Osteoarthritis, Knee
Conditions
Keywords
Osteoarthritis, Knee, Pain, Intra-articular, Injection, Corticosteroid
Brief summary
This is an open-label study assessing the effect of the administration of a single intra-articular (IA) injection of FX006 32 mg on synovial volume in patients with osteoarthritis (OA) of the knee.
Detailed description
This is an open-label study assessing the effect of the administration of a single intra-articular (IA) injection of FX006 32 mg on synovial volume in patients with osteoarthritis (OA) of the knee. The study will be conducted in male and female patients who are ≥ 40 years of age. Eligible patients who provide written consent and meet all entry criteria will undergo initial ultrasound examination and MRI with contrast of the index knee, and then receive a single IA injection of FX006 administered to the index knee at Baseline/Day 1. Patients will return to the clinic at Weeks 6 and 24 for an MRI with contrast of the index knee and other assessments. Patients must also have a blood sample drawn for Estimated Glomerular Filtration Rate (eGFR) testing within 30 days prior to the scheduled MRIs. In addition, a patient questionnaire will be administered and adverse events (AEs) and concomitant medication updates will be collected via telephone at Weeks 12 and 18.
Interventions
DRUGFX006 32 mg
Extended-release 32 mg FX006 IA injection
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Written consent to participate in the study * Male or female ≥ 40 years of age * Body mass index (BMI) ≤ 40 kg/m\^2 * Ambulatory and in good general health * Willing and able to comply with the study procedures and visit schedules and able to follow verbal and written instructions * Willing to abstain from use of protocol-restricted medications during the study * Symptoms associated with OA of the index knee for ≥ 6 months prior to Screening (patient self-report is acceptable) * Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA * Kellgren-Lawrence (K-L) Grade 2 or 3 in the index knee based on X-ray performed during Screening (centrally read)
Exclusion criteria
* Any inflammatory arthritis including reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, gout or secondary OA from gout * History of infection or crystal disease in the index knee joint * Unstable index knee joint (such as a torn anterior cruciate ligament) within 12 months of Screening * Surgery or arthroscopy of the index knee within 12 months of Screening * IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening * IA treatment of the index knee with hyaluronic acid (investigational or marketed) within 6 months of Screening * IV or IM corticosteroids (investigational or marketed) within 3 months of Screening * Oral corticosteroids (investigational or marketed) within 1 month of Screening * Any other IA drug/biologic in the index knee within 6 months of Screening or 5 half-lives (whichever is longer) (e.g., platelet rich plasma (PRP) injection, stem cells, prolotherapy and amniotic fluid injection) * Prior administration of FX006 * eGFR results \<40 mL/minute * Any contraindication to MRI Scanning (e.g., presence of certain ferromagnetic foreign bodies or electronic devices including most cardiac pacemakers, claustrophobia) * Known hypersensitivity to any form of radiographic contrast * Females who are pregnant or nursing or plan to become pregnant during the study; men who plan to conceive during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Standardized Change in Synovial Volume (SV) at 6 Weeks | Baseline to Week 6 | Synovial volume (mm\^3) as measured by MRI and read by a central imaging vendor. Standardization was performed by dividing the model-derived least squares means and corresponding confidence intervals by the adjusted standard deviation (SD). Therefore, the mean standardized change represents the change in synovial volume expressed in standard deviation units. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Absolute Change in Synovial Volume at 6 Weeks | Baseline to Week 6 | Mean absolute change from baseline at 6 weeks in synovial volume (mm\^3) as measured by MRI and read by a central imaging vendor. The least squares mean changes are estimated using a mixed effects model for repeated measures with fixed effects for study time point, study site, baseline score and baseline femur bone volume (mm\^3) and a random effect for patient. |
| Mean Standardized Change in Synovial Volume (SV) at 24 Weeks | Baseline to Week 24 | Synovial volume (mm\^3) as measured by MRI and read by a central imaging vendor. Standardization was performed by dividing the model-derived least squares means and corresponding confidence intervals by the adjusted standard deviation (SD). Therefore, the mean standardized change represents the change in synovial volume expressed in standard deviation units. |
| Mean Absolute Change in Synovial Volume at 24 Weeks | Baseline to Week 24 | Mean absolute change (mm\^3) from baseline at 24 weeks in synovial volume (mm\^3) as measured by MRI and read by a central imaging vendor. The least squares mean changes are estimated using a mixed effects model for repeated measures with fixed effects for study time point, study site, baseline score and baseline femur bone volume (mm\^3) and a random effect for patient. |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Total Population All patients who received any amount of FX006 32mg | 129 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 7 |
| Overall Study | Needle inserted but no drug administered | 1 |
| Overall Study | Personal reasons | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 13 |
Baseline characteristics
| Characteristic | Total Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 44 Participants |
| Age, Categorical Between 18 and 65 years | 85 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 108 Participants |
| Region of Enrollment United States | 129 participants |
| Sex: Female, Male Female | 81 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 129 | 0 / 102 |
| other Total, other adverse events | 31 / 129 | 28 / 102 |
| serious Total, serious adverse events | 1 / 129 | 1 / 102 |
Outcome results
Primary
Mean Standardized Change in Synovial Volume (SV) at 6 Weeks
Synovial volume (mm\^3) as measured by MRI and read by a central imaging vendor. Standardization was performed by dividing the model-derived least squares means and corresponding confidence intervals by the adjusted standard deviation (SD). Therefore, the mean standardized change represents the change in synovial volume expressed in standard deviation units.
Time frame: Baseline to Week 6
Population: Participants with pre-treatment synovial volume measurement as determined by quantitative image analysis, as well as a quality Week 6 MRI who received a single intra-articular (IA) injection of FX006 32 mg
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Total Population | Mean Standardized Change in Synovial Volume (SV) at 6 Weeks | -0.67 Standardized Units |
| Patients With Baseline Synovitis | Mean Standardized Change in Synovial Volume (SV) at 6 Weeks | -0.9 Standardized Units |
Secondary
Mean Absolute Change in Synovial Volume at 24 Weeks
Mean absolute change (mm\^3) from baseline at 24 weeks in synovial volume (mm\^3) as measured by MRI and read by a central imaging vendor. The least squares mean changes are estimated using a mixed effects model for repeated measures with fixed effects for study time point, study site, baseline score and baseline femur bone volume (mm\^3) and a random effect for patient.
Time frame: Baseline to Week 24
Population: Participants with pre-treatment synovial volume measurement as determined by quantitative image analysis, as well as a quality Week 24 MRI who received a single intra-articular (IA) injection of FX006 32 mg.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Total Population | Mean Absolute Change in Synovial Volume at 24 Weeks | 3239.94 mm^3 | Standard Error 1184.58 |
| Patients With Baseline Synovitis | Mean Absolute Change in Synovial Volume at 24 Weeks | 3476.52 mm^3 | Standard Error 1408.7997 |
Secondary
Mean Absolute Change in Synovial Volume at 6 Weeks
Mean absolute change from baseline at 6 weeks in synovial volume (mm\^3) as measured by MRI and read by a central imaging vendor. The least squares mean changes are estimated using a mixed effects model for repeated measures with fixed effects for study time point, study site, baseline score and baseline femur bone volume (mm\^3) and a random effect for patient.
Time frame: Baseline to Week 6
Population: Participants with pre treatment synovial volume measurement as determined by quantitative image analysis, as well as a quality Week 6 MRI who received a single intra-articular (IA) injection of FX006 32 mg
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Total Population | Mean Absolute Change in Synovial Volume at 6 Weeks | -5469.68 mm^3 | Standard Error 581.9123 |
| Patients With Baseline Synovitis | Mean Absolute Change in Synovial Volume at 6 Weeks | -7549.55 mm^3 | Standard Error 683.6488 |
Secondary
Mean Standardized Change in Synovial Volume (SV) at 24 Weeks
Synovial volume (mm\^3) as measured by MRI and read by a central imaging vendor. Standardization was performed by dividing the model-derived least squares means and corresponding confidence intervals by the adjusted standard deviation (SD). Therefore, the mean standardized change represents the change in synovial volume expressed in standard deviation units.
Time frame: Baseline to Week 24
Population: Participants with pre treatment synovial volume measurement as determined by quantitative image analysis, as well as a quality Week 24 MRI who received a single intra-articular (IA) injection of FX006 32 mg
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Total Population | Mean Standardized Change in Synovial Volume (SV) at 24 Weeks | 0.20 Standardized Units |
| Patients With Baseline Synovitis | Mean Standardized Change in Synovial Volume (SV) at 24 Weeks | 0.20 Standardized Units |