NCT03429049

A Phase 3 Efficacy and Safety Study of Intra-articular CNTX-4975-05 (Capsaicin) vs Placebo in Subjects With OA Knee Pain

Completed Phase 3 Results posted Last updated 26 July 2022

What this trial tests

Phase 3 trial testing CNTX-4975-05 in Osteoarthritis, Knee in 332 participants. Completed in 22 November 2019.

Timeline

24 January 2018

Primary endpoint
22 November 2019

22 November 2019

Quick facts

Lead sponsor	Centrexion Therapeutics
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	332
Start date	24 January 2018
Primary completion	22 November 2019
Estimated completion	22 November 2019
Sites	33 locations across United States

Drugs / interventions tested

• CNTX-4975-05 — full drug profile →
• Placebo

Conditions studied

• Osteoarthritis, Knee — all drugs for Osteoarthritis, Knee →

Sponsor

Centrexion Therapeutics — full company profile →

Who can join

Adults 40 to 95, any sex, with Osteoarthritis, Knee. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in Average Weekly Pain With Walking (NPRS 0-10) in the Index Knee Primary · Baseline, Week 12

Average daily OA pain in the index knee while walking was evaluated using a 0 to 10 Numerical Pain Rating Scale (NPRS) (0 = no pain and 10 = worst possible pain). 0 was the best score and 10 was the worst score. Subjects used an ePRO at bedtime (9:00 PM ± 3 hours) to record on a daily basis their average daily OA knee pain score with walking during the previous 24 hours.

Group	Value	95% CI
Placebo	-2.84	± 0.212
CNTX-4975-05	-3.17	± 0.182

Mean Change From Baseline in WOMAC A (Pain) Dimension Total Score Secondary · Baseline, Week 12

The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain

Group	Value	95% CI
Placebo	-12.72	± 1.002
CNTX-4975-05	-15.42	± 0.860

Mean Change From Baseline WOMAC B (Stiffness) Dimension Total Score Secondary · Baseline, Week 12

The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain

Group	Value	95% CI
Placebo	-5.21	± 0.448
CNTX-4975-05	-6.15	± 0.386

Mean Change From Baseline in WOMAC C (Physical Function) Dimension Total Score Secondary · Baseline, Week 12

The Western Ontario and McMaster Universities developed the Western Ontario and McMaster Universities Arthritis Index (WOMAC) score to use among patients with knee and/or hip OA. The WOMAC is a validated, multidimensional measure of pain, stiffness, and physical functional disability that is sensitive to the effects of drugs or other interventions. This study used the 11-box NPRS format ranging from 0 (none or no pain/stiffness/difficulty) to 10 (extreme). The WOMAC is a self-administered index that contains 24 items asked in relation to the index knee joint. The WOMAC has 3 dimensions: Pain

Group	Value	95% CI
Placebo	-42.70	± 3.417
CNTX-4975-05	-50.49	± 2.935

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 Year. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 6/136 (4%)

Deaths: 0/136

CNTX-4975-05

Serious: 6/189 (3%)

Deaths: 1/189

Serious adverse events (17 terms)

Reaction	System	Placebo	CNTX-4975-05
Acetabulum Fracture	Injury, poisoning and procedural complications	—	—
Craniocerebral Injury	Injury, poisoning and procedural complications	—	—
Foot Fracture	Injury, poisoning and procedural complications	—	—
Hip Fracture	Injury, poisoning and procedural complications	—	—
Chest Pain	General disorders	—	—
Systemic inflammatory response	General disorders	—	—
Oestrogen receipt positive breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Prostate Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Hypotension	Vascular disorders	—	—
Peripheral Ischaemia	Vascular disorders	—	—
Supraventricular Tachycardia	Cardiac disorders	—	—
Vertigo Positional	Ear and labyrinth disorders	—	—
Acute Respiratory Failure	Respiratory, thoracic and mediastinal disorders	—	—
Branchospasm	Respiratory, thoracic and mediastinal disorders	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Hip Arthroplasty	Surgical and medical procedures	—	—
Appendicitis	Infections and infestations	—	—

Other adverse events (19 terms — click to expand)

Reaction	System	Placebo	CNTX-4975-05
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Dizziness	Nervous system disorders	—	—
Hyperhidrosis	Skin and subcutaneous tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Joint effusion	Musculoskeletal and connective tissue disorders	—	—
Influenza	Infections and infestations	—	—
Procedural pain	Injury, poisoning and procedural complications	—	—
Hypertension	Vascular disorders	—	—
Joint stiffness	Musculoskeletal and connective tissue disorders	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—
Fall	Injury, poisoning and procedural complications	—	—
Headache	Nervous system disorders	—	—
Injection site joint pain	General disorders	—	—
Joint swelling	Musculoskeletal and connective tissue disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Tooth extraction	Surgical and medical procedures	—	—

Most-reported serious reactions: Acetabulum Fracture, Craniocerebral Injury, Foot Fracture, Hip Fracture, Chest Pain, Systemic inflammatory response, Oestrogen receipt positive breast cancer, Prostate Cancer.

Data from ClinicalTrials.gov NCT03429049 adverse events section.

Sponsor's own description

This is a phase 3, randomized, double-blind, placebo-controlled, single injection, 52-week study to evaluate the analgesic efficacy and safety of a single intra-articular (IA) CNTX-4975-05 (capsaicin), compared to IA placebo, in subjects with chronic, moderate-to-severe osteoarthritis (OA) knee pain.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Phenotype Diversity of Macrophages in Osteoarthritis: Implications for Development of Macrophage Modulating Therapies.
   Mushenkova NV, Nikiforov NG, Shakhpazyan NK, Orekhova VA, et al · · 2022 · cited 34× · PMID 35955514 · DOI 10.3390/ijms23158381
2. Chondroprotective Factors in Osteoarthritis: a Joint Affair.
   Mimpen JY, Snelling SJB. · · 2019 · cited 18× · PMID 31227927 · DOI 10.1007/s11926-019-0840-y
3. Challenges and opportunities of pharmacological interventions for osteoarthritis: A review of current clinical trials and developments.
   Vrouwe JPM, Burggraaf J, Kloppenburg M, Stuurman FE. · · 2021 · cited 16× · PMID 36474768 · DOI 10.1016/j.ocarto.2021.100212
4. An update on targets for treating osteoarthritis pain: NGF and TRPV1.
   Obeidat AM, Donner A, Miller RE. · · 2020 · cited 14× · PMID 34178580 · DOI 10.1007/s40674-020-00146-x
5. Pharmaceutical therapeutics for articular regeneration and restoration: state-of-the-art technology for screening small molecular drugs.
   Chen Y, Sun H, Yao X, Yu Y, et al · · 2021 · cited 9× · PMID 34783870 · DOI 10.1007/s00018-021-03983-8
6. TRPV1 Receptor Modulators: Emerging Therapies for Neuropathic, Osteoarthritic, and Perioperative Pain.
   Tsai EH, Gan TJ. · · 2026 · PMID 41722000 · DOI 10.1007/s40263-026-01272-1