Osteoarthritis of the KneePhase 4NCT01144143
Treatment Of Knee Osteoarthritis With Intra-Articular Infliximab
A Phase 4 study testing Infliximab in people with Osteoarthritis of the Knee, run by Herbert Lindsley, MD at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 85 years
- Conditions the study is for
- Osteoarthritis of the Knee
- What is being tested?
- Infliximab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Jan 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults ≥ age 35 but ≤ age 85.
- Painful knees for 3-60 months.
- VAS joint pain score greater than 30 mm (scale 0-100)
- Knee radiograph showing minimal to moderate change (early OA).
- No NSAID therapy for at least one week.
- Have the capacity to understand and sign an informed consent form.
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- Gender: Male or female
- 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.
- 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.
- The screening laboratory test results must meet the following criteria
- WBC (white blood cell count): >3.5/uL
- Hemoglobin: > 10 gm/dl
- Platelets: > 100,000/ul
- Serum Creatinine: < 1.8
- SGPT (ALT - alanine aminotransferase) <3 times ULN
- UA (urinalysis) with microscopic exam: WNL
- Negative tests for HbsAg or hepatitis C Ab
- PT/PTT: WNL
- Are considered eligible according to the following TB screening criteria:
- 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.
- Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
- 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.
- 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.
- 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.
Who cannot join
- Moderate to Severe OA, as determined by severe joint space narrowing (Kellgren grade IV) (7) in medial and lateral compartments
- Insulin-dependent diabetes mellitus.
- Systemic inflammatory illness, e.g. rheumatoid arthritis.
- Intra-articular injections within 3 months.
- Prior treatment with infliximab or other anti-TNF drug.
- Acute injury to knees (< 2 weeks)
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- 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).
- Have had any previous treatment with monoclonal antibodies or antibody fragments.
- 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
- Documentation of a positive test for hepatitis B surface antigen or hepatitis C.
- 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.
- Have a known history of serious infections (e.g., hepatitis, pneumonia, or pyelonephritis) in the previous 3 months.
- 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
- Currently receiving Coumadin, Ticlid, Plavix, or heparin/heparin analog within 7 days prior to synovial biopsy.
- Currently receiving aspirin within 7 days prior to synovial biopsy.
- Have a chest radiograph at screening that shows evidence of malignancy or infection.
- 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.
- 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.
- Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
- Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
- Use of any investigational drug within 30 days prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
- Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening).
- Have a concomitant diagnosis or history of congestive heart failure Grade III-IV.
- Have had a nontuberculous mycobacterial infection or opportunistic infection (e.g., cytomegalovirus, Pneumocystis carinii, and aspergillosis) within 6 months prior to screening.
Trial locations and contacts
1 site in 1 country.
United States1 site
University Of Kansas Medical Center
Kansas City, Kansas, 66160
About this study
Official title: Single Center, Randomized, Double-Blind, Placebo-Controlled Treatment Of Knee Osteoarthritis With Intra-Articular Infliximab
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.
Read the 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.
- Conditions
- Osteoarthritis of the Knee
- Being tested
- Infliximab, Placebo, Standard of Care: Methylprednisolone acetate
- Keywords
- Mild to moderate osteoarthritis of the knee
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
the study drug will be injected into the joint through a needle
PlaceboDrug
the placebo will be injected into the joint through a needle
Standard of Care: Methylprednisolone acetateDrug
Methylprednisolone acetate will be injected into the joint through a needle
| Study group | Role | What they receive |
|---|---|---|
| Infliximab | Experimental | Not described Receives: Drug: Infliximab |
| Salt Water | Placebo comparator | Not described Receives: Drug: Placebo |
| Methylprednisolone acetate | Active comparator | Not described Receives: Drug: Standard of Care: Methylprednisolone acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cellular Infiltrates From Day 0 to Day 28
Cellular infiltration scored 0 to 3
Measured: Day 0 to Day 28
Secondary outcomes (5)
Change in Joint Effusions From Day 0 to Day 56 Target Knee
Outcome calculated based on Physician observation of joint swelling from 0-3. A score of 0 = no effusion,1 = positive "bulge," 2 = moderate effusion, 3 = tense effusion. The outcome represents the change in means between the two time points.
Measured: Change from Day 0 to Day 56
Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Score Target Knee
The WOMAC questionnaire is used to evaluate the condition of patients with osteoarthritis. Patients answer questions based on how they are feeling. The questionnaire has a total of 24 questions which deal with pain, stiffness and physical function. Participants are asked to respond to how difficult it is for them to do/complete an activity. There is a total possible score of 96. A score of 0 equals no difficulty completing any of the 24 activities. A score of 96 would indicate extreme difficulty with all activities.
Measured: Change from Day 0 to Day 56
Change in Levels of Serum IL-6
Measured: Change from Day 0 to Day 56
Change in Serum CRP Day 0 to Day 56
Serum measure of systemic inflammation
Measured: Day 0 to Day 56
Change in Serum SAA Levels Day 0 to Day 56
Serum Amyloid A
Measured: Day 0 to Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2010 (estimated)
- Study startJul 2007
- Primary completionDec 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Osteoarthritis of the KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herbert Lindsley, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Centocor, Inc.
- Responsible party
- Sponsor-investigator, Herbert Lindsley, MD, University of Kansas Medical Center
- Investigators
- Herbert Lindsley, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01144143
- Sponsor's protocol ID
- 10702
- Status last verified
- Jan 2018
- First submitted
- 10 Jun 2010
- Last updated
- 8 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Center, Randomized, Double-Blind, Placebo-Controlled Treatment Of Knee Osteoarthritis With Intra-Articular Infliximab
- ClinicalTrials.gov ID
- NCT01144143
- Acronym / sponsor ID
- 10702
- Conditions
- Osteoarthritis of the Knee
- Keywords
- Mild to moderate osteoarthritis of the knee
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Herbert Lindsley, MDUniversity, hospital or other
- Collaborators
- Centocor, Inc.
- Study start
- Jul 2007
- Primary completion
- Dec 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 15 Jun 2010 (estimated)
- Results
- Posted 8 Feb 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Infliximab | Experimental | Drug: Infliximab |
| Salt Water | Placebo comparator | Drug: Placebo |
| Methylprednisolone acetate | Active comparator | Drug: Standard of Care: Methylprednisolone acetate |
Who may qualify
- Ages
- 35 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Adults ≥ age 35 but ≤ age 85.
- Painful knees for 3-60 months.
- VAS joint pain score greater than 30 mm (scale 0-100)
- Knee radiograph showing minimal to moderate change (early OA).
- No NSAID therapy for at least one week.
Key exclusion criteria (24 listed)
- Moderate to Severe OA, as determined by severe joint space narrowing (Kellgren grade IV) (7) in medial and lateral compartments
- Insulin-dependent diabetes mellitus.
- Systemic inflammatory illness, e.g. rheumatoid arthritis.
- Intra-articular injections within 3 months.
- Prior treatment with infliximab or other anti-TNF drug.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Infliximabthe study drug will be injected into the joint through a needle | Drug | Infliximab |
| Placebothe placebo will be injected into the joint through a needle | Drug | Salt Water |
| Standard of Care: Methylprednisolone acetateMethylprednisolone acetate will be injected into the joint through a needle | Drug | Methylprednisolone acetate |
Primary outcome
Change in Cellular Infiltrates From Day 0 to Day 28
Time frame: Day 0 to Day 28
Cellular infiltration scored 0 to 3
5 secondary outcomes
Change in Joint Effusions From Day 0 to Day 56 Target Knee
Time frame: Change from Day 0 to Day 56
Change in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Score Target Knee
Time frame: Change from Day 0 to Day 56
Change in Levels of Serum IL-6
Time frame: Change from Day 0 to Day 56
Change in Serum CRP Day 0 to Day 56
Time frame: Day 0 to Day 56
Change in Serum SAA Levels Day 0 to Day 56
Time frame: Day 0 to Day 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Herbert Lindsley, MD principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Infliximab in people with Osteoarthritis of the Knee, run by Herbert Lindsley, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cellular Infiltrates From Day 0 to Day 28 (time frame: Day 0 to Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2018.