Trial Outcomes & Findings for A Clinical Study to Test Efficacy and Safety of Repeat Doses of CNTX-4975-05 in Patients With Osteoarthritis Knee Pain (NCT NCT03660943)

NCT ID: NCT03660943

Last Updated: 2022-07-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

332 participants

Primary outcome timeframe

Baseline, Week 12

Results posted on

2022-07-21

Participant Flow

Participant milestones

Participant milestones
Measure
Placebo
Matching placebo of 2.0 mL for IA injection
CNTX-4975-05 (Trans-capsaicin)
Pre-filled glass syringes administered as a single 2.0 mL IA injection
Overall Study
STARTED
145
187
Overall Study
Treated
140
184
Overall Study
COMPLETED
109
134
Overall Study
NOT COMPLETED
36
53

Reasons for withdrawal

Reasons for withdrawal
Measure
Placebo
Matching placebo of 2.0 mL for IA injection
CNTX-4975-05 (Trans-capsaicin)
Pre-filled glass syringes administered as a single 2.0 mL IA injection
Overall Study
Adverse Event
5
3
Overall Study
Death
0
2
Overall Study
Lost to Follow-up
7
3
Overall Study
Protocol Violation
3
5
Overall Study
Withdrawal by Subject
8
15
Overall Study
Lack of Efficacy
9
12
Overall Study
WITHDRAWAL FOR OTHER TREATMENT; UNABLE TO COMPLETE INJECTION PROCEDURES
4
13

Baseline Characteristics

A Clinical Study to Test Efficacy and Safety of Repeat Doses of CNTX-4975-05 in Patients With Osteoarthritis Knee Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Placebo
n=140 Participants
Matching placebo of 2.0 mL for IA injection
CNTX-4975-05 (Trans-capsaicin)
n=184 Participants
Pre-filled glass syringes administered as a single 2.0 mL IA injection
Total
n=324 Participants
Total of all reporting groups
Age, Continuous
62.8 years
STANDARD_DEVIATION 8.59 • n=5 Participants
62.8 years
STANDARD_DEVIATION 8.80 • n=7 Participants
62.8 years
STANDARD_DEVIATION 8.70 • n=5 Participants
Sex: Female, Male
Female
84 Participants
n=5 Participants
115 Participants
n=7 Participants
199 Participants
n=5 Participants
Sex: Female, Male
Male
56 Participants
n=5 Participants
69 Participants
n=7 Participants
125 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
37 Participants
n=5 Participants
56 Participants
n=7 Participants
93 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
103 Participants
n=5 Participants
128 Participants
n=7 Participants
231 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
2 Participants
n=5 Participants
2 Participants
n=7 Participants
4 Participants
n=5 Participants
Race (NIH/OMB)
Asian
2 Participants
n=5 Participants
0 Participants
n=7 Participants
2 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
37 Participants
n=5 Participants
49 Participants
n=7 Participants
86 Participants
n=5 Participants
Race (NIH/OMB)
White
97 Participants
n=5 Participants
131 Participants
n=7 Participants
228 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
n=5 Participants
2 Participants
n=7 Participants
3 Participants
n=5 Participants
Body Mass Index (kg/m^2)
32.40 kg/m^2
STANDARD_DEVIATION 5.265 • n=5 Participants
32.37 kg/m^2
STANDARD_DEVIATION 5.895 • n=7 Participants
32.38 kg/m^2
STANDARD_DEVIATION 5.623 • n=5 Participants
Study Baseline WOMAC A (Pain) Domain Score (range 0-50)
31.3 score on a scale
STANDARD_DEVIATION 7.2 • n=5 Participants
31.6 score on a scale
STANDARD_DEVIATION 7.36 • n=7 Participants
31.5 score on a scale
STANDARD_DEVIATION 7.28 • n=5 Participants
Study Baseline WOMAC B (Stiffness) Domain Score (range 0-20)
13.2 score on a scale
STANDARD_DEVIATION 3.41 • n=5 Participants
13.2 score on a scale
STANDARD_DEVIATION 3.15 • n=7 Participants
13.2 score on a scale
STANDARD_DEVIATION 3.26 • n=5 Participants
Study Baseline WOMAC C (Function) Domain Score (range 0-170)
107.9 score on a scale
STANDARD_DEVIATION 26.71 • n=5 Participants
109.5 score on a scale
STANDARD_DEVIATION 25.89 • n=7 Participants
108.8 score on a scale
STANDARD_DEVIATION 26.22 • n=5 Participants
Average Weekly Pain with Walking NPRS (0-10) Score
6.933 score on a scale
STANDARD_DEVIATION 1.021 • n=5 Participants
7.013 score on a scale
STANDARD_DEVIATION 0.9950 • n=7 Participants
6.978 score on a scale
STANDARD_DEVIATION 1.0055 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data

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

Outcome measures
Measure
Placebo
n=125 Participants
Matching placebo of 2.0 mL for IA injection
CNTX-4975-05
n=164 Participants
Pre-filled glass syringes administered as a single 2.0 mL IA injection
Mean Change From Baseline in WOMAC A (Pain) Dimension
-14.13 score on a scale
Standard Deviation 12.217
-17.16 score on a scale
Standard Deviation 12.266

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data as collected in the daily diary

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

Outcome measures
Measure
Placebo
n=128 Participants
Matching placebo of 2.0 mL for IA injection
CNTX-4975-05
n=170 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
-2.99 score on a scale
Standard Error 0.213
-3.41 score on a scale
Standard Error 0.197

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: The intent to treat (ITT) population included all randomized subjects who received any amount of investigational product and all observed data

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

Outcome measures
Measure
Placebo
n=125 Participants
Matching placebo of 2.0 mL for IA injection
CNTX-4975-05
n=164 Participants
Pre-filled glass syringes administered as a single 2.0 mL IA injection
Mean Change From Study Baseline in WOMAC B (Stiffness) Dimension
-5.36 score on a scale
Standard Error 0.434
-6.58 score on a scale
Standard Error 0.404

SECONDARY outcome

Timeframe: Baseline, Week12

Population: 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

Outcome measures
Measure
Placebo
n=125 Participants
Matching placebo of 2.0 mL for IA injection
CNTX-4975-05
n=164 Participants
Pre-filled glass syringes administered as a single 2.0 mL IA injection
Mean Change From Study Baseline in WOMAC C (Function) Dimension
-49.03 score on a scale
Standard Error 3.541
-57.02 score on a scale
Standard Error 3.307

Adverse Events

Placebo

Serious events: 9 serious events
Other events: 34 other events
Deaths: 0 deaths

CNTX-4975-05 (Trans-capsaicin)

Serious events: 9 serious events
Other events: 70 other events
Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure
Placebo
n=140 participants at risk
Matching placebo of 2.0 mL for IA injection
CNTX-4975-05 (Trans-capsaicin)
n=184 participants at risk
Pre-filled glass syringes administered as a single 2.0 mL IA injection
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
0.00%
0/140 • 1 Year
1.1%
2/184 • 1 Year
Respiratory, thoracic and mediastinal disorders
Emphysema
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Cardiac disorders
Angina unstable
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Cardiac disorders
Cardiac arrest
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Cardiac disorders
Cardiac failure congestive
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Cardiac disorders
Coronary artery disease
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Cardiac disorders
Coronary artery occlusion
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
0.71%
1/140 • 1 Year
0.54%
1/184 • 1 Year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Infections and infestations
Bronchitis
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Infections and infestations
Diverticulitis
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Infections and infestations
Peritoneal abscess
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Infections and infestations
Peritoneal bacterial
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Infections and infestations
Pneumonia
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Hepatobiliary disorders
Cholecystitis acute
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Hepatobiliary disorders
Hepatic cirrhosis
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Injury, poisoning and procedural complications
Cervical vertebral fracture
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Injury, poisoning and procedural complications
Dislocation of vertebra
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Injury, poisoning and procedural complications
Hip fracture
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Psychiatric disorders
Confusional state
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Psychiatric disorders
Panic attack
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Vascular disorders
Aortic aneurysm
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Vascular disorders
Deep vein thrombosis
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year
Gastrointestinal disorders
Diverticular perforation
0.71%
1/140 • 1 Year
0.00%
0/184 • 1 Year
Metabolism and nutrition disorders
Hyperkalaemia
0.00%
0/140 • 1 Year
0.54%
1/184 • 1 Year

Other adverse events

Other adverse events
Measure
Placebo
n=140 participants at risk
Matching placebo of 2.0 mL for IA injection
CNTX-4975-05 (Trans-capsaicin)
n=184 participants at risk
Pre-filled glass syringes administered as a single 2.0 mL IA injection
Infections and infestations
Viral upper respiratory tract infection
3.6%
5/140 • 1 Year
7.1%
13/184 • 1 Year
Infections and infestations
Upper respiratory tract infection
4.3%
6/140 • 1 Year
2.2%
4/184 • 1 Year
Infections and infestations
Bronchitis
1.4%
2/140 • 1 Year
3.3%
6/184 • 1 Year
Infections and infestations
Sinusitis
2.1%
3/140 • 1 Year
2.7%
5/184 • 1 Year
Infections and infestations
Urinary tract infection
2.1%
3/140 • 1 Year
2.2%
4/184 • 1 Year
Musculoskeletal and connective tissue disorders
Arthralgia
0.71%
1/140 • 1 Year
5.4%
10/184 • 1 Year
Musculoskeletal and connective tissue disorders
Back Pain
0.71%
1/140 • 1 Year
2.2%
4/184 • 1 Year
Musculoskeletal and connective tissue disorders
Pain in extremity
0.71%
1/140 • 1 Year
2.2%
4/184 • 1 Year
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
2.9%
4/140 • 1 Year
0.00%
0/184 • 1 Year
Musculoskeletal and connective tissue disorders
Arthritis
2.1%
3/140 • 1 Year
0.00%
0/184 • 1 Year
Injury, poisoning and procedural complications
Procedural dizziness
0.71%
1/140 • 1 Year
3.8%
7/184 • 1 Year
Nervous system disorders
Headache
2.1%
3/140 • 1 Year
2.2%
4/184 • 1 Year
Gastrointestinal disorders
Nausea
0.71%
1/140 • 1 Year
2.7%
5/184 • 1 Year
Blood and lymphatic system disorders
Anaemia
0.00%
0/140 • 1 Year
2.2%
4/184 • 1 Year

Additional Information

Director of Clinical Operations

Centrexion Therapeutics, Inc.

Phone: 617-837-6911

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place