Osteoarthritis, Knee
Conditions
Keywords
Inflammatory Type
Brief summary
This is a Canadian randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the clinical efficacy and safety of adalimumab versus placebo when used to treat subjects with a diagnosis of osteoarthritis of the knee, and with clinical features of inflammation, whose pain persists despite receiving maximum tolerated doses of conventional therapy.
Detailed description
This is a Canadian randomized, double-blind, placebo-controlled, multicenter study designed to evaluate the clinical efficacy and safety of adalimumab versus placebo when used to treat subjects with a diagnosis of osteoarthritis of the knee, and with clinical features of inflammation, whose pain persists despite receiving maximum tolerated doses of conventional therapy. A total of 100 subjects will be entered into the study. Subjects will be randomized (1:1) at baseline to receive either adalimumab 40 mg every other week or placebo for 16 weeks. The study drug will be self-administered via subcutaneous injection. Efficacy will be assessed at week 16 while the safety of the study drug will be monitored throughout the study. At week 16 all subjects will begin to receive open label adalimumab 40 mg every other week.
Interventions
DRUGAdalimumab 40 mg
Adalimumab will be self-administered via subcutaneous (SC) injection
DRUGPlacebo
Placebo will be self-administered via subcutaneous (SC) injection
Sponsors
AbbVie
CARE ARTHRITIS LTD.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Endpoint: the percentage of subjects achieving an Osteoarthritis Research Society International/Outcome Measures in Rheumatology Clinical trials (OARSI/OMERACT) response at Week 16 | 16 weeks | The primary efficacy outcome measure will be the percentage of subjects achieving an OARSI/OMERACT response at Week 16. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary endpoint KOOS composite pain 20/50 response rates | 16 weeks | 2\. KOOS composite pain 20/50 response rates, i.e., the percentages of subjects showing ≥ 20% and ≥ 50% improvements from baseline in KOOS composite pain scores in the index knee at 16 weeks. |
| Secondary Endpoint KOOS activities of daily living score | 16 Weeks | 3\. KOOS activities of daily living score at 16 weeks. |
| Secondary Endpoint KOOS symptoms score | 16 weeks | 4\. KOOS symptoms score at 16 weeks. |
| Secondary Endpoint KOOS sport and recreation function score | 16 weeks | 5\. KOOS sport and recreation function score at 16 weeks. |
| Secondary Endpoint KOOS knee-related quality of life score | 16 weeks | 6\. KOOS knee-related quality of life score at 16 weeks. |
| Secondary endpoint Knee Injury and Osteoarthritis Outcome (KOOS) composite pain score at 16 weeks. | 16 weeks | 1\. KOOS composite pain score at 16 weeks. |
| Secondary Endpoint Investigator global assessment of disease status score | 16 Weeks | 8\. Investigator global assessment of disease status score at 16 weeks. |
| Secondary Endpoint Physical assessment of Target Joint | 16 weeks | 9\. Physical assessment of Target Joint at 16 weeks. |
| Secondary Endpoint Expanded Target Joint Assessment score | 16 weeks | 10\. Expanded Target Joint Assessment score at 16 weeks. |
| Secondary Endpoint Average weekly consumption of analgesic medications | 16 weeks | 11\. Average weekly consumption of analgesic medications over 16 weeks. |
| Secondary Endpoint Patient global assessment of disease status score | 16 weeks | 7\. Patient global assessment of disease status score at 16 weeks. |
Countries
Canada
Outcome results
None listed