Osteoarthritis, Knee
Conditions
Keywords
Osteoarthritis, Knee Pain
Brief summary
This is a randomized, double-blind, placebo-controlled, 2-injection, 52-week study to evaluate the efficacy and safety of intra-articular injections of CNTX-4975-05 in subjects with chronic, moderate-to-severe osteoarthritis knee pain.
Interventions
DRUGPlacebo
Receiving Placebo Injection
DRUGCNTX-4975-05
Receiving CNTX-4975-05 Injection
Sponsors
Centrexion Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or female subjects between 40 and 95 years of age (inclusive) at the time of the Screening Visit with the ability to comply with answering the electronic diary using the study- provided tablet computers. * Confirmation of osteoarthritis (OA) of the knee. * Confirmation of the OA of the index knee. * Moderate to severe pain in the index knee associated with OA must be stable for a minimum of 6 months prior to Screening, as assessed by the investigator. * Body Mass Index (BMI) ≤45 kg/m\^2 * Must have failed 2 or more prior therapies.
Exclusion criteria
* Joint replacement surgery of the index knee at any time, or open surgery of the index knee in the past 24 months. * Prior arthroscopic surgery of the index knee within 6 months of Screening. * Any painful conditions of the index knee due to joint disease other than the OA. * Periarticular pain from any cause. * Other chronic pain anywhere in the body that requires the use of analgesic medications. * Instability of the index knee. * Misalignment (\>10 degrees varus or valgus) of the index knee on standing. * Documented history of neuropathic arthropathy or finding of bony fragmentation in the index knee with imaging. * Physical/ occupational/ chiropractic therapy for the lower extremities or acupuncture for the lower extremities within 30 days of Screening, or need for such therapy during the study. * Plans to have surgery, other invasive procedures, or IA injections while participating in the study. * Has used topical capsaicin on the index knee within 90 days of Screening. * Current use of opioids for any condition other than for OA of the index knee. * Corticosteroid injection into the index knee within 90 days of Screening. * Received IA viscosupplementation (eg, Synvisc®, Hyalgan®) within 90 days of Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in WOMAC A (Pain) Dimension | Baseline, Week 12 | The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome. The pain dimension includes 5 items about the amount of pain experienced doing various activities (walking, stair climbing, nocturnal, at rest, weight bearing). The score ranges from 0 to 50. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Average Weekly Pain With Walking (NPRS 0-10) in the Index Knee | Baseline, Week 12 | Average daily OA pain in the index knee while walking was evaluated using a 0 to 10 Numerical Pain Rating Scale (NPRS) (0 = no pain and 10 = worst possible pain). 0 was the best score and 10 was the worst score. Subjects used an ePRO at bedtime (9:00 PM ± 3 hours) to record on a daily basis their average daily OA knee pain score with walking during the previous 24 hours. |
| Mean Change From Study Baseline in WOMAC B (Stiffness) Dimension | Baseline, Week 12 | The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome. The stiffness dimension has 2 items: joint stiffness upon wakening and joint stiffness later in the day. The score ranges from 0 to 20. |
| Mean Change From Study Baseline in WOMAC C (Function) Dimension | Baseline, Week12 | The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome. The function dimension asks about the degree of difficulty in doing 17 activities due to the reference joint. The score ranges from 0 to 170. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Matching placebo of 2.0 mL for IA injection | 140 |
| CNTX-4975-05 (Trans-capsaicin) Pre-filled glass syringes administered as a single 2.0 mL IA injection | 184 |
| Total | 324 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 3 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Lack of Efficacy | 9 | 12 |
| Overall Study | Lost to Follow-up | 7 | 3 |
| Overall Study | Protocol Violation | 3 | 5 |
| Overall Study | Withdrawal by Subject | 8 | 15 |
| Overall Study | WITHDRAWAL FOR OTHER TREATMENT; UNABLE TO COMPLETE INJECTION PROCEDURES | 4 | 13 |
Baseline characteristics
| Characteristic | Placebo | CNTX-4975-05 (Trans-capsaicin) | Total |
|---|---|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 8.59 | 62.8 years STANDARD_DEVIATION 8.8 | 62.8 years STANDARD_DEVIATION 8.7 |
| Average Weekly Pain with Walking NPRS (0-10) Score | 6.933 score on a scale STANDARD_DEVIATION 1.021 | 7.013 score on a scale STANDARD_DEVIATION 0.995 | 6.978 score on a scale STANDARD_DEVIATION 1.0055 |
| Body Mass Index (kg/m^2) | 32.40 kg/m^2 STANDARD_DEVIATION 5.265 | 32.37 kg/m^2 STANDARD_DEVIATION 5.895 | 32.38 kg/m^2 STANDARD_DEVIATION 5.623 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 37 Participants | 56 Participants | 93 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 103 Participants | 128 Participants | 231 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 37 Participants | 49 Participants | 86 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 97 Participants | 131 Participants | 228 Participants |
| Sex: Female, Male Female | 84 Participants | 115 Participants | 199 Participants |
| Sex: Female, Male Male | 56 Participants | 69 Participants | 125 Participants |
| Study Baseline WOMAC A (Pain) Domain Score (range 0-50) | 31.3 score on a scale STANDARD_DEVIATION 7.2 | 31.6 score on a scale STANDARD_DEVIATION 7.36 | 31.5 score on a scale STANDARD_DEVIATION 7.28 |
| Study Baseline WOMAC B (Stiffness) Domain Score (range 0-20) | 13.2 score on a scale STANDARD_DEVIATION 3.41 | 13.2 score on a scale STANDARD_DEVIATION 3.15 | 13.2 score on a scale STANDARD_DEVIATION 3.26 |
| Study Baseline WOMAC C (Function) Domain Score (range 0-170) | 107.9 score on a scale STANDARD_DEVIATION 26.71 | 109.5 score on a scale STANDARD_DEVIATION 25.89 | 108.8 score on a scale STANDARD_DEVIATION 26.22 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 140 | 2 / 184 |
| other Total, other adverse events | 34 / 140 | 70 / 184 |
| serious Total, serious adverse events | 9 / 140 | 9 / 184 |
Outcome results
Primary
Mean Change From Baseline in WOMAC A (Pain) Dimension
The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome. The pain dimension includes 5 items about the amount of pain experienced doing various activities (walking, stair climbing, nocturnal, at rest, weight bearing). The score ranges from 0 to 50.
Time frame: Baseline, Week 12
Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in WOMAC A (Pain) Dimension | -14.13 score on a scale | Standard Deviation 12.217 |
| CNTX-4975-05 | Mean Change From Baseline in WOMAC A (Pain) Dimension | -17.16 score on a scale | Standard Deviation 12.266 |
Comparison: The MMRM analysis included the change from study baseline in scores as the dependent variable, with terms for treatment, pooled study center, study baseline K-L grade category for the index knee, study baseline BMI category, study baseline OA type (unilateral or bilateral knee OA), sex, study visit, treatment by visit interaction, and study baseline score as covariates, using an unstructured covariance structure.p-value: 0.083395% CI: [-4.42, 0.27]Mixed Models Analysis
Secondary
Change From Baseline in Average Weekly Pain With Walking (NPRS 0-10) in the Index Knee
Average daily OA pain in the index knee while walking was evaluated using a 0 to 10 Numerical Pain Rating Scale (NPRS) (0 = no pain and 10 = worst possible pain). 0 was the best score and 10 was the worst score. Subjects used an ePRO at bedtime (9:00 PM ± 3 hours) to record on a daily basis their average daily OA knee pain score with walking during the previous 24 hours.
Time frame: Baseline, Week 12
Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data as collected in the daily diary
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Average Weekly Pain With Walking (NPRS 0-10) in the Index Knee | -2.99 score on a scale | Standard Error 0.213 |
| CNTX-4975-05 | Change From Baseline in Average Weekly Pain With Walking (NPRS 0-10) in the Index Knee | -3.41 score on a scale | Standard Error 0.197 |
Comparison: The MMRM analysis included the change from study baseline in scores as the dependent variable, with terms for treatment, pooled study center, study baseline K-L grade category for the index knee, study baseline BMI category, study baseline OA type (unilateral or bilateral knee OA), sex, study visit, treatment by visit interaction, and study baseline score as covariates, using an unstructured covariance structure.p-value: 0.093595% CI: [-0.91, 0.07]Mixed Models Analysis
Secondary
Mean Change From Study Baseline in WOMAC B (Stiffness) Dimension
The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome. The stiffness dimension has 2 items: joint stiffness upon wakening and joint stiffness later in the day. The score ranges from 0 to 20.
Time frame: Baseline, Week 12
Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Study Baseline in WOMAC B (Stiffness) Dimension | -5.36 score on a scale | Standard Error 0.434 |
| CNTX-4975-05 | Mean Change From Study Baseline in WOMAC B (Stiffness) Dimension | -6.58 score on a scale | Standard Error 0.404 |
Comparison: The MMRM analysis included the change from study baseline in scores as the dependent variable, with terms for treatment, pooled study center, study baseline K-L grade category for the index knee, study baseline BMI category, study baseline OA type (unilateral or bilateral knee OA), sex, study visit, treatment by visit interaction, and study baseline score as covariates, using an unstructured covariance structure.p-value: 0.016395% CI: [-2.22, -0.23]Mixed Models Analysis
Secondary
Mean Change From Study Baseline in WOMAC C (Function) Dimension
The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome. The function dimension asks about the degree of difficulty in doing 17 activities due to the reference joint. The score ranges from 0 to 170.
Time frame: Baseline, Week12
Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Study Baseline in WOMAC C (Function) Dimension | -49.03 score on a scale | Standard Error 3.541 |
| CNTX-4975-05 | Mean Change From Study Baseline in WOMAC C (Function) Dimension | -57.02 score on a scale | Standard Error 3.307 |
Comparison: The MMRM analysis included the change from study baseline in scores as the dependent variable, with terms for treatment, pooled study center, study baseline K-L grade category for the index knee, study baseline BMI category, study baseline OA type (unilateral or bilateral knee OA), sex, study visit, treatment by visit interaction, and study baseline score as covariates, using an unstructured covariance structure.p-value: 0.050995% CI: [-16.01, 0.03]Mixed Models Analysis