A Randomized, Double-Blind, Multi-Center, Placebo-Controlled, Trial to Evaluate the Efficacy and Safety of Once Daily Diclofenac Gel AMZ001 3.06% in the Treatment of Pain and Symptoms of Knee Osteoarthritis

Who can take part

• Participant is able to read and understand the language and content of the study material, understand the requirements for study visits, and is willing to provide information at the scheduled evaluations and appropriate written informed consent has been obtained
• Knee pain in the target knee for at least 14 days of the preceding month (periarticular knee pain due to OA and not due to non-OA conditions such as bursitis, tendonitis, etc.) based on participant report
• Except for OA, the participant is in reasonably good health as determined by the Investigator
• Femorotibial OA of the knee, according to the American College of Rheumatology (ACR) clinical and radiographic criteria (Altman et al. 1986)
• Radiological OA grade 2, or 3 of the target knee, using the Kellgren-Lawrence method (Kellgren and Lawrence 1957) as graded by central, independent reading of X-ray obtained during screening, or on a recent (within 6 months) X-ray image which fulfills the specifications for central reading
• Age between 40 years and 85 years at the time of screening, both included of either sex
• Pain score rated on an 11-point numerical rating scale of the target knee of ≥ 20 out of 50 in response to the WOMAC pain sub-score (5 questions), at the time of screening and baseline
• The WOMAC pain sub-score on the contralateral knee must not exceed the one on the target knee, regardless of the eligibility of the contralateral knee, at the time of screening and baseline
• At screening Visit 1a, participants report that their typical OA knee pain in one or both knees when not using medication is ≥ 4 out of 10
• Daily OA knee pain diary average numerical rating scale (NRS) score of ≥ 4 and ≤ 9 in the target knee, for the 7 days immediately preceding baseline (Day 1). The average calculation is based on the recorded scores during this entire period with a requirement of at least 4 days of data recorded
• Women of child-bearing potential must use a highly effective method of contraception (hormonal contraceptives, intrauterine device, vasectomy, bilateral tubal occlusion, sexual abstinence) from enrolment up to at least 3 months after the study end. Postmenopausal status is defined as being amenorrheic for at least 1 year prior to screening. Sexually active men with a female partner of childbearing potential must agree to use condom from enrolment up to at least 3 months after the study end

Who cannot take part

• Known or suspected hypersensitivity to or previous hypersensitivity reactions to diclofenac or of the excipients in either of the investigational products
• Patients in whom asthma, angioedema, urticaria, or acute rhinitis are precipitated by acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs)
• Use of any topical medication on the planned application site within 15 days of the time of randomization
• Any use of opioid medication within 6 weeks before the screening visit
• Use of duloxetine, pregabalin, or gabapentin within 4 weeks before the screening visit
• History of alcohol or drug abuse within the past year prior to randomization
• Intra-articular delivery of corticosteroids or hyaluronic acid in the target knee within 6 months of screening or into any other joint within 30 days of screening
• High dose (equivalent to > 10 mg of prednisone/day) systemic corticosteroid treatment of more than 14 days during the past 6 months prior to screening
• Major surgery /arthroscopy of the target knee within the previous year prior to screening or aspiration of effusion of the target knee within 12 weeks prior to enrollment
• Perioperative period in the setting of coronary artery bypass graft surgery
• Planned surgery of the target knee within the next 12 months
• Use of a currently unapproved investigational drug, device or biologic within 3 months prior to screening
• Presence of concomitant non-osteoarthritic disease affecting either knee, such as rheumatoid arthritis, psoriasis, gout or clinically relevant pseudogout, if there is reason to believe that the disease(s) may significantly interfere with the interpretation of the clinical response to the study drug
• Secondary OA of the target knee, previous procedures or trauma affecting joint homeostasis including total meniscectomy or septic arthritis, or any other serious condition leading to secondary OA of the target knee
• Generalized skin irritation, previous skin reactions upon use of topical NSAIDs, current skin irritation or redness at the planned site of gel application, or significant skin disease including psoriasis, as judged by the investigator
• Current malignancy or treatment for malignancy within the past five years, with the exception of non-melanoma skin cancer, unless affecting the target knee area, or carcinoma in situ events
• Reported incidence of any of the following diseases: known osteoarthritis of the hip(s) if pain in either or both hip(s) exceeds that of the target knee using the WOMAC hip pain sub-score, or presence of significant radicular back pain
• Any other abnormal laboratory results or significant medical conditions that the Investigator believes should preclude the participant’s participation in the trial
• Estimated glomerular filtration rate (eGFR) < 30 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI 2021) formula
• Pregnant and breastfeeding women are excluded for participation
• Any physical impediment to gel application on the target knee
• Presence of a defined cut-off of pain variability during the screening period of 1.5 out of 10: · Pain Numeric Rating Scale (NRS) scores must be recorded for the target knee on at least 4 out of the 7 days immediately preceding baseline (Day 1) · Observed standard deviation of the Daily osteoarthritis (OA) knee pain diary average NRS intensity score for 7 days immediately preceding baseline (Day 1) must not exceed 1.5