Knee Osteoarthritis
Conditions
Keywords
osteoarthritis, knee pain, non opioid, analgesic, capsaicin, pain, intra-articular
Brief summary
An Open-label, 8-Week Study to Compare the Comfort and Ease of Use of Five Different Treatment Regimens for CNTX 4975-05 Intra-articular Injection in Subjects with Chronic, Moderate-to-Severe Osteoarthritis Knee Pain.
Detailed description
This is an open-label, single injection (per knee), 8-week study to evaluate the comfort and ease of use of 5 different treatment regimens, and to evaluate the efficacy and safety of a single intra-articular (IA) injection, in one or both knees, of CNTX-4975-05 in subjects with chronic, moderate-to-severe knee OA pain. Procedural pain associated with IA injection of the investigational product, CNTX-4975-05, will be controlled primarily through adjunct controlled joint cooling and secondarily by pre-medication with IA lidocaine.
Interventions
DRUGCNTX-4975-05
Osteoarthritis (OA) intra-articular injection of CNTX-4975-05
DRUGLidocaine without epinephrine
15 mL lidocaine intra-articular injection
DEVICEElastoGel
Cooling Device
DEVICEBreg Ice Water Pump
Cooling Device
Sponsors
Centrexion Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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) * Confirmation of osteoarthritis (OA) of the knee: radiography of both knees using standard standing films (scored by the investigator) or using the fixed flexion method, taken during the Screening Visit of CNTX-4975i-OA-301 or CNTX-4975i-OA-304. * Confirmation of OA of the index knee: American College of Rheumatology (ACR) diagnostic criteria * For subjects for monoarticular knee injection, the index knee must have moderate to severe pain at screening associated with OA, which must be stable for a minimum of 6 months prior to Screening, as assessed by the investigator. These subjects may have: 1. unilateral or bilateral OA, with the index knee having moderate to severe pain, and the contralateral knee having none to mild pain, OR 2. unilateral or bilateral OA, with the index knee having moderate to severe pain and the other knee having had a PJR or TJR within 5 years of the Screening Visit. The knee with the PJR/TJR is not to be injected with CNTX-4975-05. For subjects for bilateral knee injection, the index knee must have moderate to severe pain at screening associated with OA, and greater pain in the index knee than in the contralateral knee. Their pain must be stable for a minimum of 6 months prior to Screening, as assessed by the investigator. The index knee in these subjects is the one with the worst pain with walking. Where both knees have equal pain with walking, then the knee on the subject's dominant side will be designated the index knee. For qualifying knee pain with walking, subjects will use an NPRS (0-10; 0=no pain, 10=worst possible pain) to rate their knee pain with walking (both knees, except knees with PJR/TJR). The PJR/TJR pain should be rated using the NPRS scale, but will not be a qualifying pain score. * Body mass index ≤45 kg/m\^2. Key
Exclusion criteria
* Joint replacement surgery of the index knee at any time, or open surgery of the index knee in the past 24 months. Joint replacement of the contralateral knee is permitted for subjects who will not receive an injection in the contralateral (natural) knee. * 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 OA. Radicular or referred pain involving the index knee or from joint disease other than OA involving the index knee, such as, but not restricted to chondromalacia patellae, inflammatory disease, metabolic diseases, gout/pseudogout, hemochromatosis, acromegaly, etc. * Periarticular pain from any cause, including referred pain, bursitis, tendonitis, soft tissue tenderness, or subacute/acute pain from injury. * Other chronic pain anywhere in the body that requires the use of chronic analgesic medications, including, but not limited to, local painful areas, myofascial pain syndromes, fibromyalgia, genetic, metabolic abnormalities, hematologic, or neuropathic pain.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of Optimal Procedure for Administering CNTX-4975-05 With Regards to Pain, Participant Satisfaction, and Investigator's Satisfaction | Day 1 assessments | A composite score was calculated for each of the 5 treatment regimens by summing the scores of three assessments: (1) procedure pain 30 minutes after injection of CNTX-4975-05 on a 0-4 scale, 0 was best indicating no procedure pain, 4 was worst indicating severe procedure pain; (2) assessment of subjects' satisfaction with the regimen on a scale of 1 (completely dissatisfied) to 7 (completely satisfied), 1 was worst and 7 was best; and (3) assessment of investigators' satisfaction with the regimen on a scale of 1 (completely dissatisfied) to 7 (completely satisfied), 1 was worst and 7 was best. The procedure pain at 30 minutes was reversed to a 1-7 scale so 7 was best indicating no procedure pain and 1 was worst indicating severe procedure pain. The three assessments were summed for a total score from 3-21, 3 being the worst outcome and 21 being the best outcome. The geometric mean of the scores was derived for each group. All assessments were administered on Day 1 (Baseline). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in KOOS Pain Subscale Score by Subject Type | Baseline, Week 8 | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related Quality of Life. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. |
| Mean Change From Baseline in KOOS Pain With Walking Single Question Score by Subject Type | Baseline, Week 8 | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related Quality of Life. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS Pain with Walking is a single question from the KOOS Pain subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. |
| Mean Change From Baseline in KOOS Function (Daily Living) Subscale Score by Subject Type | Baseline, Week 8 | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related QOL. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. |
| Mean Change From Baseline in KOOS Symptoms Subscale Score by Subject Type | Baseline, Week 8 | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related Quality of Life. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. |
| Mean Change From Baseline in KOOS Knee-Related Quality of Life Subscale Score by Subject Type | Baseline, Week 8 | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related QOL. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. |
| Mean Change From Baseline in Average Daily Pain With Walking NPRS (0-10) Score by Subject Type | Baseline, Week 8 | The pain with walking Numerical Pain Rating Scale (NPRS) (0-10, 0 being no pain, 10 being greatest pain) collected subjects' average pain with walking over the past 24 hours. Subjects recorded the pain in their target knee, either the index knee or additionally the non-index knee in the case of bilateral subjects. The NPRS was collected at Day 1 (Baseline) and Week 8. Lower scores (or negative change from baseline) indicate improvement |
| Mean Change From Baseline in KOOS Function (Sport and Recreational Activities) Subscale Score by Subject Type | Baseline, Week 8 | The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related QOL. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited between 18 September 2018 and 22 October 2019
Participants by arm
| Arm | Count |
|---|---|
| Group 1. Breg Cooling Control The subject received intra-articular injections from separate needles of 2% lidocaine without epinephrine followed by CNTX-4975-05 15 minutes later. The subject was cooled with the Breg ice water pump and circumferential knee wrap for 15 minutes before lidocaine injection, followed by 30 minutes before the CNTX-4975-05 injection, and for at least 30 minutes and up to 90 minutes after the CNTX-4975-05 injection as needed. | 162 |
| Group 2. Gel Pack Cooling The subject received intra-articular injections from separate needles of 2% lidocaine without epinephrine followed by CNTX-4975-05 10 minutes later. The subject was cooled with the Elasto-Gel circumferential knee wrap for 40 minutes before the lidocaine injection, followed by 10 minutes before the CNTX-4975-05 injection, and for at least 10 minutes and up to 90 minutes after the CNTX-4975-05 injection as needed. | 179 |
| Group 3. Shortened Gel Pack Cooling The subject received intra-articular injections from separate needles of 2% lidocaine without epinephrine followed by CNTX-4975-05 5 minutes later. The subject was cooled with the Elasto-Gel circumferential knee wrap for 30 minutes before the lidocaine injection, followed by 5 minutes before the CNTX-4975-05 injection, and with no required cooling after the CNTX-4975-05 injection, but up to 90 minutes of cooling as needed. | 175 |
| Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine The subject received intra-articular injections from a single needle of 2% lidocaine without epinephrine and CNTX-4975-05, with up to 3 minutes in between injections. The subject was cooled with the Elasto-Gel circumferential knee wrap for 45 minutes before the single needle injection of lidocaine and CNTX-4975-05. There was no cooling in between injections and no cooling required after the single needle injections, but up to 90 minutes of cooling as needed. | 160 |
| Group 5. Single Needle Injection Gel Pack Cooling - 1% Lidocaine The subject received intra-articular injections from a single needle of 1% lidocaine without epinephrine and CNTX-4975-05, with up to 3 minutes in between injections. The subject was cooled with the Elasto-Gel circumferential knee wrap for 45 minutes before the single needle injection of lidocaine and CNTX-4975-05. There was no cooling in between injections and no cooling required after the single needle injections, but up to 90 minutes of cooling as needed. | 172 |
| Total | 848 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 5 | 1 | 2 | 2 | 6 |
| Overall Study | Other | 1 | 1 | 1 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 1 | 1 | 2 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Sponsors Decision | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 5 | 1 | 7 | 7 |
Baseline characteristics
| Characteristic | Group 1. Breg Cooling Control | Total | Group 5. Single Needle Injection Gel Pack Cooling - 1% Lidocaine | Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine | Group 3. Shortened Gel Pack Cooling | Group 2. Gel Pack Cooling |
|---|---|---|---|---|---|---|
| Age, Continuous | 62.2 Years STANDARD_DEVIATION 9.5 | 63.1 Years STANDARD_DEVIATION 9.4 | 65.1 Years STANDARD_DEVIATION 9.9 | 62.6 Years STANDARD_DEVIATION 9.4 | 63.9 Years STANDARD_DEVIATION 9.2 | 61.8 Years STANDARD_DEVIATION 8.8 |
| Body Mass Index (kg/m^2) | 31.21 kg/m^2 STANDARD_DEVIATION 5.349 | 31.25 kg/m^2 STANDARD_DEVIATION 6.252 | 31.72 kg/m^2 STANDARD_DEVIATION 6.099 | 31.54 kg/m^2 STANDARD_DEVIATION 6.083 | 31.89 kg/m^2 STANDARD_DEVIATION 7.904 | 29.94 kg/m^2 STANDARD_DEVIATION 5.276 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 69 Participants | 196 Participants | 7 Participants | 17 Participants | 15 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 93 Participants | 651 Participants | 164 Participants | 143 Participants | 160 Participants | 91 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| KOOS Function (Daily Living) Subscale (Index Knee) | 46.42 score on a scale STANDARD_DEVIATION 13.586 | 48.55 score on a scale STANDARD_DEVIATION 14.607 | 47.05 score on a scale STANDARD_DEVIATION 14.511 | 48.87 score on a scale STANDARD_DEVIATION 14.535 | 52.50 score on a scale STANDARD_DEVIATION 15.846 | 47.81 score on a scale STANDARD_DEVIATION 13.791 |
| KOOS Function (Sport and Recreational Activities) Subscale (Index Knee) | 25.06 score on a scale STANDARD_DEVIATION 18.485 | 27.12 score on a scale STANDARD_DEVIATION 21.747 | 30.74 score on a scale STANDARD_DEVIATION 24.279 | 30.66 score on a scale STANDARD_DEVIATION 23.312 | 26.29 score on a scale STANDARD_DEVIATION 21.98 | 23.44 score on a scale STANDARD_DEVIATION 19.417 |
| KOOS Pain Subscale (Index Knee) | 42.42 score on a scale STANDARD_DEVIATION 12.959 | 44.97 score on a scale STANDARD_DEVIATION 13.83 | 44.33 score on a scale STANDARD_DEVIATION 14.201 | 44.70 score on a scale STANDARD_DEVIATION 12.803 | 48.30 score on a scale STANDARD_DEVIATION 15.071 | 44.89 score on a scale STANDARD_DEVIATION 13.397 |
| KOOS Quality of Life Subscale (Index Knee) | 31.98 score on a scale STANDARD_DEVIATION 16.387 | 31.83 score on a scale STANDARD_DEVIATION 17.313 | 27.54 score on a scale STANDARD_DEVIATION 16.62 | 32.93 score on a scale STANDARD_DEVIATION 18.248 | 30.24 score on a scale STANDARD_DEVIATION 16.751 | 36.31 score on a scale STANDARD_DEVIATION 17.45 |
| KOOS Symptoms Subscale (Index Knee) | 47.69 score on a scale STANDARD_DEVIATION 16.611 | 50.26 score on a scale STANDARD_DEVIATION 16.348 | 51.73 score on a scale STANDARD_DEVIATION 16.227 | 47.97 score on a scale STANDARD_DEVIATION 14.484 | 52.75 score on a scale STANDARD_DEVIATION 17.57 | 50.86 score on a scale STANDARD_DEVIATION 16.161 |
| Pain with Walking NPRS (0-10) Score | 7.58 score on a scale STANDARD_DEVIATION 1.413 | 7.05 score on a scale STANDARD_DEVIATION 1.467 | 6.91 score on a scale STANDARD_DEVIATION 1.367 | 6.83 score on a scale STANDARD_DEVIATION 1.493 | 6.70 score on a scale STANDARD_DEVIATION 1.585 | 7.23 score on a scale STANDARD_DEVIATION 1.311 |
| Radiographic Osteoarthritis Type Bilateral | 153 Participants | 693 Participants | 122 Participants | 138 Participants | 144 Participants | 136 Participants |
| Radiographic Osteoarthritis Type Unilateral | 9 Participants | 155 Participants | 50 Participants | 22 Participants | 31 Participants | 43 Participants |
| Sex: Female, Male Female | 104 Participants | 508 Participants | 100 Participants | 99 Participants | 104 Participants | 101 Participants |
| Sex: Female, Male Male | 58 Participants | 340 Participants | 72 Participants | 61 Participants | 71 Participants | 78 Participants |
| Subject Type Bilateral Knee Injections (Bilateral mod-Sec OA Knee Pain) | 133 Participants | 523 Participants | 87 Participants | 94 Participants | 92 Participants | 117 Participants |
| Subject Type Single knee Injection (Non-Index knee PJR/TJR) | 3 Participants | 52 Participants | 16 Participants | 9 Participants | 12 Participants | 12 Participants |
| Subject Type Single Knee Injection (Unilateral Mod-Sec OA Knee Pain) | 26 Participants | 273 Participants | 69 Participants | 57 Participants | 71 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 273 | 0 / 52 | 0 / 523 | 0 / 427 |
| other Total, other adverse events | 33 / 273 | 11 / 52 | 18 / 523 | 27 / 427 |
| serious Total, serious adverse events | 1 / 273 | 0 / 52 | 0 / 523 | 5 / 427 |
Outcome results
Primary
Determination of Optimal Procedure for Administering CNTX-4975-05 With Regards to Pain, Participant Satisfaction, and Investigator's Satisfaction
A composite score was calculated for each of the 5 treatment regimens by summing the scores of three assessments: (1) procedure pain 30 minutes after injection of CNTX-4975-05 on a 0-4 scale, 0 was best indicating no procedure pain, 4 was worst indicating severe procedure pain; (2) assessment of subjects' satisfaction with the regimen on a scale of 1 (completely dissatisfied) to 7 (completely satisfied), 1 was worst and 7 was best; and (3) assessment of investigators' satisfaction with the regimen on a scale of 1 (completely dissatisfied) to 7 (completely satisfied), 1 was worst and 7 was best. The procedure pain at 30 minutes was reversed to a 1-7 scale so 7 was best indicating no procedure pain and 1 was worst indicating severe procedure pain. The three assessments were summed for a total score from 3-21, 3 being the worst outcome and 21 being the best outcome. The geometric mean of the scores was derived for each group. All assessments were administered on Day 1 (Baseline).
Time frame: Day 1 assessments
Population: The intent to treat (ITT) population included all enrolled subjects who received any amount of CNTX-4975-05. A subject was considered enrolled if they had a Treatment Day 1 study visit.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1. Breg Cooling Control | Determination of Optimal Procedure for Administering CNTX-4975-05 With Regards to Pain, Participant Satisfaction, and Investigator's Satisfaction | 17.18 score on a scale | Standard Error 1.016 |
| Group 2. Gel Pack Cooling | Determination of Optimal Procedure for Administering CNTX-4975-05 With Regards to Pain, Participant Satisfaction, and Investigator's Satisfaction | 18.26 score on a scale | Standard Error 1.015 |
| Group 3. Shortened Gel Pack Cooling | Determination of Optimal Procedure for Administering CNTX-4975-05 With Regards to Pain, Participant Satisfaction, and Investigator's Satisfaction | 16.48 score on a scale | Standard Error 1.016 |
| Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine | Determination of Optimal Procedure for Administering CNTX-4975-05 With Regards to Pain, Participant Satisfaction, and Investigator's Satisfaction | 17.40 score on a scale | Standard Error 1.016 |
| Group 5. Single Needle Injection Gel Pack Cooling - 1% Lidocaine | Determination of Optimal Procedure for Administering CNTX-4975-05 With Regards to Pain, Participant Satisfaction, and Investigator's Satisfaction | 16.00 score on a scale | Standard Error 1.015 |
Comparison: Geometric LS means, ratio of geometric LS means, with Breg Cooling as control, and 95% CIs were obtained from an ANCOVA model on the natural log-transformed composite outcome with cooling and injection procedure as the main effect. Baseline K-L grade, baseline BMI category, sex, and reverse-scored and normalized index knee procedure pain were included as covariates. Estimates and CIs on the log scale were exponentiated to obtain ratios of geometric means on the original scale.95% CI: [1.019, 1.108]
Comparison: Geometric LS means, ratio of geometric LS means, with Breg Cooling as control, and 95% CIs were obtained from an ANCOVA model on the natural log-transformed composite outcome with cooling and injection procedure as the main effect. Baseline K-L grade, baseline BMI category, sex, and reverse-scored and normalized index knee procedure pain were included as covariates. Estimates and CIs on the log scale were exponentiated to obtain ratios of geometric means on the original scale.95% CI: [0.919, 1.001]
Comparison: Geometric LS means, ratio of geometric LS means, with Breg Cooling as control, and 95% CIs were obtained from an ANCOVA model on the natural log-transformed composite outcome with cooling and injection procedure as the main effect. Baseline K-L grade, baseline BMI category, sex, and reverse-scored and normalized index knee procedure pain were included as covariates. Estimates and CIs on the log scale were exponentiated to obtain ratios of geometric means on the original scale.95% CI: [0.97, 1.057]
Comparison: Geometric LS means, ratio of geometric LS means, with Breg Cooling as control, and 95% CIs were obtained from an ANCOVA model on the natural log-transformed composite outcome with cooling and injection procedure as the main effect. Baseline K-L grade, baseline BMI category, sex, and reverse-scored and normalized index knee procedure pain were included as covariates. Estimates and CIs on the log scale were exponentiated to obtain ratios of geometric means on the original scale.95% CI: [0.892, 0.972]
Secondary
Mean Change From Baseline in Average Daily Pain With Walking NPRS (0-10) Score by Subject Type
The pain with walking Numerical Pain Rating Scale (NPRS) (0-10, 0 being no pain, 10 being greatest pain) collected subjects' average pain with walking over the past 24 hours. Subjects recorded the pain in their target knee, either the index knee or additionally the non-index knee in the case of bilateral subjects. The NPRS was collected at Day 1 (Baseline) and Week 8. Lower scores (or negative change from baseline) indicate improvement
Time frame: Baseline, Week 8
Population: The intent to treat (ITT) population included all enrolled subjects who received any amount of CNTX-4975-05. A subject was considered enrolled if they had a Treatment Day 1 study visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1. Breg Cooling Control | Mean Change From Baseline in Average Daily Pain With Walking NPRS (0-10) Score by Subject Type | -3.48 score on a scale | Standard Error 0.191 |
| Group 2. Gel Pack Cooling | Mean Change From Baseline in Average Daily Pain With Walking NPRS (0-10) Score by Subject Type | -3.52 score on a scale | Standard Error 0.416 |
| Group 3. Shortened Gel Pack Cooling | Mean Change From Baseline in Average Daily Pain With Walking NPRS (0-10) Score by Subject Type | -4.02 score on a scale | Standard Error 0.118 |
| Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine | Mean Change From Baseline in Average Daily Pain With Walking NPRS (0-10) Score by Subject Type | -3.72 score on a scale | Standard Error 0.122 |
Comparison: Results are summarized by subject type and the injected knee. The NPRS was collected during the last study visit. Lower scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline pain score as covariates.p-value: <0.000195% CI: [-3.86, -3.1]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The NPRS was collected during the last study visit. Lower scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline pain score as covariates.p-value: <0.000195% CI: [-4.38, -2.67]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The NPRS was collected during the last study visit. Lower scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline pain score as covariates.p-value: <0.000195% CI: [-4.25, -3.79]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The NPRS was collected during the last study visit. Lower scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline pain score as covariates.p-value: <0.000195% CI: [-3.96, -3.48]Mixed Models Analysis
Secondary
Mean Change From Baseline in KOOS Function (Daily Living) Subscale Score by Subject Type
The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related QOL. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement.
Time frame: Baseline, Week 8
Population: The intent to treat (ITT) population included all enrolled subjects who received any amount of CNTX-4975-05. A subject was considered enrolled if they had a Treatment Day 1 study visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1. Breg Cooling Control | Mean Change From Baseline in KOOS Function (Daily Living) Subscale Score by Subject Type | 20.86 score on a scale | Standard Error 1.481 |
| Group 2. Gel Pack Cooling | Mean Change From Baseline in KOOS Function (Daily Living) Subscale Score by Subject Type | 25.66 score on a scale | Standard Error 4.568 |
| Group 3. Shortened Gel Pack Cooling | Mean Change From Baseline in KOOS Function (Daily Living) Subscale Score by Subject Type | 25.57 score on a scale | Standard Error 0.861 |
| Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine | Mean Change From Baseline in KOOS Function (Daily Living) Subscale Score by Subject Type | 22.26 score on a scale | Standard Error 1.058 |
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [17.94, 23.78]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [16.24, 35.09]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [23.88, 27.26]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [24.02, 27.37]Mixed Models Analysis
Secondary
Mean Change From Baseline in KOOS Function (Sport and Recreational Activities) Subscale Score by Subject Type
The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related QOL. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement.
Time frame: Baseline, Week 8
Population: The intent to treat (ITT) population included all enrolled subjects who received any amount of CNTX-4975-05. A subject was considered enrolled if they had a Treatment Day 1 study visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1. Breg Cooling Control | Mean Change From Baseline in KOOS Function (Sport and Recreational Activities) Subscale Score by Subject Type | 25.17 score on a scale | Standard Error 2.248 |
| Group 2. Gel Pack Cooling | Mean Change From Baseline in KOOS Function (Sport and Recreational Activities) Subscale Score by Subject Type | 33.11 score on a scale | Standard Error 5.795 |
| Group 3. Shortened Gel Pack Cooling | Mean Change From Baseline in KOOS Function (Sport and Recreational Activities) Subscale Score by Subject Type | 27.80 score on a scale | Standard Error 1.233 |
| Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine | Mean Change From Baseline in KOOS Function (Sport and Recreational Activities) Subscale Score by Subject Type | 24.80 score on a scale | Standard Error 1.598 |
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [20.74, 29.6]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [21.15, 45.07]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [25.38, 30.23]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [21.66, 27.94]Mixed Models Analysis
Secondary
Mean Change From Baseline in KOOS Knee-Related Quality of Life Subscale Score by Subject Type
The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related QOL. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement.
Time frame: Baseline, Week 8
Population: The intent to treat (ITT) population included all enrolled subjects who received any amount of CNTX-4975-05. A subject was considered enrolled if they had a Treatment Day 1 study visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1. Breg Cooling Control | Mean Change From Baseline in KOOS Knee-Related Quality of Life Subscale Score by Subject Type | 22.10 score on a scale | Standard Error 1.898 |
| Group 2. Gel Pack Cooling | Mean Change From Baseline in KOOS Knee-Related Quality of Life Subscale Score by Subject Type | 16.75 score on a scale | Standard Error 6.255 |
| Group 3. Shortened Gel Pack Cooling | Mean Change From Baseline in KOOS Knee-Related Quality of Life Subscale Score by Subject Type | 21.52 score on a scale | Standard Error 1.062 |
| Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine | Mean Change From Baseline in KOOS Knee-Related Quality of Life Subscale Score by Subject Type | 19.40 score on a scale | Standard Error 1.365 |
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [18.37, 25.84]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [3.84, 29.66]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [19.43, 23.6]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [16.72, 22.09]Mixed Models Analysis
Secondary
Mean Change From Baseline in KOOS Pain Subscale Score by Subject Type
The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related Quality of Life. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement.
Time frame: Baseline, Week 8
Population: The intent to treat (ITT) population included all enrolled subjects who received any amount of CNTX-4975-05. A subject was considered enrolled if they had a Treatment Day 1 study visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1. Breg Cooling Control | Mean Change From Baseline in KOOS Pain Subscale Score by Subject Type | 22.45 score on a scale | Standard Error 1.478 |
| Group 2. Gel Pack Cooling | Mean Change From Baseline in KOOS Pain Subscale Score by Subject Type | 23.90 score on a scale | Standard Error 4.613 |
| Group 3. Shortened Gel Pack Cooling | Mean Change From Baseline in KOOS Pain Subscale Score by Subject Type | 25.62 score on a scale | Standard Error 0.865 |
| Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine | Mean Change From Baseline in KOOS Pain Subscale Score by Subject Type | 22.10 score on a scale | Standard Error 1.053 |
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [19.54, 25.37]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [14.38, 33.42]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [23.92, 27.32]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [20.03, 24.17]Mixed Models Analysis
Secondary
Mean Change From Baseline in KOOS Pain With Walking Single Question Score by Subject Type
The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related Quality of Life. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS Pain with Walking is a single question from the KOOS Pain subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement.
Time frame: Baseline, Week 8
Population: The intent to treat (ITT) population included all enrolled subjects who received any amount of CNTX-4975-05. A subject was considered enrolled if they had a Treatment Day 1 study visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1. Breg Cooling Control | Mean Change From Baseline in KOOS Pain With Walking Single Question Score by Subject Type | 21.08 score on a scale | Standard Error 1.744 |
| Group 2. Gel Pack Cooling | Mean Change From Baseline in KOOS Pain With Walking Single Question Score by Subject Type | 25.26 score on a scale | Standard Error 6.062 |
| Group 3. Shortened Gel Pack Cooling | Mean Change From Baseline in KOOS Pain With Walking Single Question Score by Subject Type | 25.85 score on a scale | Standard Error 1.035 |
| Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine | Mean Change From Baseline in KOOS Pain With Walking Single Question Score by Subject Type | 23.34 score on a scale | Standard Error 1.238 |
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms for pooled site group, baseline K-L grade category, baseline BMI category (\<30 kg/m2, ≥30 kg/m2), sex, study visit, and baseline KOOS subscale score as covariates. Study visit was included in the model as a categorical variable.p-value: <0.000195% CI: [17.6, 24.5]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms for pooled site group, baseline K-L grade category, baseline BMI category (\<30 kg/m2, ≥30 kg/m2), sex, study visit, and baseline KOOS subscale score as covariates. Study visit was included in the model as a categorical variable.p-value: 0.000395% CI: [12.7, 37.8]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms for pooled site group, baseline K-L grade category, baseline BMI category (\<30 kg/m2, ≥30 kg/m2), sex, study visit, and baseline KOOS subscale score as covariates. Study visit was included in the model as a categorical variable.p-value: <0.000195% CI: [23.82, 27.88]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms for pooled site group, baseline K-L grade category, baseline BMI category (\<30 kg/m2, ≥30 kg/m2), sex, study visit, and baseline KOOS subscale score as covariates. Study visit was included in the model as a categorical variable.p-value: <0.000195% CI: [20.91, 25.78]Mixed Models Analysis
Secondary
Mean Change From Baseline in KOOS Symptoms Subscale Score by Subject Type
The KOOS (KOOS = Knee Injury and Osteoarthritis Outcome Score) was developed as an extension of the WOMAC (Western Ontario and McMaster Universities Arthritis Index) to evaluate the dimensions of knee osteoarthritis associated pain and injury. It includes 5 separately scored subscales: Pain, Symptoms (including stiffness), Function (Daily Living), Function (Sports and Recreational Activities), and knee-related Quality of Life. Each subscale score is rated on a 5-point scale (i.e., 0 to 4). The previous week is the time period evaluated when answering the questions. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The KOOS was administered on Day 1 (Baseline) and Week 8. Higher scores (or positive change from baseline) indicate improvement.
Time frame: Baseline, Week 8
Population: The intent to treat (ITT) population included all enrolled subjects who received any amount of CNTX-4975-05.A subject was considered enrolled if they had a Treatment Day 1 study visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Group 1. Breg Cooling Control | Mean Change From Baseline in KOOS Symptoms Subscale Score by Subject Type | 17.15 score on a scale | Standard Error 1.396 |
| Group 2. Gel Pack Cooling | Mean Change From Baseline in KOOS Symptoms Subscale Score by Subject Type | 20.41 score on a scale | Standard Error 3.692 |
| Group 3. Shortened Gel Pack Cooling | Mean Change From Baseline in KOOS Symptoms Subscale Score by Subject Type | 20.05 score on a scale | Standard Error 0.981 |
| Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine | Mean Change From Baseline in KOOS Symptoms Subscale Score by Subject Type | 18.40 score on a scale | Standard Error 1.011 |
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [14.4, 19.9]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [12.79, 28.03]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [18.44, 21.66]Mixed Models Analysis
Comparison: Results are summarized by subject type and the injected knee. The KOOS subscale scores are derived and normalized. Higher scores indicate improvement. Model terms included pooled site group, baseline K-L grade category, baseline BMI category, sex, study visit, and baseline subscale score as covariates.p-value: <0.000195% CI: [16.41, 20.38]Mixed Models Analysis