NCT03190369: C-SOUND

Randomized Study of the Efficacy and Safety of a Single Dose of Synvisc-One® in Chinese Patients With Symptomatic Osteoarthritis of the Knee

Completed Phase 3 Results posted Last updated 25 March 2022

What this trial tests

Phase 3 trial testing Hylan G-F 20 (GZ402662/SAR402662) in Osteoarthritis in 440 participants. Completed in 28 January 2019.

Timeline

21 August 2017

Primary endpoint
28 January 2019

28 January 2019

Quick facts

Lead sponsor	Genzyme, a Sanofi Company
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	440
Start date	21 August 2017
Primary completion	28 January 2019
Estimated completion	28 January 2019
Sites	21 locations across China

Drugs / interventions tested

• Hylan G-F 20 (GZ402662/SAR402662)
• Placebo

Conditions studied

• Osteoarthritis — all drugs for Osteoarthritis →

Sponsor

Genzyme, a Sanofi Company — full company profile →

Who can join

Adults 40 to 80, any sex, with Osteoarthritis. 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 Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Pain (Walking Pain) Subscale Score Over 26 Weeks Primary · From Baseline up to Week 26

The WOMAC Numerical Rating Scale (NRS) version 3.1 questionnaire was a self-administered, health status measure questionnaire of 24 questions comprising 3 subscales (joint pain, stiffness and physical function) for participants with Osteoarthritis (OA) of the knee. WOMAC A1 pain subscale (measure of pain during walking on a flat surface) was measured on 11-point (NRS) ranging from 0 (none) to 10 (extreme), where lower score represented no pain and higher score represented extreme pain.

Group	Value	95% CI
Placebo	-2.271	± 0.110
Hylan G-F 20	-2.146	± 0.108

Change From Baseline in 7-day Average WOMAC A1 Pain (Walking Pain) Subscale Score Over 26 Weeks Secondary · From Baseline up to Week 26

The WOMAC NRS version 3.1 questionnaire was a self-administered, health status measure questionnaire of 24 questions comprising 3 subscales (joint pain, stiffness and physical function) for participants with OA of the knee. WOMAC A1 pain subscale (measure of pain during walking on a flat surface) was measured on 11-point (NRS) ranging from 0 (none) to 10 (extreme), where lower score represented no pain and higher score represented extreme pain. For 7-day average WOMAC A1, the baseline value was defined as the average of the WOMAC A1 scores recorded 7 days prior to the first investigational med

Group	Value	95% CI
Placebo	-2.275	± 0.108
Hylan G-F 20	-2.176	± 0.106

Change From Baseline in WOMAC A Score Over 26 Weeks Secondary · From Baseline up to Week 26

The WOMAC NRS version 3.1 questionnaire was a self-administered, health status measure questionnaire of 24 questions comprising 3 subscales (joint pain, stiffness and physical function) for participants with OA of the knee. WOMAC A (5 items: measure of pain while walking, using stairs, at night while in bed, sitting or lying, and standing); each item was measured on 11-point (NRS) ranging from 0 (none) to 10 (extreme), where lower score represented no pain and higher score represented extreme pain. Total WOMAC A score was the sum of 5 item scores and ranges from 0 (none) to 50 (extreme); where

Group	Value	95% CI
Placebo	-8.747	± 0.491
Hylan G-F 20	-8.621	± 0.486

Change From Baseline in Patient Global Self-Assessment (PTGA) Score of Osteoarthritis Over 26 Weeks Secondary · From Baseline up to Week 26

PTGA (self-assessment of target knee OA condition) was measured using an 11-point NRS ranging from 0 (best possible) to 10 (worst possible), where lower score represented best possible condition and higher score represented worst possible condition.

Group	Value	95% CI
Placebo	-2.138	± 0.104
Hylan G-F 20	-2.144	± 0.102

Change From Baseline in Clinical Observer Global Assessment (COGA) Score of Osteoarthritis Over 26 Weeks Secondary · From Baseline up to Week 26

COGA was used by the physicians to perform a global assessment of the participant's target knee OA condition. The response was captured using the 11-point NRS pain intensity rating scale ranging from 0 (best possible) to 10 (worst possible) at the specified time points, where lower score represented best possible condition and higher score represented worst possible condition.

Group	Value	95% CI
Placebo	-2.145	± 0.095
Hylan G-F 20	-2.225	± 0.094

Percentage of Positive WOMAC A1 Responder Over 26 Weeks Secondary · Week 4, Week 8, Week 12, Week 16, Week 20 and Week 26

WOMAC A1 responder were defined as \>=2-point improvement from baseline in the WOMAC A1 NRS. The WOMAC NRS version 3.1 questionnaire was a self-administered, health status measure questionnaire of 24 questions comprising 3 subscales (joint pain, stiffness and physical function) for participants with OA of the knee. WOMAC A1 pain subscale (measure of pain during walking on a flat surface) was measured on 11-point (NRS) ranging from 0 (none) to 10 (extreme), where lower score represented no pain and higher score represented extreme pain.

Week 4

Group	Value	95% CI
Placebo	58.6
Hylan G-F 20	53.2

Week 8

Group	Value	95% CI
Placebo	65.0
Hylan G-F 20	62.4

Week 12

Group	Value	95% CI
Placebo	66.4
Hylan G-F 20	62.8

Week 16

Group	Value	95% CI
Placebo	69.1
Hylan G-F 20	63.3

Week 20

Group	Value	95% CI
Placebo	65.0
Hylan G-F 20	66.5

Week 26

Group	Value	95% CI
Placebo	68.2
Hylan G-F 20	67.0

Number of Participants With Treatment Emergent Adverse Events (TEAEs) Secondary · From Baseline up to Week 26

Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed, worsened (according to the Investigator opinion), or became serious during the on-treatment period (time from the injection of IMP up to Week 26 follow-up visit).

Group	Value	95% CI
Placebo	142
Hylan G-F 20	134

Adverse events — posted to ClinicalTrials.gov

Time frame: AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo

Serious: 10/220 (5%)

Deaths: 0/220

Hylan G-F 20

Serious: 14/218 (6%)

Deaths: 0/218

Serious adverse events (21 terms)

Reaction	System	Placebo	Hylan G-F 20
Pneumonia	Infections and infestations	—	—
Hypertension	Vascular disorders	—	—
Bronchitis	Infections and infestations	—	—
Hepatitis B	Infections and infestations	—	—
Colon Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Lung Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Ovarian Fibroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Rectal Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Renal Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Type 2 Diabetes Mellitus	Metabolism and nutrition disorders	—	—
Cerebral Infarction	Nervous system disorders	—	—
Lacunar Infarction	Nervous system disorders	—	—
Arteriosclerosis Coronary Artery	Cardiac disorders	—	—
Abdominal Adhesions	Gastrointestinal disorders	—	—
Intervertebral Disc Protrusion	Musculoskeletal and connective tissue disorders	—	—
Lumbar Spinal Stenosis	Musculoskeletal and connective tissue disorders	—	—
Spinal Osteoarthritis	Musculoskeletal and connective tissue disorders	—	—
Uterine Polyp	Reproductive system and breast disorders	—	—
Joint Injury	Injury, poisoning and procedural complications	—	—
Ligament Sprain	Injury, poisoning and procedural complications	—	—
Radius Fracture	Injury, poisoning and procedural complications	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Placebo	Hylan G-F 20
Upper Respiratory Tract Infection	Infections and infestations	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Joint Swelling	Musculoskeletal and connective tissue disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Toothache	Gastrointestinal disorders	—	—

Most-reported serious reactions: Pneumonia, Hypertension, Bronchitis, Hepatitis B, Colon Cancer, Lung Adenocarcinoma, Ovarian Fibroma, Rectal Cancer.

Data from ClinicalTrials.gov NCT03190369 adverse events section.

Sponsor's own description

Primary Objective:

-To evaluate the efficacy of a single 6-milliliter (mL) intra-articular (IA) injection of Hylan G-F 20 measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Numerical Rating Scale (NRS) 3.1 A1 score, in comparison to an IA placebo injection over 26 weeks, in Chinese participants with symptomatic Osteoarthritis (OA) of the knee.

Secondary Objectives:

* To evaluate the efficacy of a single 6-mL IA injection of Hylan G-F 20 measured by 7-day average score of WOMAC A1 pain sub-score in comparison to an IA placebo injection over 26 weeks.
* To evaluate the efficacy of a single 6-mL IA injection of Hylan G-F 20 measured by WOMAC A, patient global assessment (PTGA) and clinical observer global assessment (COGA) in comparison to an IA placebo injection over 26 weeks.
* To evaluate the response rate of a single 6-mL IA injection of Hylan G-F 20 in comparison to an IA placebo injection over 26 weeks. Response was defined as WOMAC A1 greater than or equal to (\>=) 2-point improvement from baseline on NRS.
* To evaluate the safety of a single 6-mL IA injection of Hylan G-F 20, in comparison to an IA placebo injection over 26 weeks.

Publications & conference data

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

1. Efficacy and safety of a single intra-articular injection of 6 ml Hylan G-F 20 compared to placebo in Chinese patients with symptomatic knee osteoarthritis : C-SOUND study, a 26-week multicenter double-blind randomized placebo-controlled trial in China.
   Ke Y, Jiang W, Xu Y, Chen Y, et al · · 2021 · cited 12× · PMID 33964907 · DOI 10.1186/s12891-021-04252-2
2. The osteochondral regeneration paradox: why biomimetic scaffolds are biologically superior but injectable systems dominate the clinic.
   Gubert S, Moon H, Oliva N, Texidó R. · · 2026 · PMID 41767232 · DOI 10.1039/d5ra09529h