Osteoarthritis of the Knee
Conditions
Keywords
Osteoarthritis, Knee, Pain, Steroid, Intra-articular, Injection
Brief summary
This is an Open-label Study to Assess the Safety of Repeat Dose of FX006 Administered to Patients with Osteoarthritis (OA) of the Knee
Detailed description
This study is an open-label, repeat administration design of 32 mg FX006. The study will be conducted in male and female patients ≥ 40 years of age with symptomatic OA of the knee. Eligible patients will be offered participation to receive an initial intra-articular (IA) injection of FX006 administered to the index knee at Day 1. Patients who receive an initial injection of FX006 will return at Weeks 4 and 8 before being evaluated at 12, 16, 20 and 24 weeks for repeat administration. At the first evaluation where the patient has been determined to meet repeat administration eligibility criteria, the patient will be eligible to receive a second IA injection of FX006. Patients who are eligible to receive a second injection will be evaluated for a total of 52 weeks post initial injection at: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52, regardless of the time at which they receive their second injection. In addition, X-rays will be completed at Screening and Week 52 or End of Study (EOS) for assessment of safety. Patients that do not benefit from the initial treatment as determined by evaluation at Week 12 will complete the study at the Week 12 follow-up visit. Patients who are not eligible for a second injection of FX006 after evaluation at Weeks 12, 16, 20, and 24 will complete the study at the Week 24 follow-up visit.
Interventions
DRUGFX006 32 mg
Single intra-articular 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 * Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions * Male or female ≥ 40 years of age * Symptoms associated with OA of the index knee for ≥ 6 months prior to Screening * Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA * Kellgren-Lawrence (KL) Grade 2, 3 or 4 in the index knee based on X-ray performed during Screening * Qualifying score for WOMAC A at Screening and Day 1/Baseline * Index knee pain for \>15 days over the last month (as reported by the patient) * Body mass index (BMI) ≤ 40 kg/m2 * Ambulatory and in good general health * Willingness to abstain from use of protocol-restricted medications during the study
Exclusion criteria
* Reactive arthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or arthritis associated with inflammatory bowel disease * History of infection in the index knee joint * Clinical signs and symptoms of active knee infection or crystal disease of the index knee within 1 month of Screening * Presence of surgical hardware or other foreign body in the index knee * Unstable index knee joint (such as a torn anterior cruciate ligament) within 12 months of Screening * IA corticosteroid (investigational or marketed) in index knee within 3 months of Screening * IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening * IV or intramuscular (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 use 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 * Women of child-bearing potential not using effective contraception or who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Number of Treatment Emergent Adverse Events (TEAEs) in Patients With Symptomatic Osteoarthritis (OA) of the Knee Who Received Two Doses of 32 mg FX006 | Up to 52 Weeks | Analyses of adverse events (AE) were performed for events considered treatment-emergent (TE) in patients who received two doses of 32 mg FX006. TE was defined as any AE with onset after administration of the 1st dose of study drug or any event present at baseline but worsened in intensity through the study. Severity was graded by the PI using the Common Terminology Criteria for AEs Version 4.0. Grading went from Grade 1 (Mild) to Grade 5 (Death Related to AE). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | 12 Weeks Post Each FX006 Administration | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. WOMAC A is the independent sub-scale for pain that is comprised of 5 questions. WOMAC A was administered at each visit from screening through Week 52/EOS. |
| WOMAC B Stiffness Subscale | 12 Weeks Post Each FX006 Administration | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. WOMAC B is the independent sub-scale for stiffness that is comprised of 2 questions. WOMAC B was administered at each visit from screening through Week 52/EOS. |
| WOMAC C Function Subscale | 12 Weeks Post Each FX006 Administration | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. WOMAC C is the independent sub-scale for function that is comprised of 17 questions. WOMAC C was administered at each visit from screening through Week 52/EOS. |
| Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | Up to 12 Weeks Post Each FX006 Administration | KOOS is a participant (patient)-reported outcome measurement instrument, developed to assess the patient's opinion about their knee and associated problems. The KOOS evaluates both short-term and long-term consequences of knee injury and also consequences of primary osteoarthritis (OA). It holds 42 items in five separately scored sub-scales: KOOS Pain, KOOS Symptoms, Function in daily living, Function in Sport and Recreation, and knee-related Quality of Life (KOOS QOL). Only KOOS QOL sub-scale (Q1-Q4) was used in this study. A Likert scale is used and all items have five possible answer options scored from 0 (No Problem) to 4 (Extreme Problems). Each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems. Higher scores indicate a better quality of life. KOOS was administered at study visits from BL/Day 1 through week 52. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FX006 32 mg Single intra-articular injection
FX006 32 mg: Single intra-articular injection | 208 |
| Total | 208 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Disease Progression (see caveats) | 25 |
| Overall Study | Lack of Efficacy | 7 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Non OA related knee surgery | 1 |
| Overall Study | Withdrawal by Subject | 14 |
| Overall Study | Withdrawn by Investigator/Sponsor | 3 |
Baseline characteristics
| Characteristic | FX006 32 mg |
|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 8.81 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 11 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 170 Participants |
| Region of Enrollment United States | 208 participants |
| Sex: Female, Male Female | 92 Participants |
| Sex: Female, Male Male | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 208 |
| other Total, other adverse events | 93 / 208 |
| serious Total, serious adverse events | 4 / 208 |
Outcome results
Primary
Total Number of Treatment Emergent Adverse Events (TEAEs) in Patients With Symptomatic Osteoarthritis (OA) of the Knee Who Received Two Doses of 32 mg FX006
Analyses of adverse events (AE) were performed for events considered treatment-emergent (TE) in patients who received two doses of 32 mg FX006. TE was defined as any AE with onset after administration of the 1st dose of study drug or any event present at baseline but worsened in intensity through the study. Severity was graded by the PI using the Common Terminology Criteria for AEs Version 4.0. Grading went from Grade 1 (Mild) to Grade 5 (Death Related to AE).
Time frame: Up to 52 Weeks
Population: Received 2 doses of FX006
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FX006 32 mg | Total Number of Treatment Emergent Adverse Events (TEAEs) in Patients With Symptomatic Osteoarthritis (OA) of the Knee Who Received Two Doses of 32 mg FX006 | 336 TEAEs |
Other Pre-specified
Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale
KOOS is a participant (patient)-reported outcome measurement instrument, developed to assess the patient's opinion about their knee and associated problems. The KOOS evaluates both short-term and long-term consequences of knee injury and also consequences of primary osteoarthritis (OA). It holds 42 items in five separately scored sub-scales: KOOS Pain, KOOS Symptoms, Function in daily living, Function in Sport and Recreation, and knee-related Quality of Life (KOOS QOL). Only KOOS QOL sub-scale (Q1-Q4) was used in this study. A Likert scale is used and all items have five possible answer options scored from 0 (No Problem) to 4 (Extreme Problems). Each of the five scores is calculated as the sum of the items included. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems. Higher scores indicate a better quality of life. KOOS was administered at study visits from BL/Day 1 through week 52.
Time frame: Up to 12 Weeks Post Each FX006 Administration
Population: Participants who received a repeat administration of FX006
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 32 mg | Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | Baseline - First Administration | 28.92 score on a scale | Standard Deviation 15.872 |
| FX006 32 mg | Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | 4 Weeks Post First Administration | 58.06 score on a scale | Standard Deviation 22.049 |
| FX006 32 mg | Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | 8 Weeks Post First Administration | 55.34 score on a scale | Standard Deviation 21.791 |
| FX006 32 mg | Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | 12 Weeks Post First Administration | 46.08 score on a scale | Standard Deviation 20.86 |
| FX006 32 mg | Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | Baseline - Second Administration | 33.47 score on a scale | Standard Deviation 17.27 |
| FX006 32 mg | Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | 4 Weeks Post Second Administration | 54.85 score on a scale | Standard Deviation 20.927 |
| FX006 32 mg | Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | 8 Weeks Post Second Administration | 50.92 score on a scale | Standard Deviation 20.781 |
| FX006 32 mg | Knee Injury and Osteoarthritis Outcome Score (KOOS) QOL Subscale | 12 Weeks Post Second Administration | 46.52 score on a scale | Standard Deviation 23.274 |
Other Pre-specified
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. WOMAC A is the independent sub-scale for pain that is comprised of 5 questions. WOMAC A was administered at each visit from screening through Week 52/EOS.
Time frame: 12 Weeks Post Each FX006 Administration
Population: Participants who received a repeat administration of FX006 at weeks 12, 16, 20 or 24.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 32 mg | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | 4 Weeks Post Second Administration | 0.83 score on a scale | Standard Deviation 0.667 |
| FX006 32 mg | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | Baseline - First Administration | 2.15 score on a scale | Standard Deviation 0.58 |
| FX006 32 mg | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | 4 Weeks Post First Administration | 0.66 score on a scale | Standard Deviation 0.581 |
| FX006 32 mg | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | 8 Weeks Post First Administration | 0.83 score on a scale | Standard Deviation 0.663 |
| FX006 32 mg | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | 12 Weeks Post First Administration | 1.29 score on a scale | Standard Deviation 0.765 |
| FX006 32 mg | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | Baseline - Second Administration | 2.00 score on a scale | Standard Deviation 0.639 |
| FX006 32 mg | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | 8 Weeks Post Second Administration | 0.93 score on a scale | Standard Deviation 0.691 |
| FX006 32 mg | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A Pain Subscale | 12 Weeks Post Second Administration | 1.28 score on a scale | Standard Deviation 0.862 |
Other Pre-specified
WOMAC B Stiffness Subscale
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. WOMAC B is the independent sub-scale for stiffness that is comprised of 2 questions. WOMAC B was administered at each visit from screening through Week 52/EOS.
Time frame: 12 Weeks Post Each FX006 Administration
Population: Participants who received a repeat administration of FX006 at weeks 12, 16, 20 or 24.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 32 mg | WOMAC B Stiffness Subscale | Baseline - First Administration | 2.48 score on a scale | Standard Deviation 0.715 |
| FX006 32 mg | WOMAC B Stiffness Subscale | 4 Weeks Post First Administration | 0.74 score on a scale | Standard Deviation 0.662 |
| FX006 32 mg | WOMAC B Stiffness Subscale | 8 Weeks Post First Administration | 0.90 score on a scale | Standard Deviation 0.749 |
| FX006 32 mg | WOMAC B Stiffness Subscale | 12 Weeks Post First Administration | 1.41 score on a scale | Standard Deviation 0.936 |
| FX006 32 mg | WOMAC B Stiffness Subscale | Baseline - Second Administration | 2.16 score on a scale | Standard Deviation 0.824 |
| FX006 32 mg | WOMAC B Stiffness Subscale | 4 Weeks Post Second Administration | 0.88 score on a scale | Standard Deviation 0.764 |
| FX006 32 mg | WOMAC B Stiffness Subscale | 8 Weeks Post Second Administration | 0.99 score on a scale | Standard Deviation 0.837 |
| FX006 32 mg | WOMAC B Stiffness Subscale | 12 Weeks Post Second Administration | 1.40 score on a scale | Standard Deviation 1.007 |
Other Pre-specified
WOMAC C Function Subscale
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. WOMAC C is the independent sub-scale for function that is comprised of 17 questions. WOMAC C was administered at each visit from screening through Week 52/EOS.
Time frame: 12 Weeks Post Each FX006 Administration
Population: Participants who received a repeat administration of FX006 at weeks 12, 16, 20 or 24.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 32 mg | WOMAC C Function Subscale | 4 Weeks Post First Administration | 0.66 score on a scale | Standard Deviation 0.593 |
| FX006 32 mg | WOMAC C Function Subscale | Baseline - First Administration | 2.18 score on a scale | Standard Deviation 0.613 |
| FX006 32 mg | WOMAC C Function Subscale | 8 Weeks Post First Administration | 0.87 score on a scale | Standard Deviation 0.711 |
| FX006 32 mg | WOMAC C Function Subscale | 12 Weeks Post First Administration | 1.28 score on a scale | Standard Deviation 0.801 |
| FX006 32 mg | WOMAC C Function Subscale | Baseline - Second Administration | 1.96 score on a scale | Standard Deviation 0.692 |
| FX006 32 mg | WOMAC C Function Subscale | 4 Weeks Post Second Administration | 0.85 score on a scale | Standard Deviation 0.685 |
| FX006 32 mg | WOMAC C Function Subscale | 8 Weeks Post Second Administration | 0.96 score on a scale | Standard Deviation 0.699 |
| FX006 32 mg | WOMAC C Function Subscale | 12 Weeks Post Second Administration | 1.31 score on a scale | Standard Deviation 0.845 |