AMZ001 for the Treatment of Knee Osteoarthritis Symptoms

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 4-week trial of a formulation of AMZ001 once or twice daily versus placebo twice daily, including a single-blind treatment group with a commercial gel four times daily.

Detailed Description
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This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 4-week trial of a formulation of AMZ001 once or twice daily versus placebo twice daily, including a single-blind treatment group with a commercial gel four times daily. Participants will be evaluated for osteoarthritis by X-ray images of the knees and one knee will be selected for treatment as the target knee. The study gel will be applied directly to that knee throughout the 4 weeks of the study.

Official Title
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A Placebo-controlled, Double-blind, Randomized, Trial of AMZ001 for the Treatment of Knee Osteoarthritis Symptoms

Conditions
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Osteoarthritis, Knee

Intervention / Treatment
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* Drug: AMZ001
* Drug: Placebo
* Drug: Comparator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Osteoarthritis of the knee, according the American College of Rheumatology (ACR) clinical and X-ray criteria. Pain score rated on an 11-point numerical rating scale of the target knee of ≥ 20 and ≤ 45 out of 50 in response to the WOMAC pain sub-score (5 questions), at the time of screening, after washout of any pain relief medication. Women of child-bearing potential must use at least an acceptably effective method of contraception from enrollment up to at least 3 months after the study end. Knee pain in the target knee for 14 days of the preceding month (knee pain due to osteoarthritis and not due to another condition such as bursitis, tendinitis, etc.) based on subject report. On stable pain therapy (i.e., at least 3 days per week for the previous month) with an oral or topical NSAID prescribed by physician for 30 days prior to the Screening Visit and/or prescribed over-the-counter. Except for osteoarthritis, in reasonably good health as determined by the Investigator. Exclusion Criteria: Known or suspected hypersensitivity to diclofenac, other non-steroidal anti-inflammatory drugs or related substances including aspirin, any of the components in either of the investigation products, or any physical impediment to gel application on the target knee. Injection 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 oral/injected corticosteroid treatment of more than 14 days during the past 6 months prior to screening. Major surgery or arthroscopy of the target knee within the previous year prior to screening. Planned surgery of the target knee within the next 3 months. Presence of an additional non-osteoarthritic disease affecting either knee, such as rheumatoid arthritis, psoriasis, gout or pseudo-gout, if there is reason to believe that the disease(s) may significantly interfere with the interpretation of the clinical response to the study drug. Medical history of coronary artery bypass graft surgery. Current cancer or treatment for cancer within the past five years, with the exception of non-melanoma skin cancer, unless affecting the target knee area. Secondary osteoarthritis of the target knee, previous procedures or trauma affecting joint of the target knee. Reported incidence of any of the following diseases: known osteoarthritis of the hip(s) if pain in hip(s) exceeds that of the target knee using the WOMAC Hip Pain subscore, presence of significant back pain, or at least one migraine attack within the past 12 months before screening, as reported by the subject. Body Mass Index > 45.0 kg/m2. 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. Known presence of a ulcer or any gastrointestinal bleeding within 6 months prior to screening. Use of moderate or higher doses of opioid medication for the treatment of pain 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.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: placebo-controlled, double-blind, randomized, parallel study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMZ001 + Placebo<br>on the target knee | Drug: AMZ001<br>* diclofenac gel<br>|
| Experimental: AMZ001<br>on the target knee | Drug: AMZ001<br>* diclofenac gel<br>|
| Placebo Comparator: Placebo<br>on the target knee | Drug: Placebo<br>* Placebo<br>|
| Active Comparator: Comparator<br>Diclofenac gel on the target knee | Drug: Comparator<br>* diclofenac gel<br>* Other names: active comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC Pain Sub-score | Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain sub-score (questions 1-5; score 0 [no pain]-50 [extreme pain]) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where higher scores indicate greater pain, stiffness or difficulty in performing daily tasks. | baseline, week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| WOMAC Total Score and WOMAC Function and Stiffness | Change from baseline in Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) total score and WOMAC function (degree of difficulty experienced in performing daily activities - 17 questions score 0-170) and stiffness (the degree and timing of joint stiffness - 2 questions score 0-20). The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks. | baseline, week 4 | 
| WOMAC Pain Weight-bearing Score and Non-weight-bearing Score | Change from baseline in Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) pain weight-bearing score (questions 1,2, & 5; score 0-30) and non-weight-bearing score (questions 3&4; score 0-20) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks. | baseline, week 4 | 
| ICOAP Scores | Change from baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) scores (score 0 [no pain]- 4 [extreme pain]). ICOAP scores were normalized to a 0-100 point scale, where 0 is no pain and higher scores indicate greater pain. | baseline, week 4 | 
| Physical Function | Change in baseline in physical function assessed by the chair-stand test. The test measures the maximum number of chair stand repetitions possible in a 30-second period with out using the arms. Where 0 is no repetition completed and higher numbers corresponds to greater repetitions and physical function. | baseline, week 4 | 
| Proportion of Responders as Per OMERACT-OARSI Criteria | Outcome Measures in Rheumatology- Osteoarthritis Research Society International (OMERACT-OARSI) response involves changes that are deemed to be clinically relevant in three domains: pain, function, and PGA (Patient Global Assessment). For each of these domains, ranges are defined for absolute and percent changes from baseline that correspond to high improvement and moderate improvement. OMERACT-OARSI response is defined as either high improvement in at least 1 of WOMAC pain and function scores OR moderate improvement in at least 2 of WOMAC pain scores, WOMAC function score or Patient Global Assessment (PGA) | week 4 | 
| Total Dose of Rescue Medication | Total dose of rescue medication calculated as the average gram use/day, based on pill counts. | weeks 1 through 4 | 
| Time Between Baseline and First Use of Rescue Medication | Time between baseline and first use of rescue medication. | weeks 1 through 4 | 
| WOMAC Pain Sub-score (Dose Comparison) | Change from baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain sub-score (questions 1-5; score 0 [no pain]-50 [extreme pain]) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks. | baseline, week 4 | 
| ICOAP Scores (Dose Comparison) | Change from baseline in Intermittent and Constant Osteoarthritis Pain (ICOAP) scores (score 0 [no pain]- 4 [extreme pain]). ICOAP scores were normalized to a 0-100 point scale, where 0 is no pain and higher scores indicate greater pain. | baseline, week 4 | 
| WOMAC Pain Weight-bearing Score and Non-weight-bearing Score (Dose Comparison) | Changes from baseline in Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) pain weight-bearing score (questions 1,2, & 5; score 0-30) and non-weight-bearing score (questions 3&4; score 0-20) on target knee. The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks. | baseline, week 4 | 
| Physical Function (Dose Comparison) | Change in baseline assessed by the chair-stand test. The test measures the maximum number of chair stand repetitions possible in a 30-second period with out using the arms. Where 0 is no repetition completed and higher numbers corresponds to greater repetitions and physical function. | baseline, week 4 | 
| WOMAC Total Score and WOMAC Function and Stiffness (Dose Comparison) | Change from baseline in Western Ontario McMasters Universities Osteoarthritis Index (WOMAC) total score and WOMAC function (degree of difficulty experienced in performing daily activities - 17 questions score 0-170) and stiffness (the degree and timing of joint stiffness - 2 questions score 0-20). The WOMAC scores were normalized to a 0-100 point scale for data analysis, where 0 is no pain and higher scores indicate greater pain, stiffness or difficulty in performing daily tasks. | baseline, week 4 | 
| Impact of Osteoarthritis on Daily Living (PGA Score) | Change from baseline in Impact of OA daily living assessed using Patient Global Assessment (PGA) score. PGA is scored on a 11-point scale from 0 (none) to 10 (extreme), where higher scores represents a higher level of disease activity or worse health. | baseline, week 4 | 
| Work Productivity | Change from baseline in work productivity and activity assessed by the Work Productivity and Active Impairment (WPAI scores 0-100% in four different categories: absenteeism, presenteeism, work productivity loss, and activity impairment). Outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. | baseline, week 4 | 
| Change in Quality of Life: EQ5D VAS Score | The EuroQol-5 Domain (EQ-5D) is a standardized generic measure of health-related quality of life. The visual analog scale (VAS) is scored on a 0-100 scale, where 0 is the worst health you can imagine and 100, the best health you can imagine. | baseline, week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMZ001