Proof of Concept Study Comparing FX006 to Kenalog®-40 in Patients With Post-Traumatic Osteoarthritis of the Knee

Study Overview
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Brief Summary
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This study was a double-blind, randomized, parallel group, proof of concept study comparing FX006 to Kenalog®-40 (triamcinolone acetonide injectable suspension, USP) in patients with post-traumatic osteoarthritis of the knee.

Detailed Description
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This study was a double-blind, randomized, parallel group, proof of concept study patients with post-traumatic osteoarthritis (PTOA) of the knee. Approximately 124 eligible patients were intended to be randomized to one of the two treatment groups (1:1) and treated with a single intra-articular (IA) injection of: 32 mg of FX006 40 mg of Kenalog®-40 (triamcinolone acetonide injectable suspension, USP) Each prospective patient underwent a screening evaluation to confirm a diagnosis of PTOA of the knee and concurrence with all other eligibility criteria. Patients were be treated on Day 1 (Baseline) and returned to the clinic at Weeks 4, 8 and 12 for evaluation of safety and efficacy.

Official Title
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A Double-Blind, Randomized, Parallel Group, Proof of Concept Study Comparing FX006 to Kenalog®-40 in Patients With Post-Traumatic Osteoarthritis of the Knee

Conditions
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Post-traumatic Osteoarthritis of the Knee

Intervention / Treatment
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* Drug: FX006 32 mg
* Drug: TCA IR 40 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions Male or female ≥20 and ≤50 years of age Diagnosis of post-traumatic OA of the knee Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee within 6 months prior to or at Screening Qualifying mean score on the 24-h average pain score (0-10 numeric rating scale) Body mass index (BMI) ≤ 40 kg/m2 Willingness to abstain from use of restricted medications and therapies during the study Exclusion Criteria: Prior osteotomy of the index knee Any condition that could possibly confound the patient's assessment of index knee pain in the judgement of the Investigator (i.e., ipsilateral hip OA, gout, radicular low back pain and hip pain that is referred to the knee that could cause misclassifcation, pain in any other area of the lower extremeties or back that is equal to or greater than the index knee pain) Fibromyalgia, Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease History of, or clinical signs and symptoms of active infection of the index knee Crystal disease of the index knee within one month of Screening Disease secondary to surgical treatment of Shatzker grade IV, V, or VI tibial plateau fractures (OTA classification C2 or C3); surgical treatment of OTA calssifcation C2 or C3 distal femur fractures; or >2mm of articular incongruity after surgery IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening Intramuscular (IM) or oral corticosteroids (investigational or marketed) within 1 month of Screening Any other IA investigational drug/biologic within 6 months of Screening Prior use of FX006 Prior arthroplasty of any type of the index knee or planned/anticipated surgery of the index knee during the study period Type 1 or Type 2 diabetes requiring insulin Women of child-bearing potential not using effective contraception or who are pregnant or nursing

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FX006 32mg<br>Single 5 mL intra-articular (IA) injection Extended-release formulation | Drug: FX006 32 mg<br>* Experimental<br>* Other names: Zilretta;|
| Active Comparator: TCA IR 40 mg<br>Single 1 mL intra-articular (IA) injection Immediate-release formulation | Drug: TCA IR 40 mg<br>* Comparator<br>* Other names: Triamcinolone Acetonide Crystalline Suspension (TAcs);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Change From Baseline in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores Over Weeks 5 to 10 | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. | 5-10 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores, Change From Baseline to Each Week and Average Change From Baseline Over Weeks 1 to 12 and Weeks 4 to 12 | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. | 12 Weeks | 
| Proportion of Patients Experiencing a >20% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Each Week |  | 12 Weeks | 
| Proportion of Patients Experiencing a >50% or >30% Decrease in Pain From Baseline in Weekly Mean of Average Daily 24-hr Pain Intensity Scores at Each Week |  | 12 Weeks | 
| Proportion of Patients Experiencing Each of >50% or >30% Decrease in Pain From Baseline in Weekly Mean of the Average Daily (24-hr) Pain Intensity Scores at Each Week |  | 12 Weeks | 
| WOMAC A (Pain Subscale) | change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12 | 12 weeks | 
| WOMAC A1 (Pain on Walking Question) | change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12 | 12 weeks | 
| WOMAC B (Stiffness) | change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12 | 12 weeks | 
| WOMAC C (Function) | change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12 | 12 weeks | 
| WOMAC (Total): | change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12 | 12 weeks | 
| Knee Injury and Osteoarthritis Score (KOOS) | change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12 | 12 weeks | 
| Patient Global Impression of Change (PGIC) at Weeks 4, 8 and 12 |  | 12 weeks | 
| Clinical Global Impression of Change (CGIC) at Weeks 4, 8 and 12 |  | 12 weeks | 
| Percent of Responders (Defined as Patients With High Improvement in Pain or Function) According to OMERACT-OARSI Criteria at Weeks 4, 8 and 12 |  | 12 weeks | 
| Time to Onset of Pain Relief | Time to onset of pain relief in days is defined as the time from first dose to the first daily pain assessment showing >30% improvement from the weekly mean of the average daily (24-hr) pain intensity scores at Baseline | Baseline to >30% improvement | 
| Average Weekly and Total Consumption of Rescue Medication |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritis, Post-traumatic, Knee, Pain, Corticosteroid, Intra-articular, Injection