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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Breg Cooling Control Group | Experimental | Subject receives 2% lidocaine and CNTX-4975-05 with cooling device Breg ice water pump. |
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| Gel Pack Cooling Group | Experimental | Subject receives 2% lidocaine and CNTX-4975-05 with cooling device Elasto-Gel. |
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| Shortened Gel Pack Cooling Group | Experimental | Subject receives 2% lidocaine and CNTX-4975-05 with cooling device Elasto-Gel. |
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| Single Needle Injection Gel Pack Cooling Group - 2% Lidocaine | Experimental | Subject receives 2% lidocaine and CNTX-4975-05 with cooling device Elasto-Gel. |
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| Single Needle Injection Gel Pack Cooling Group - 1% Lidocaine | Experimental | Subject receives 1% lidocaine and CNTX-4975-05 with cooling device Elasto-Gel. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CNTX-4975-05 | Drug | Osteoarthritis (OA) intra-articular injection of CNTX-4975-05 |
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| Measure | Description | Time Frame |
|---|---|---|
| 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). | Day 1 assessments |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Key Inclusion Criteria:
These subjects may have:
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.
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Randall M. Stevens, MD | Centrexion Therapeutics Corp | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alabama Orthopaedic Center-Research | Birmingham | Alabama | 35209 | United States | ||
| Holland Center for Family Health |
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Subjects were recruited between 18 September 2018 and 22 October 2019
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1. Breg Cooling Control | Breg Cooler (total cool time at least 85 minutes) with IA injection of 2% lidocaine followed by a second IA injection CNTX-4975 |
| FG001 | Group 2. Gel Pack Cooling |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 13, 2019 |
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| Lidocaine without epinephrine | Drug | 15 mL lidocaine intra-articular injection |
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| ElastoGel | Device | Cooling Device |
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| Breg Ice Water Pump | Device | Cooling Device |
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| Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| 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. | Baseline, Week 8 |
| 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 | Baseline, Week 8 |
| Peoria |
| Arizona |
| 85381 |
| United States |
| Noble Clinical Research | Tucson | Arizona | 85704 | United States |
| Med Center Medical Clinic | Carmichael | California | 95608 | United States |
| Core Healthcare Group | Cerritos | California | 90703 | United States |
| Encompass Clinical Research | Spring Valley | California | 91978 | United States |
| Chase Medical Research, LLC | Waterbury | Connecticut | 06708 | United States |
| Conquest Clinical Research | Maitland | Florida | 32751 | United States |
| F&T Medical Research, Inc. | Miami | Florida | 33184 | United States |
| M&M Medical Center, Inc. | Miami | Florida | 33185 | United States |
| Charter Research | Mt. Dora | Florida | 32757 | United States |
| Premier MED Family & Sports Medicine | Ocoee | Florida | 34761 | United States |
| Ascension Research | Pinellas Park | Florida | 33781 | United States |
| M&M Clinical Trials Sunrise | Sunrise | Florida | 33351 | United States |
| Georgia Institute for Clinical Research, LLC | Marietta | Georgia | 30060 | United States |
| Atlanta Orthopaedic Institute, LLC | Stockbridge | Georgia | 30281 | United States |
| Healthcare Research Network II, LLC | Flossmoor | Illinois | 60422 | United States |
| Affinity Health | Oak Brook | Illinois | 60523 | United States |
| MediSphere Medical Research Center, LLC | Evansville | Indiana | 47714 | United States |
| Tandem Clinical Research | Marrero | Louisiana | 70072 | United States |
| DelRicht Research | New Orleans | Louisiana | 70115 | United States |
| Healthcare Research Network | Hazelwood | Missouri | 63042 | United States |
| Center for Pharmaceutical Research, LLC | Kansas City | Missouri | 64114 | United States |
| Office of Robert P. Kaplan, DO | Las Vegas | Nevada | 89119 | United States |
| Hassman Research Institute | Berlin | New Jersey | 08009 | United States |
| First Surgical Hospital | Bellaire | Texas | 77401 | United States |
| Metroplex Clinical Research Center | Dallas | Texas | 75231 | United States |
| Hermann Drive Surgical Hospital | Houston | Texas | 77004 | United States |
Gel Pack Cooling (total cool time at least 60 minutes) with IA injection of 2% lidocaine followed by a second IA injection CNTX-4975
| FG002 | Group 3. Shortened Gel Pack Cooling | Gel pack cooling (total cool time at least 35 minutes) with IA injection of 2% lidocaine followed by a second IA injection CNTX-4975 |
| FG003 | Group 4. Single Needle Injection Gel Pack Cooling - 2% Lidocaine | Gel pack cooling (total cool time at least 45 minutes) with a combined single IA injection of 2% lidocaine followed by CNTX-4975 |
| FG004 | Group 5. Single Needle Injection Gel Pack Cooling - 1% Lidocaine | Gel pack cooling (total cool time at least 45 minutes) with a combined single IA injection of 1% lidocaine followed by CNTX-4975 |
| Treated |
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| COMPLETED |
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| NOT COMPLETED |
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Safety Population, all subjects who received any amount of CNTX-4975-05
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Body Mass Index (kg/m^2) | Mean | Standard Deviation | kg/m^2 |
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| Radiographic Osteoarthritis Type | Count of Participants | Participants |
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| Subject Type | Count of Participants | Participants |
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| KOOS Pain Subscale (Index Knee) | 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). Higher scores indicate better outcome. | Mean | Standard Deviation | score on a scale |
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| KOOS Symptoms Subscale (Index Knee) | 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). Higher scores indicate better outcome. | Mean | Standard Deviation | score on a scale |
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| KOOS Function (Daily Living) Subscale (Index Knee) | 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). Higher scores indicate better outcome. | Mean | Standard Deviation | score on a scale |
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| KOOS Function (Sport and Recreational Activities) Subscale (Index Knee) | 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). Higher scores indicate better outcome. | Mean | Standard Deviation | score on a scale |
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| KOOS Quality of Life Subscale (Index Knee) | 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). Higher scores indicate better outcome. | Mean | Standard Deviation | score on a scale |
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| Pain with Walking NPRS (0-10) Score | 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. Lower scores indicate less pain, higher scores indicate higher pain. | Mean | Standard Deviation | score on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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). | 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. | Posted | Geometric Least Squares Mean | Standard Error | score on a scale | Day 1 assessments |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 8 |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 8 |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 8 |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 8 |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 8 |
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| 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. | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 8 |
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| 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 | 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. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline, Week 8 |
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Adverse events were collected from Screening to the End of the Study (8 Weeks)
Adverse events are reported here according to bilateral or unilateral injection group. Adverse events by injection group is of greater safety consequence and interest than events by cooling regimens because the injection group delineates exposures to CNTX-4975-05 (index knee only or bilateral intra-articular injections) while the cooling regimens does not. Therefore representing adverse events by injection group is a better indicator of safety in relation to study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Single Knee Injection (Unilateral Mod-Sev OA Knee Pain) Day 1 Through Week 8/Early Termination | Subjects with moderate to severe OA knee pain in the index knee and mild to no pain in the non-index knee; TEAEs presented for subjects in the Single Knee Injection groups represents TEAEs occurring from Day 1 through Week 8/Early Termination | 0 | 273 | 1 | 273 | 33 | 273 |
| EG001 | Single Knee Injection (Non-Index Knee PJR/TJR) Day 1 Through Week 8/Early Termination | Single Knee Injection (Non-index Knee partial or total joint replacement) Data presented for subjects in the Single Knee Injection groups represents TEAEs occurring from Day 1 through Week 8/Early Termination | 0 | 52 | 0 | 52 | 11 | 52 |
| EG002 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) Day 1 Through Day 7 | Subjects with moderate to severe knee OA pain in both the index and non-index knee; TEAEs presented for subjects in the Bilateral Knee Injection group only from Day 1 (index knee) through Day 7 (i.e., prior to them receiving the second intra-articular injection of CNTX-4975) | 0 | 523 | 0 | 523 | 18 | 523 |
| EG003 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) Day 7 Through Week 8/Early Termination | Subjects with moderate to severe knee OA pain in both the index and non-index knee that received bilateral injections of CNTX-4975; TEAEs presented for subjects in the Bilateral Knee Injection group from Day 8 (i.e., after receiving the second injection of CNTX-4975 into the nonindex knee) to Week 8/Early Termination. Note: 96 subjects did not receive a second injection of CNTX-4975 | 0 | 427 | 5 | 427 | 27 | 427 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MEDRA | Systematic Assessment |
| |
| Atrial Fibrillation | Cardiac disorders | MEDRA | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MEDRA | Systematic Assessment |
| |
| Staphylococcal Infection | Infections and infestations | MEDRA | Systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MEDRA | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MEDRA | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Back Pain | Musculoskeletal and connective tissue disorders | MEDRA | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MEDRA | Systematic Assessment |
| |
| Joint Swelling | Musculoskeletal and connective tissue disorders | MEDRA | Systematic Assessment |
| |
| Muscle Spasm | Musculoskeletal and connective tissue disorders | MEDRA | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MEDRA | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MEDRA | Systematic Assessment |
| |
| Abdominal Upper Pain | Gastrointestinal disorders | MEDRA | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MEDRA | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MEDRA | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MEDRA | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MEDRA | Systematic Assessment |
| |
| Upper Respiratory tract infectiosn | Infections and infestations | MEDRA | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MEDRA | Systematic Assessment |
| |
| Urinary Track Infection | Infections and infestations | MEDRA | Systematic Assessment |
| |
| Ligament Sprain | Injury, poisoning and procedural complications | MEDRA | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MEDRA | Systematic Assessment |
| |
| Puritus | Skin and subcutaneous tissue disorders | MEDRA | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MEDRA | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MEDRA | Systematic Assessment |
| |
| Alanine aminotransferase | Investigations | MEDRA | Systematic Assessment |
| |
| Blood creatine increased | Investigations | MEDRA | Systematic Assessment |
| |
| Headache | Nervous system disorders | MEDRA | Systematic Assessment |
| |
| Tooth extraction | Vascular disorders | MEDRA | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MEDRA | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MEDRA | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Operations | Centrexion Therapeutics Corporation | 617-837-6911 | info@centrexion.com |
| Dec 23, 2021 |
| Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D020370 | Osteoarthritis, Knee |
| D010003 | Osteoarthritis |
| D010146 | Pain |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D002211 | Capsaicin |
| D008012 | Lidocaine |
| D004837 | Epinephrine |
| ID | Term |
|---|---|
| D053284 | Polyunsaturated Alkamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000475 | Alkenes |
| D006839 | Hydrocarbons, Acyclic |
| D006838 | Hydrocarbons |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D005229 | Fatty Acids, Monounsaturated |
| D005231 | Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D002395 | Catecholamines |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Bilateral |
|
| Single knee Injection (Non-Index knee PJR/TJR) |
|
| Bilateral Knee Injections (Bilateral mod-Sec OA Knee Pain) |
|
| OG004 | 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. |
| Non-Inferiority |
The treatment regimen is Clinically Acceptable if it is no more than 30% worse than the Breg Cooling Control Group and the lower bound of the 95% CI for Ratio of Geometric LS Means is greater than 0.7. |
| 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. | Ratio of Geometric LS Means | 0.959 | Standard Error of the Mean | 1.0221 | 2-Sided | 95 | 0.919 | 1.001 | Parameter dispersion is the Standard Error of the Ratio of Geometric LS Means | Non-Inferiority | The treatment regimen is Clinically Acceptable if it is no more than 30% worse than the Breg Cooling Control Group and the lower bound of the 95% CI for Ratio of Geometric LS Means is greater than 0.7. |
| 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. | Ratio of Geometric LS Means | 1.013 | Standard Error of the Mean | 1.0219 | 2-Sided | 95 | 0.970 | 1.057 | Parameter dispersion is the Standard Error of the Ratio of Geometric LS Means | Non-Inferiority | The treatment regimen is Clinically Acceptable if it is no more than 30% worse than the Breg Cooling Control Group and the lower bound of the 95% CI for Ratio of Geometric LS Means is greater than 0.7. |
| 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. | Ratio of Geometric LS Means | 0.931 | Standard Error of the Mean | 1.0219 | 2-Sided | 95 | 0.892 | 0.972 | Parameter dispersion is the Standard Error of the Ratio of Geometric LS Means | Non-Inferiority | The treatment regimen is Clinically Acceptable if it is no more than 30% worse than the Breg Cooling Control Group and the lower bound of the 95% CI for Ratio of Geometric LS Means is greater than 0.7. |
Subjects with single knee OA pain in the index knee and a partial or total knee joint replacement in the non-index knee; results reported for index knee
| OG002 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee; results reported for the index knee in these subjects |
| OG003 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) NON-INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee that received bilateral injections of CNTX-4975; results reported for the non-index knee in these subjects |
|
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Subjects with single knee OA pain in the index knee and a partial or total knee joint replacement in the non-index knee; results reported for index knee
| OG002 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee; results reported for the index knee in these subjects |
| OG003 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) NON-INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee that received bilateral injections of CNTX-4975; results reported for the non-index knee in these subjects |
|
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Subjects with single knee OA pain in the index knee and a partial or total knee joint replacement in the non-index knee; results reported for index knee |
| OG002 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee; results reported for the index knee in these subjects |
| OG003 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) NON-INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee that received bilateral injections of CNTX-4975; results reported for the non-index knee in these subjects |
|
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|
Subjects with single knee OA pain in the index knee and a partial or total knee joint replacement in the non-index knee; results reported for index knee
| OG002 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee; results reported for the index knee in these subjects |
| OG003 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) NON-INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee that received bilateral injections of CNTX-4975; results reported for the non-index knee in these subjects |
|
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|
Subjects with single knee OA pain in the index knee and a partial or total knee joint replacement in the non-index knee; results reported for index knee
| OG002 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee; results reported for the index knee in these subjects |
| OG003 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) NON-INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee that received bilateral injections of CNTX-4975; results reported for the non-index knee in these subjects |
|
|
|
Subjects with single knee OA pain in the index knee and a partial or total knee joint replacement in the non-index knee; results reported for index knee
| OG002 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee; results reported for the index knee in these subjects |
| OG003 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) NON-INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee that received bilateral injections of CNTX-4975; results reported for the non-index knee in these subjects |
|
|
|
Subjects with moderate to severe knee OA pain in both the index and non-index knee; results reported for the index knee in these subjects |
| OG003 | Bilateral Knee Injection (Bilateral Mod-Sev OA Knee Pain) NON-INDEX KNEE | Subjects with moderate to severe knee OA pain in both the index and non-index knee that received bilateral injections of CNTX-4975; results reported for the non-index knee in these subjects |
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