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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)

Primary Purpose

Osteoarthritis

Status
Completed
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Hylan G-F 20 (GZ402662/SAR402662)
Placebo
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteoarthritis

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 1560001
  • Investigational Site Number 1560005
  • Investigational Site Number 1560020
  • Investigational Site Number 1560009
  • Investigational Site Number 1560012
  • Investigational Site Number 1560013
  • Investigational Site Number 1560023
  • Investigational Site Number 1560016
  • Investigational Site Number 1560011
  • Investigational Site Number 1560017
  • Investigational Site Number 1560019
  • Investigational Site Number 1560021
  • Investigational Site Number 1560007
  • Investigational Site Number 1560002
  • Investigational Site Number 1560003
  • Investigational Site Number 1560022
  • Investigational Site Number 1560018
  • Investigational Site Number 1560010
  • Investigational Site Number 1560015
  • Investigational Site Number 1560006
  • Investigational Site Number 1560008

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Hylan G-F 20

Arm Description

Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.

Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.

Outcomes

Primary Outcome Measures

Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Pain (Walking Pain) Subscale Score Over 26 Weeks
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

Change From Baseline in 7-day Average WOMAC A1 Pain (Walking Pain) Subscale Score Over 26 Weeks
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.
Change From Baseline in WOMAC A Score Over 26 Weeks
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.
Change From Baseline in Patient Global Self-Assessment (PTGA) Score of Osteoarthritis Over 26 Weeks
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.
Change From Baseline in Clinical Observer Global Assessment (COGA) Score of Osteoarthritis Over 26 Weeks
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.
Percentage of Positive WOMAC A1 Responder Over 26 Weeks
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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
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).

Full Information

First Posted
June 14, 2017
Last Updated
March 15, 2022
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT03190369
Brief Title
Randomized Study of the Efficacy and Safety of a Single Dose of Synvisc-One® in Chinese Patients With Symptomatic Osteoarthritis of the Knee
Acronym
C-SOUND
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
August 21, 2017 (Actual)
Primary Completion Date
January 28, 2019 (Actual)
Study Completion Date
January 28, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

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
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteoarthritis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
440 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received a single IA injection of phosphate buffered saline on Day 1 and were observed for 26 weeks.
Arm Title
Hylan G-F 20
Arm Type
Experimental
Arm Description
Participants received a single IA injection of 6 mL Hylan G-F 20 (Synvisc-One) on Day 1 and were observed for 26 weeks.
Intervention Type
Device
Intervention Name(s)
Hylan G-F 20 (GZ402662/SAR402662)
Other Intervention Name(s)
Synvisc-One
Intervention Description
Pharmaceutical form: Solution for injection Route of administration: Intra articular
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form: Solution for injection Route of administration: Intra articular
Primary Outcome Measure Information:
Title
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Pain (Walking Pain) Subscale Score Over 26 Weeks
Description
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.
Time Frame
From Baseline up to Week 26
Secondary Outcome Measure Information:
Title
Change From Baseline in 7-day Average WOMAC A1 Pain (Walking Pain) Subscale Score Over 26 Weeks
Description
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.
Time Frame
From Baseline up to Week 26
Title
Change From Baseline in WOMAC A Score Over 26 Weeks
Description
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.
Time Frame
From Baseline up to Week 26
Title
Change From Baseline in Patient Global Self-Assessment (PTGA) Score of Osteoarthritis Over 26 Weeks
Description
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.
Time Frame
From Baseline up to Week 26
Title
Change From Baseline in Clinical Observer Global Assessment (COGA) Score of Osteoarthritis Over 26 Weeks
Description
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.
Time Frame
From Baseline up to Week 26
Title
Percentage of Positive WOMAC A1 Responder Over 26 Weeks
Description
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.
Time Frame
Week 4, Week 8, Week 12, Week 16, Week 20 and Week 26
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
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).
Time Frame
From Baseline up to Week 26

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 1560001
City
Beijing
ZIP/Postal Code
100044
Country
China
Facility Name
Investigational Site Number 1560005
City
Beijing
ZIP/Postal Code
100050
Country
China
Facility Name
Investigational Site Number 1560020
City
Beijing
ZIP/Postal Code
100191
Country
China
Facility Name
Investigational Site Number 1560009
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Investigational Site Number 1560012
City
Changchun
ZIP/Postal Code
130021
Country
China
Facility Name
Investigational Site Number 1560013
City
Changsha
ZIP/Postal Code
410008
Country
China
Facility Name
Investigational Site Number 1560023
City
Chengdu
ZIP/Postal Code
610041
Country
China
Facility Name
Investigational Site Number 1560016
City
Guangzhou
ZIP/Postal Code
510080
Country
China
Facility Name
Investigational Site Number 1560011
City
Hohhot
ZIP/Postal Code
010017
Country
China
Facility Name
Investigational Site Number 1560017
City
Kunming
ZIP/Postal Code
650032
Country
China
Facility Name
Investigational Site Number 1560019
City
Nanjing
ZIP/Postal Code
210009
Country
China
Facility Name
Investigational Site Number 1560021
City
Nanjing
ZIP/Postal Code
210029
Country
China
Facility Name
Investigational Site Number 1560007
City
Qingdao
ZIP/Postal Code
266003
Country
China
Facility Name
Investigational Site Number 1560002
City
Shanghai
ZIP/Postal Code
200011
Country
China
Facility Name
Investigational Site Number 1560003
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Investigational Site Number 1560022
City
Shanghai
ZIP/Postal Code
200072
Country
China
Facility Name
Investigational Site Number 1560018
City
Taiyuan
ZIP/Postal Code
030001
Country
China
Facility Name
Investigational Site Number 1560010
City
Tianjin
ZIP/Postal Code
300052
Country
China
Facility Name
Investigational Site Number 1560015
City
Tianjin
ZIP/Postal Code
300192
Country
China
Facility Name
Investigational Site Number 1560006
City
Wuhan
ZIP/Postal Code
430033
Country
China
Facility Name
Investigational Site Number 1560008
City
Wuxi
ZIP/Postal Code
214023
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
Citations:
PubMed Identifier
33964907
Citation
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.
Results Reference
derived

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

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