Osteoarthritis of the Knee, Inflammation, and the Effect of Adalimumab (OKINADA): A Randomized Placebo-controlled Trial
Overview
- Phase
- Phase 2
- Intervention
- Adalimumab 40 mg
- Conditions
- Osteoarthritis, Knee
- Sponsor
- CARE ARTHRITIS LTD.
- Enrollment
- 62
- Locations
- 7
- Primary Endpoint
- Primary Endpoint: the percentage of subjects achieving an Osteoarthritis Research Society International/Outcome Measures in Rheumatology Clinical trials (OARSI/OMERACT) response at Week 16
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •≥ 40 years of age
- •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.
- •If female and of childbearing potential, serum pregnancy results must be negative at Screening
- •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).
- •Subject has had knee pain for at least 1 month prior to the Screening Visit.
- •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.
- •Has a pain score of ≥ 4 (0-10 NRS) in the index (more symptomatic) knee at Screening and Baseline.
Exclusion Criteria
- •Has a history of an allergic reaction or significant sensitivity to constituents of adalimumab.
- •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.
- •Subject has a BMI over
- •Planned/anticipated surgery of the index knee during the study period.
- •Already scheduled for any surgery during the time of the study or within 70 days after the end of treatment.
- •Prior arthroscopic or open surgery of the index knee within 12 months of Baseline.
- •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.
- •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.
- •History of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease (e.g. multiple sclerosis).
- •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.
Arms & Interventions
1st 50 subjects to Enter the Study
At Baseline, subjects will be randomized (1:1) to receive study drug (Adalimumab or placebo). The study drug will be provided as a subcutaneous injection (pre-filled syringe) either Adalimumab (ADA) 40 mg/0.8 mL,every other week (EOW) or matching placebo for Adalimumab every other week for 16 weeks. 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 ADA 40 mg EOW and will continue to receive open label ADA up to Week 50. An End of Study visit will be done at Week 52. A Telephone Follow-up will be done at Week 62 to review Adverse Events and Concomitant Medications.
Intervention: Adalimumab 40 mg
1st 50 subjects to Enter the Study
At Baseline, subjects will be randomized (1:1) to receive study drug (Adalimumab or placebo). The study drug will be provided as a subcutaneous injection (pre-filled syringe) either Adalimumab (ADA) 40 mg/0.8 mL,every other week (EOW) or matching placebo for Adalimumab every other week for 16 weeks. 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 ADA 40 mg EOW and will continue to receive open label ADA up to Week 50. An End of Study visit will be done at Week 52. A Telephone Follow-up will be done at Week 62 to review Adverse Events and Concomitant Medications.
Intervention: Placebo
2nd group of 50 subjects
At Baseline, subjects will be randomized (1:1) to receive either adalimumab 40 mg every other week or placebo for 16 weeks. All subjects will begin to receive open label adalimumab 40 mg every other week from week 16-week 30, with An End of Study visit at Week 32. A Telephone Follow-up will be done at Week 42 to review Adverse Events and Concomitant Medications.
Intervention: Adalimumab 40 mg
2nd group of 50 subjects
At Baseline, subjects will be randomized (1:1) to receive either adalimumab 40 mg every other week or placebo for 16 weeks. All subjects will begin to receive open label adalimumab 40 mg every other week from week 16-week 30, with An End of Study visit at Week 32. A Telephone Follow-up will be done at Week 42 to review Adverse Events and Concomitant Medications.
Intervention: Placebo
Outcomes
Primary Outcomes
Primary Endpoint: the percentage of subjects achieving an Osteoarthritis Research Society International/Outcome Measures in Rheumatology Clinical trials (OARSI/OMERACT) response at Week 16
Time Frame: 16 weeks
The primary efficacy outcome measure will be the percentage of subjects achieving an OARSI/OMERACT response at Week 16.
Secondary Outcomes
- Secondary endpoint Knee Injury and Osteoarthritis Outcome (KOOS) composite pain score at 16 weeks.(16 weeks)
- Secondary endpoint KOOS composite pain 20/50 response rates(16 weeks)
- Secondary Endpoint KOOS activities of daily living score(16 Weeks)
- Secondary Endpoint KOOS symptoms score(16 weeks)
- Secondary Endpoint KOOS sport and recreation function score(16 weeks)
- Secondary Endpoint KOOS knee-related quality of life score(16 weeks)
- Secondary Endpoint Patient global assessment of disease status score(16 weeks)
- Secondary Endpoint Investigator global assessment of disease status score(16 Weeks)
- Secondary Endpoint Physical assessment of Target Joint(16 weeks)
- Secondary Endpoint Expanded Target Joint Assessment score(16 weeks)
- Secondary Endpoint Average weekly consumption of analgesic medications(16 weeks)