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

• ClinicalTrials.gov Identifier: NCT03190369
• Recruitment Status: Completed
• First Posted: June 16, 2017
• Results First Posted: February 5, 2020
• Last Update Posted: March 25, 2022
• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Osteoarthritis	Device: Hylan G-F 20 (GZ402662/SAR402662); Drug: Placebo	Phase 3

Detailed Description:

The duration of the study was 29 weeks at maximum. The screening and wash-out period lasted for up to 14 days, depending on the half-life of the medications followed by an 8-day baseline period including the treatment day. Overall, there were up to 21 days between signing informed consent (at screening visit) and the randomization (Day 1). Treatment was administered on Day 1, and follow-up period was 26 weeks.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 440 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 26-week, Multicenter, Double-blind, Randomized, Placebo-controlled Parallel Group Study to Evaluate the Efficacy and Safety of a Single Dose of 6 mL of Hylan G-F 20 (Synvisc-One®) in Chinese Patients With Symptomatic Osteoarthritis of the Knee
• Actual Study Start Date: August 21, 2017
• Actual Primary Completion Date: January 28, 2019
• Actual Study Completion Date: January 28, 2019

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.	Drug: Placebo; Pharmaceutical form: Solution for injection Route of administration: Intra articular
Experimental: Hylan G-F 20; Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.	Device: Hylan G-F 20 (GZ402662/SAR402662); Pharmaceutical form: Solution for injection Route of administration: Intra articular; Other Name: Synvisc-One

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Pain (Walking Pain) Subscale Score Over 26 Weeks [ Time Frame: 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.

Secondary Outcome Measures :

1. Change From Baseline in 7-day Average WOMAC A1 Pain (Walking Pain) Subscale Score Over 26 Weeks [ Time Frame: 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 medicinal product (IMP) administration (WOMAC A1 score recorded on Day 1 included). The 7-day average WOMAC A1 was set as missing if 3 or more of the 7 WOMAC A1 scores were missing.
2. Change From Baseline in WOMAC A Score Over 26 Weeks [ Time Frame: 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 lower score represented no pain and higher score represented extreme pain.
3. Change From Baseline in Patient Global Self-Assessment (PTGA) Score of Osteoarthritis Over 26 Weeks [ Time Frame: 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.
4. Change From Baseline in Clinical Observer Global Assessment (COGA) Score of Osteoarthritis Over 26 Weeks [ Time Frame: 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.
5. Percentage of Positive WOMAC A1 Responder Over 26 Weeks [ Time Frame: 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.
6. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 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).

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion criteria :

• Symptomatic OA of the target knee joint with WOMAC A1 NRS score of >=4.0 and less than or equal to (<=) 8.0 as recorded in the baseline period.
• Confirmed by standard X-rays performed within 3 months prior to screening visit: modified Kellgren-Lawrence Numerical Grading System of Grade I-III in the target knee joint.
• According to the American College of Rheumatology (ACR) Criteria.
• With failure to respond adequately to conservative non-pharmacologic therapy and/or simple analgesics, such as acetaminophen.
• Participant was willing and was able to provide signed informed consent prior to any study related procedures being performed.

Exclusion criteria:

• The score of contralateral knee pain (if present) >3.0 NRS at screening visit.
• Ipsilateral hip OA.
• Participant with systemic corticosteroids within 12 weeks prior to screening visit.
• Participant with injection of IA corticosteroids in the target knee joint within 26 weeks prior to screening visit.
• Concurrent chronic pain conditions with pain score >3.0 NRS at screening, or peripheral or central neuropathy that may affect sensation of the target knee area, including but not limited to back pain, hip pain, disc herniation, sciatica, diabetic neuropathy, post-stroke pain or fibromyalgia.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

China

Investigational Site Number 1560001

Beijing, China, 100044

Investigational Site Number 1560005

Beijing, China, 100050

Investigational Site Number 1560020

Beijing, China, 100191

Investigational Site Number 1560009

Beijing, China, 100730

Investigational Site Number 1560012

Changchun, China, 130021

Investigational Site Number 1560013

Changsha, China, 410008

Investigational Site Number 1560023

Chengdu, China, 610041

Investigational Site Number 1560016

Guangzhou, China, 510080

Investigational Site Number 1560011

Hohhot, China, 010017

Investigational Site Number 1560017

Kunming, China, 650032

Investigational Site Number 1560019

Nanjing, China, 210009

Investigational Site Number 1560021

Nanjing, China, 210029

Investigational Site Number 1560007

Qingdao, China, 266003

Investigational Site Number 1560002

Shanghai, China, 200011

Investigational Site Number 1560003

Shanghai, China, 200032

Investigational Site Number 1560022

Shanghai, China, 200072

Investigational Site Number 1560018

Taiyuan, China, 030001

Investigational Site Number 1560010

Tianjin, China, 300052

Investigational Site Number 1560015

Tianjin, China, 300192

Investigational Site Number 1560006

Wuhan, China, 430033

Investigational Site Number 1560008

Wuxi, China, 214023

Sponsors and Collaborators

Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

  Study Documents (Full-Text)

Documents provided by Sanofi ( Genzyme, a Sanofi Company ):

Study Protocol  [PDF] February 17, 2017

Statistical Analysis Plan  [PDF] January 28, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ke Y, Jiang W, Xu Y, Chen Y, Zhang Q, Xue Q, Lin J, Ngai W, Nian G, Fazeli MS, Xie Y, Zhu Z. 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. BMC Musculoskelet Disord. 2021 May 8;22(1):428. doi: 10.1186/s12891-021-04252-2.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT03190369
• Other Study ID Numbers: EFC12723; U1111-1131-0507 ( Other Identifier: UTN )
• First Posted: June 16, 2017
• Results First Posted: February 5, 2020
• Last Update Posted: March 25, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Osteoarthritis; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Hylan; Viscosupplements; Protective Agents; Physiological Effects of Drugs