Clinical trial: Osteoarthritis of the Knee, Inflammation, and the Effect of Adalimumab (OKINADA) (NCT02471118)

Eligibility criteria:
Inclusion Criteria:

          1. ≥ 40 years of age

          2. If female, subject is either not of childbearing potential, defined as postmenopausal
             for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral
             oophorectomy or hysterectomy), or is of childbearing potential and practicing methods
             of birth control.

          3. If female and of childbearing potential, serum pregnancy results must be negative at
             Screening

          4. Has a diagnosis of Osteoarthritis (OA) of the index knee according to American College
             of Rheumatology (ACR) criteria, including radiological evidence of OA
             (Kellgren-Lawrence grades 2 or 3).

          5. Subject has had knee pain for at least 1 month prior to the Screening Visit.

          6. Subject has had knee pain that has persisted despite conventional treatment, defined
             as any one of the following medications taken for at least 1 month in the past:

               -  acetaminophen (2- 4 grams per day)

               -  therapeutic dose range of an NSAID

               -  acetaminophen/codeine combination (i.e. Tylenol No. 2, 3, 4) taken at least 3
                  times daily.

          7. Has a pain score of ≥ 4 (0-10 NRS) in the index (more symptomatic) knee at Screening
             and Baseline.

          8. If the subject is taking Analgesic/NSAIDs, then the Analgesic/NSAIDs has been stable
             for 14 days prior to the Baseline visit.

          9. Has clinical evidence of a knee effusion in the index (more symptomatic) knee at
             Screening and Baseline.

         10. Able and willing to self-administer SC injections or has available qualified person(s)
             to administer SC injections.

         11. Has voluntarily signed and dated an approved informed consent form prior to any
             study-specific procedures.

        Exclusion Criteria:

          1. Has a history of an allergic reaction or significant sensitivity to constituents of
             adalimumab.

          2. Has other bone and articular diseases (antecedents and/or current signs) such as
             chondrocalcinosis, Paget's disease of the ipsilateral limb to the target knee,
             rheumatoid arthritis, aseptic osteonecrosis, gout, septic arthritis, ochronosis,
             acromegaly, haemochromatosis, Wilson's disease, osteochondromatosis, seronegative
             spondylo-arthropathy, mixed connective tissue disease, collagen vascular disease,
             psoriasis, inflammatory bowel disease.

          3. Subject has a BMI over 40.

          4. Planned/anticipated surgery of the index knee during the study period.

          5. Already scheduled for any surgery during the time of the study or within 70 days after
             the end of treatment.

          6. Prior arthroscopic or open surgery of the index knee within 12 months of Baseline.

          7. Has a history of cancer or lymphoproliferative disease other than: Successfully and
             completely treated cervical dysplasia, with no recurrence within the last five years,
             Basal or Squamous Cell Carcinoma that has been adequately treated or excised.

          8. Has had prior treatment with intravenous (IV) immunoglobulin or any investigational
             agent within 30 days or 5 half-lives of the agent from Baseline, whichever is longer.

          9. History of neurologic symptoms suggestive of central nervous system (CNS)
             demyelinating disease (e.g. multiple sclerosis).

         10. History of uncontrolled diabetes, unstable ischemic heart disease, active congestive
             heart failure, New York Heart Association (NHYA) III, IV, inflammatory bowel disease,
             active peptic ulcer disease, recent stroke (within 12 weeks of Screening), or any
             other condition, which in the opinion of the investigator, would put the patient at
             risk by participating in the study.

         11. Has concurrent local or systemic infection that would preclude the use of adalimumab.

         12. Has had a persistent or severe infection(s) requiring hospitalization or treatment
             with IV antibiotics within 30 days, or oral antibiotics within 14 days, prior to
             Baseline.

         13. History of active tuberculosis or listeriosis, or other infections suggestive of
             significant or profound immunosuppression, such as Pneumocystis carinii, aspergillosis
             or other systemic protozoal or fungal infections.

         14. Has latent TB (positive purified protein derivative (PPD) skin test, two-step PPD when
             applicable, and chest X-ray indicative of TB) or has other risk factors for the
             activation of latent TB, e.g. previous exposure to TB, and has not initiated TB
             prophylaxis prior to the first adalimumab treatment.

         15. Will be excluded if the Chest x-ray is found to have changes indicative of old healed
             tuberculous lesion (e.g. calcified nodule, fibrotic scar, apical or basilar pleural
             thickening etc.).

         16. Has a positive serology for Hepatitis B or Hepatitis C that indicates active
             infection.

         17. Has a history of positive HIV status.

         18. Currently taking or likely to begin anti-retroviral therapy at any time during the
             course of the study.

         19. Female subject is pregnant or breast-feeding.

         20. Has a history of clinically significant drug or alcohol abuse in the last year, prior
             to Screening.

         21. Subject, in the opinion of the principal investigator, is unlikely to comply with the
             study protocol or is unsuitable for any other reason.

        Treatment-Related Exclusion Criteria

          1. Subject has received intra-articular injections of steroid and/or hyaluronate
             compounds into the index knee within 12 weeks prior to Baseline.

          2. Subjects using injectable corticosteroids for any medical condition
             (intra-articular/soft tissue injections are allowed, but not in the target knee).

          3. Subjects using indomethacin or oral steroids.

          4. Subjects taking glucosamine and/or chondroitin at screening must discontinue or remain
             on a stable dose, unmodified if at all possible for the entire duration of the study.

          5. If treatment for osteoarthritis (NSAID) or osteoporosis (bisphosphonates, selective
             estrogen receptor modulators) is necessary, it will have to be continued, unmodified
             if at all possible for the entire duration of the study. If the subject does not wish
             to continue them during the study, they must be stopped 14 days prior to the Baseline
             visit.

          6. Subjects who have used compounds containing non-approved agents for arthritis or
             agents claiming to possess disease/structure-modifying properties in the 14 days prior
             to the Baseline visit (see exception above).

          7. Subjects who require acetaminophen at daily doses > 4000 mg (4 g) on a regular basis.

          8. Subjects who are taking lithium carbonate, phenytoin or anticoagulants (with the
             exception of aspirin up to a maximum daily dose of 325 mg).

          9. Subjects who use calcitonin.

         10. Subjects who use immunosuppressive drugs. Subjects that are using methotrexate or
             hydroxychloroquine must withdraw treatment 1 month prior to baseline, to be eligible
             to enter the study.

         11. Topical analgesics and NSAID's cannot be used on the target knee within the 48 hours
             before each study visit.

         12. No new physical modalities of treatment can be introduced and subject must maintain
             normal activity during the study.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 40 Years old.


Patient description (medical language): A 47-year-old woman comes to the office complaining of pain in the calf and knee when she bends down. The pain limits her activity. Her medical history is significant for osteoarthritis, for which she uses nonsteroidal anti-inflammatory drugs (NSAIDs) for the past two years. She is living with her husband and has 3 children. She doesn't smoke but drinks alcohol occasionally. Her vital signs are normal. On physical examination, there is a small effusion in the right knee. The effusion grew a little larger and she developed a tender swelling in the popliteal fossa and calf. Both the pain and swelling worsened as she bent and straightened her knee.

Patient description (patient's own words): I'm a 47-year-old woman, married with 3 kids. I don't smoke and I drink occasionally. I went to the doctor because of pain in my calf and knee when I was bending down. This has been limiting my daily activities. I have been diagnosed with osteoarthritis for which I have taken anti-inflammatory drugs for the past 2 years. The doctor saw a small fluid buildup in my right knee. This buildup became a bit bigger and I have a swollen calf. The pain is worse when I bend and straighten my knee.

Does the patient match the trial criteria? Entailment