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

Phase 2

Terminated

Conditions: Post-traumatic Osteoarthritis of the Knee

Interventions: Drug: FX006 32 mg
Drug: TCA IR 40 mg

Registration Number: NCT02468583

Lead Sponsor: Pacira Pharmaceuticals, Inc

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 6

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
FX006 32mg	FX006 32 mg	Single 5 mL intra-articular (IA) injection Extended-release formulation
TCA IR 40 mg	TCA IR 40 mg	Single 1 mL intra-articular (IA) injection Immediate-release formulation

Primary Outcome Measures

Name	Time	Method
Average Change From Baseline in the Weekly Mean of the Average Daily (24-hour) Pain Intensity Scores Over Weeks 5 to 10	5-10 Weeks	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."

Secondary Outcome Measures

Name	Time	Method
Clinical Global Impression of Change (CGIC) at Weeks 4, 8 and 12	12 weeks
WOMAC A1 (Pain on Walking Question)	12 weeks	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
WOMAC (Total):	12 weeks	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
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	12 Weeks	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."
WOMAC B (Stiffness)	12 weeks	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
Knee Injury and Osteoarthritis Score (KOOS)	12 weeks	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
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)	12 weeks	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
Patient Global Impression of Change (PGIC) at Weeks 4, 8 and 12	12 weeks
Time to Onset of Pain Relief	Baseline to >30% improvement	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
WOMAC C (Function)	12 weeks	change from Baseline to Weeks 4, 8 and 12 average change from Baseline over Weeks 4 to 8 and Weeks 4 to 12
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
Average Weekly and Total Consumption of Rescue Medication	12 weeks