Trial Outcomes & Findings for A Phase 3 Efficacy and Safety Study of Intra-articular CNTX-4975-05 (Capsaicin) vs Placebo in Subjects With OA Knee Pain (NCT NCT03429049)
NCT ID: NCT03429049
Last Updated: 2022-07-26
Results Overview
Average daily OA pain in the index knee while walking was evaluated using a 0 to 10 Numerical Pain Rating Scale (NPRS) (0 = no pain and 10 = worst possible pain). 0 was the best score and 10 was the worst score. Subjects used an ePRO at bedtime (9:00 PM ± 3 hours) to record on a daily basis their average daily OA knee pain score with walking during the previous 24 hours.
COMPLETED
PHASE3
332 participants
Baseline, Week 12
2022-07-26
Participant Flow
Participant milestones
| Measure |
Placebo
Matching placebo of 2.0 mL for IA injection
|
CNTX-4975-05
Pre-filled glass syringes administered as a single 2.0 mL IA injection
|
|---|---|---|
|
Overall Study
STARTED
|
138
|
194
|
|
Overall Study
Treated
|
136
|
189
|
|
Overall Study
COMPLETED
|
110
|
152
|
|
Overall Study
NOT COMPLETED
|
28
|
42
|
Reasons for withdrawal
| Measure |
Placebo
Matching placebo of 2.0 mL for IA injection
|
CNTX-4975-05
Pre-filled glass syringes administered as a single 2.0 mL IA injection
|
|---|---|---|
|
Overall Study
Adverse Event
|
2
|
3
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Lack of Efficacy
|
4
|
2
|
|
Overall Study
Lost to Follow-up
|
9
|
8
|
|
Overall Study
Physician Decision
|
1
|
0
|
|
Overall Study
Protocol Violation
|
3
|
0
|
|
Overall Study
Sponsor Decision
|
2
|
0
|
|
Overall Study
Withdrawal by Subject
|
4
|
20
|
|
Overall Study
Other reasons: UNABLE TO ADMINISTER IP, COLLECT ASPIRATE
|
3
|
8
|
Baseline Characteristics
A Phase 3 Efficacy and Safety Study of Intra-articular CNTX-4975-05 (Capsaicin) vs Placebo in Subjects With OA Knee Pain
Baseline characteristics by cohort
| Measure |
Placebo
n=136 Participants
Matching placebo of 2.0 mL for IA injection
|
CNTX-4975-05
n=189 Participants
Pre-filled glass syringes administered as a single 2.0 mL IA injection
|
Total
n=325 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.8 Years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
61.8 Years
STANDARD_DEVIATION 9.1 • n=7 Participants
|
61.8 Years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
83 Participants
n=5 Participants
|
123 Participants
n=7 Participants
|
206 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
53 Participants
n=5 Participants
|
66 Participants
n=7 Participants
|
119 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
23 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
113 Participants
n=5 Participants
|
152 Participants
n=7 Participants
|
265 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
12 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
30 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
76 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
90 Participants
n=5 Participants
|
123 Participants
n=7 Participants
|
213 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Body Mass Index
|
32.07 kg/m^2
STANDARD_DEVIATION 5.801 • n=5 Participants
|
31.55 kg/m^2
STANDARD_DEVIATION 5.692 • n=7 Participants
|
31.77 kg/m^2
STANDARD_DEVIATION 5.734 • n=5 Participants
|
|
Baseline Pain with Walking NPRS (0-10) Score
|
7.09 score on a scale
STANDARD_DEVIATION 1.152 • n=5 Participants
|
7.06 score on a scale
STANDARD_DEVIATION 1.082 • n=7 Participants
|
7.07 score on a scale
STANDARD_DEVIATION 1.110 • n=5 Participants
|
|
Baseline WOMAC A (Pain) Domain Score (range 0-50)
|
30.80 score on a scale
STANDARD_DEVIATION 8.166 • n=5 Participants
|
31.92 score on a scale
STANDARD_DEVIATION 7.493 • n=7 Participants
|
31.45 score on a scale
STANDARD_DEVIATION 7.788 • n=5 Participants
|
|
Baseline WOMAC B (Stiffness) Domain Score (range 0-20)
|
13.24 score on a scale
STANDARD_DEVIATION 3.389 • n=5 Participants
|
13.28 score on a scale
STANDARD_DEVIATION 3.232 • n=7 Participants
|
13.26 score on a scale
STANDARD_DEVIATION 3.293 • n=5 Participants
|
|
Baseline WOMAC C (Function) Domain Score (range 0-170)
|
105.25 score on a scale
STANDARD_DEVIATION 29.755 • n=5 Participants
|
108.23 score on a scale
STANDARD_DEVIATION 27.085 • n=7 Participants
|
106.99 score on a scale
STANDARD_DEVIATION 28.222 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data.
Average daily OA pain in the index knee while walking was evaluated using a 0 to 10 Numerical Pain Rating Scale (NPRS) (0 = no pain and 10 = worst possible pain). 0 was the best score and 10 was the worst score. Subjects used an ePRO at bedtime (9:00 PM ± 3 hours) to record on a daily basis their average daily OA knee pain score with walking during the previous 24 hours.
Outcome measures
| Measure |
Placebo
n=130 Participants
Matching placebo of 2.0 mL for IA injection
|
CNTX-4975-05
n=177 Participants
Pre-filled glass syringes administered as a single 2.0 mL IA injection
|
|---|---|---|
|
Change From Baseline in Average Weekly Pain With Walking (NPRS 0-10) in the Index Knee
|
-2.84 score on a scale
Standard Error 0.212
|
-3.17 score on a scale
Standard Error 0.182
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data.
The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome. The pain dimension includes 5 items about the amount of pain experienced doing various activities (walking, stair climbing, nocturnal, at rest, weight bearing). The score ranges from 0 to 50.
Outcome measures
| Measure |
Placebo
n=128 Participants
Matching placebo of 2.0 mL for IA injection
|
CNTX-4975-05
n=174 Participants
Pre-filled glass syringes administered as a single 2.0 mL IA injection
|
|---|---|---|
|
Mean Change From Baseline in WOMAC A (Pain) Dimension Total Score
|
-12.72 score on a scale
Standard Error 1.002
|
-15.42 score on a scale
Standard Error 0.860
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data.
The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome. The stiffness dimension has 2 items: joint stiffness upon wakening and joint stiffness later in the day. The score ranges from 0 to 20.
Outcome measures
| Measure |
Placebo
n=128 Participants
Matching placebo of 2.0 mL for IA injection
|
CNTX-4975-05
n=174 Participants
Pre-filled glass syringes administered as a single 2.0 mL IA injection
|
|---|---|---|
|
Mean Change From Baseline WOMAC B (Stiffness) Dimension Total Score
|
-5.21 score on a scale
Standard Error 0.448
|
-6.15 score on a scale
Standard Error 0.386
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data.
The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain (Subscale A), Stiffness (Subscale B), and Physical Function (Subscale C). Lower scores mean a better outcome and higher scores mean a worse outcome. The function dimension asks about the degree of difficulty in doing 17 activities due to the reference joint. The score ranges from 0 to 170.
Outcome measures
| Measure |
Placebo
n=128 Participants
Matching placebo of 2.0 mL for IA injection
|
CNTX-4975-05
n=174 Participants
Pre-filled glass syringes administered as a single 2.0 mL IA injection
|
|---|---|---|
|
Mean Change From Baseline in WOMAC C (Physical Function) Dimension Total Score
|
-42.70 score on a scale
Standard Error 3.417
|
-50.49 score on a scale
Standard Error 2.935
|
Adverse Events
Placebo
CNTX-4975-05
Serious adverse events
| Measure |
Placebo
n=136 participants at risk
Matching placebo of 2.0 mL for IA injection
|
CNTX-4975-05
n=189 participants at risk
Pre-filled glass syringes administered as a single 2.0 mL IA injection
|
|---|---|---|
|
Injury, poisoning and procedural complications
Acetabulum Fracture
|
0.00%
0/136 • 1 Year
|
0.53%
1/189 • Number of events 1 • 1 Year
|
|
Injury, poisoning and procedural complications
Craniocerebral Injury
|
0.00%
0/136 • 1 Year
|
0.53%
1/189 • Number of events 1 • 1 Year
|
|
Injury, poisoning and procedural complications
Foot Fracture
|
0.74%
1/136 • Number of events 1 • 1 Year
|
0.00%
0/189 • 1 Year
|
|
Injury, poisoning and procedural complications
Hip Fracture
|
0.74%
1/136 • Number of events 1 • 1 Year
|
0.00%
0/189 • 1 Year
|
|
General disorders
Chest Pain
|
0.74%
1/136 • Number of events 1 • 1 Year
|
0.00%
0/189 • 1 Year
|
|
General disorders
Systemic inflammatory response
|
0.00%
0/136 • 1 Year
|
0.53%
1/189 • Number of events 1 • 1 Year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oestrogen receipt positive breast cancer
|
0.74%
1/136 • Number of events 1 • 1 Year
|
0.00%
0/189 • 1 Year
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer
|
0.74%
1/136 • Number of events 1 • 1 Year
|
0.00%
0/189 • 1 Year
|
|
Vascular disorders
Hypotension
|
0.00%
0/136 • 1 Year
|
0.53%
1/189 • Number of events 1 • 1 Year
|
|
Vascular disorders
Peripheral Ischaemia
|
0.74%
1/136 • Number of events 1 • 1 Year
|
0.00%
0/189 • 1 Year
|
|
Cardiac disorders
Supraventricular Tachycardia
|
0.00%
0/136 • 1 Year
|
0.53%
1/189 • Number of events 1 • 1 Year
|
|
Ear and labyrinth disorders
Vertigo Positional
|
0.74%
1/136 • Number of events 1 • 1 Year
|
0.00%
0/189 • 1 Year
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Failure
|
0.00%
0/136 • 1 Year
|
0.53%
1/189 • Number of events 1 • 1 Year
|
|
Respiratory, thoracic and mediastinal disorders
Branchospasm
|
0.00%
0/136 • 1 Year
|
0.53%
1/189 • Number of events 1 • 1 Year
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/136 • 1 Year
|
0.53%
1/189 • Number of events 1 • 1 Year
|
|
Surgical and medical procedures
Hip Arthroplasty
|
0.74%
1/136 • Number of events 1 • 1 Year
|
0.00%
0/189 • 1 Year
|
|
Infections and infestations
Appendicitis
|
0.00%
0/136 • 1 Year
|
0.53%
1/189 • Number of events 1 • 1 Year
|
Other adverse events
| Measure |
Placebo
n=136 participants at risk
Matching placebo of 2.0 mL for IA injection
|
CNTX-4975-05
n=189 participants at risk
Pre-filled glass syringes administered as a single 2.0 mL IA injection
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.4%
6/136 • Number of events 6 • 1 Year
|
10.1%
19/189 • Number of events 19 • 1 Year
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
2.2%
3/136 • Number of events 3 • 1 Year
|
4.2%
8/189 • Number of events 8 • 1 Year
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.5%
2/136 • Number of events 2 • 1 Year
|
2.6%
5/189 • Number of events 5 • 1 Year
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
0.74%
1/136 • Number of events 1 • 1 Year
|
2.6%
5/189 • Number of events 5 • 1 Year
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
2.2%
3/136 • Number of events 3 • 1 Year
|
1.6%
3/189 • Number of events 3 • 1 Year
|
|
Musculoskeletal and connective tissue disorders
Joint stiffness
|
0.00%
0/136 • 1 Year
|
2.1%
4/189 • Number of events 4 • 1 Year
|
|
Infections and infestations
Upper respiratory tract infection
|
5.1%
7/136 • Number of events 7 • 1 Year
|
4.2%
8/189 • Number of events 8 • 1 Year
|
|
Infections and infestations
Viral upper respiratory tract infection
|
2.2%
3/136 • Number of events 3 • 1 Year
|
2.1%
4/189 • Number of events 4 • 1 Year
|
|
Infections and infestations
Influenza
|
0.74%
1/136 • Number of events 1 • 1 Year
|
2.6%
5/189 • Number of events 5 • 1 Year
|
|
Infections and infestations
Urinary tract infection
|
2.2%
3/136 • Number of events 3 • 1 Year
|
1.6%
3/189 • Number of events 3 • 1 Year
|
|
Gastrointestinal disorders
Nausea
|
1.5%
2/136 • Number of events 2 • 1 Year
|
6.3%
12/189 • Number of events 12 • 1 Year
|
|
Injury, poisoning and procedural complications
Procedural pain
|
1.5%
2/136 • Number of events 2 • 1 Year
|
2.6%
5/189 • Number of events 5 • 1 Year
|
|
Injury, poisoning and procedural complications
Fall
|
1.5%
2/136 • Number of events 2 • 1 Year
|
2.1%
4/189 • Number of events 4 • 1 Year
|
|
Nervous system disorders
Dizziness
|
2.2%
3/136 • Number of events 3 • 1 Year
|
3.2%
6/189 • Number of events 6 • 1 Year
|
|
Nervous system disorders
Headache
|
0.74%
1/136 • Number of events 1 • 1 Year
|
2.1%
4/189 • Number of events 4 • 1 Year
|
|
General disorders
Injection site joint pain
|
0.74%
1/136 • Number of events 1 • 1 Year
|
2.1%
4/189 • Number of events 4 • 1 Year
|
|
Vascular disorders
Hypertension
|
1.5%
2/136 • Number of events 2 • 1 Year
|
2.6%
5/189 • Number of events 5 • 1 Year
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/136 • 1 Year
|
3.2%
6/189 • Number of events 6 • 1 Year
|
|
Surgical and medical procedures
Tooth extraction
|
2.2%
3/136 • Number of events 3 • 1 Year
|
0.00%
0/189 • 1 Year
|
Additional Information
Director of Clinical Operations
Centrexion Therapeutics, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place