acetate Drug: Standard of Care: Methylprednisolone acetate
Methylprednisolone acetate will be injected into the joint through a needle

Detailed Description:

This is an unbalanced randomized, double-blind pilot study of Infliximab (100 mg), placebo (100 mg) and Methylprednisolone acetate (80 mg). A total of 16 subjects will be randomized; 8 subjects will be randomized to receive infliximab, 4 subjects will be randomized to receive placebo and 4 additional subjects will be randomized to receive Methylprednisolone acetate. Subjects will be seen at screening, day 0, day 14, day 28 and day 56. After study drug injection at day 0, patients will return for follow-up visits at approximately 2 weeks, 1 and 2 months in order to obtain clinical endpoint measures for a total of 10 weeks. Outcome measures include blood tests, MRI, ultrasound, synovial lining tissue biopsy questionnaires and adverse events.

  Eligibility

Ages Eligible for Study:   35 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01144143

Locations
United States, Kansas
University Of Kansas Medical Center
Kansas City, Kansas, United States, 66160
Sponsors and Collaborators
University of Kansas
Centocor a division of Johnson and Johnson
Investigators
Principal Investigator: Herbert Lindsley, MD University of Kansas
  More Information

No publications provided

Responsible Party: Herbert Lindsley, MD, University Of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT01144143     History of Changes
Other Study ID Numbers: 10702
Study First Received: June 10, 2010
Last Updated: January 11, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Kansas:
Mild to moderate osteoarthritis of the knee

Additional relevant MeSH terms:
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Infliximab
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents
Central Nervous System Agents
Dermatologic Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents

ClinicalTrials.gov processed this record on November 25, 2014