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Trial record 1 of 1 for:    EFC12723
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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03190369
Recruitment Status : Completed
First Posted : June 16, 2017
Results First Posted : February 5, 2020
Last Update Posted : February 6, 2020
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Osteoarthritis
Interventions Device: Hylan G-F 20 (GZ402662/SAR402662)
Drug: Placebo
Enrollment 440
Recruitment Details The study was conducted at 21 sites in China from 21 August 2017 to 28 January 2019. A total of 524 participants were screened, of which, 84 participants were screen failures. Screen failures were mainly due to inclusion criteria not met.
Pre-assignment Details A total of 440 participants were enrolled and randomized in the study. Assignment to arms was done centrally using an interactive voice response system/interactive web response system (IVRS/IWRS) in 1:1 ratio (Placebo: Hylan G-F 20).
Arm/Group Title Placebo Hylan G-F 20
Hide Arm/Group Description Participants received a single intra-articular (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.
Period Title: Overall Study
Started 220 220
Treated 220 218
Completed 219 212
Not Completed 1 8
Reason Not Completed
Poor compliance to protocol             0             1
Withdraw before treatment             1             5
Randomized but not treated             0             2
Arm/Group Title Placebo Hylan G-F 20 Total
Hide Arm/Group 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. Total of all reporting groups
Overall Number of Baseline Participants 220 220 440
Hide Baseline Analysis Population Description
Analysis was performed on randomized population which consisted of all participants with a treatment kit number allocated and recorded in IVRS/IWRS database, and regardless of whether the treatment kit was used or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 220 participants 220 participants 440 participants
61.6  (7.8) 61.5  (7.9) 61.5  (7.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 220 participants 220 participants 440 participants
Female
172
  78.2%
170
  77.3%
342
  77.7%
Male
48
  21.8%
50
  22.7%
98
  22.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 220 participants 220 participants 440 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
220
 100.0%
220
 100.0%
440
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) A1 Pain (Walking Pain) Subscale Score Over 26 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on modified Intent-To-Treat (mITT) population which included all randomized and treated participants. Participants were analyzed in the treatment group to which they were randomized.
Arm/Group Title Placebo Hylan G-F 20
Hide Arm/Group 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.
Overall Number of Participants Analyzed 220 218
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.271  (0.110) -2.146  (0.108)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Hylan G-F 20
Comments Least-square (LS) means, standard errors (SE) were analyzed from repeated measures analysis of covariance (ANCOVA). The model included treatment groups (Hylan G-F 20 and placebo), site, visit and visit by treatment interaction, as well as the baseline WOMAC A1 score as a covariate).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3610
Comments Threshold for significance at 0.05 level.
Method ANCOVA
Comments Least-square (LS) means, standard errors (SE) were analyzed from repeated measures ANCOVA.
Method of Estimation Estimation Parameter LS Mean difference
Estimated Value 0.125
Confidence Interval (2-Sided) 95%
-0.144 to 0.395
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.137
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in 7-day Average WOMAC A1 Pain (Walking Pain) Subscale Score Over 26 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Placebo Hylan G-F 20
Hide Arm/Group 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.
Overall Number of Participants Analyzed 220 218
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.275  (0.108) -2.176  (0.106)
3.Secondary Outcome
Title Change From Baseline in WOMAC A Score Over 26 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Placebo Hylan G-F 20
Hide Arm/Group 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.
Overall Number of Participants Analyzed 220 218
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-8.747  (0.491) -8.621  (0.486)
4.Secondary Outcome
Title Change From Baseline in Patient Global Self-Assessment (PTGA) Score of Osteoarthritis Over 26 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Placebo Hylan G-F 20
Hide Arm/Group 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.
Overall Number of Participants Analyzed 220 218
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.138  (0.104) -2.144  (0.102)
5.Secondary Outcome
Title Change From Baseline in Clinical Observer Global Assessment (COGA) Score of Osteoarthritis Over 26 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Placebo Hylan G-F 20
Hide Arm/Group 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.
Overall Number of Participants Analyzed 220 218
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.145  (0.095) -2.225  (0.094)
6.Secondary Outcome
Title Percentage of Positive WOMAC A1 Responder Over 26 Weeks
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population.
Arm/Group Title Placebo Hylan G-F 20
Hide Arm/Group 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.
Overall Number of Participants Analyzed 220 218
Measure Type: Number
Unit of Measure: percentage of participants
Week 4 58.6 53.2
Week 8 65.0 62.4
Week 12 66.4 62.8
Week 16 69.1 63.3
Week 20 65.0 66.5
Week 26 68.2 67.0
7.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on safety population which included randomized participants who received at least 1 injection or part of an injection of Hylan G-F 20 or placebo.
Arm/Group Title Placebo Hylan G-F 20
Hide Arm/Group 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.
Overall Number of Participants Analyzed 220 218
Measure Type: Count of Participants
Unit of Measure: Participants
142
  64.5%
134
  61.5%
Time Frame AE data was collected from the time of the injection of IMP up to Week 26 follow-up visit.
Adverse Event Reporting Description Reported AEs are TEAEs that developed, worsened, or became serious during the treatment period (time from the injection of IMP up to Week 26 follow-up visit). Analysis was performed on safety population.
 
Arm/Group Title Placebo Hylan G-F 20
Hide Arm/Group 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.
All-Cause Mortality
Placebo Hylan G-F 20
Affected / at Risk (%) Affected / at Risk (%)
Total   0/220 (0.00%)      0/218 (0.00%)    
Hide Serious Adverse Events
Placebo Hylan G-F 20
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/220 (4.55%)      14/218 (6.42%)    
Cardiac disorders     
Arteriosclerosis Coronary Artery  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Gastrointestinal disorders     
Abdominal Adhesions  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Infections and infestations     
Bronchitis  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Hepatitis B  1  1/220 (0.45%)  1 0/218 (0.00%)  0
Pneumonia  1  2/220 (0.91%)  2 2/218 (0.92%)  2
Injury, poisoning and procedural complications     
Joint Injury  1  1/220 (0.45%)  1 0/218 (0.00%)  0
Ligament Sprain  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Radius Fracture  1  1/220 (0.45%)  1 0/218 (0.00%)  0
Metabolism and nutrition disorders     
Type 2 Diabetes Mellitus  1  1/220 (0.45%)  1 0/218 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Intervertebral Disc Protrusion  1  1/220 (0.45%)  1 0/218 (0.00%)  0
Lumbar Spinal Stenosis  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Spinal Osteoarthritis  1  1/220 (0.45%)  1 1/218 (0.46%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon Cancer  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Lung Adenocarcinoma  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Ovarian Fibroma  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Rectal Cancer  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Renal Cell Carcinoma  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Nervous system disorders     
Cerebral Infarction  1  1/220 (0.45%)  1 1/218 (0.46%)  1
Lacunar Infarction  1  0/220 (0.00%)  0 1/218 (0.46%)  1
Reproductive system and breast disorders     
Uterine Polyp  1  1/220 (0.45%)  1 0/218 (0.00%)  0
Vascular disorders     
Hypertension  1  1/220 (0.45%)  1 2/218 (0.92%)  2
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Hylan G-F 20
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   66/220 (30.00%)      75/218 (34.40%)    
Gastrointestinal disorders     
Toothache  1  8/220 (3.64%)  9 11/218 (5.05%)  16
Infections and infestations     
Nasopharyngitis  1  12/220 (5.45%)  18 13/218 (5.96%)  14
Upper Respiratory Tract Infection  1  30/220 (13.64%)  40 28/218 (12.84%)  31
Musculoskeletal and connective tissue disorders     
Arthralgia  1  24/220 (10.91%)  29 26/218 (11.93%)  35
Joint Swelling  1  4/220 (1.82%)  5 16/218 (7.34%)  18
1
Term from vocabulary, MedDRA 21.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi aventis recherche & développement
Phone: 800-633-1610 ext 1#
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT03190369    
Other Study ID Numbers: EFC12723
U1111-1131-0507 ( Other Identifier: UTN )
First Submitted: June 14, 2017
First Posted: June 16, 2017
Results First Submitted: January 19, 2020
Results First Posted: February 5, 2020
Last Update Posted: February 6, 2020